Scientists extract genetic secrets from 4,000-year-old teeth to illuminate the impact of changing human diets over the centuries

Researchers at Trinity College Dublin have recovered remarkably preserved microbiomes from two teeth dating back 4,000 years, found in an Irish limestone cave. Genetic analyses of these microbiomes reveal major changes in the oral microenvironment from the Bronze Age to today. The teeth both belonged to the same male individual and also provided a snapshot of his oral health.

The study, carried out in collaboration with archaeologists from the Atlantic Technological University and University of Edinburgh, was published today in journal Molecular Biology and Evolution. The authors identified several bacteria linked to gum disease and provided the first high-quality ancient genome of Streptococcus mutans, the major culprit behind tooth decay.

While S. mutans is very common in modern mouths, it is exceptionally rare in the ancient genomic record. One reason for this may be the acid-producing nature of the species. This acid decays the tooth, but also destroys DNA and stops plaque from fossilising. While most ancient oral microbiomes are retrieved from fossilised plaque, this study targeted the tooth directly.

Another reason for the scarcity of S. mutans in ancient mouths may be the lack of favorable habitats for this sugar-loving species. An uptick of dental cavities is seen in the archaeological record after the adoption of cereal agriculture thousands of years ago, but a far more dramatic increase has occurred only in the past few hundred years when sugary foods were introduced to the masses.

The sampled teeth were part of a larger skeletal assemblage excavated from Killuragh Cave, County Limerick, by the late Peter Woodman of University College Cork. While other teeth in the cave showed advanced dental decay, no cavities were visible on the sampled teeth. However, one tooth produced an unprecedented amount of S. mutans DNA, a sign of an extreme imbalance in the oral microbial community.

"We were very surprised to see such a large abundance of S. mutans in this 4,000-year-old tooth," said Dr Lara Cassidy, an assistant professor in Trinity's School of Genetics and Microbiology, and senior author of the study. "It is a remarkably rare find and suggests this man was at a high risk of developing cavities right before his death."

The researchers also found that other streptococcal species were virtually absent from the tooth. This indicates the natural balance of the oral biofilm had been upset -- mutans had outcompeted the other streptococci leading to the pre-disease state.

The team also found evidence to support the "disappearing microbiome" hypothesis, which proposes modern microbiomes are less diverse than those of our ancestors. This is cause for concern, as biodiversity loss can impact human health. The two Bronze Age teeth produced highly divergent strains of Tannerella forsythia, a bacteria implicated in gum disease.

"These strains from a single ancient mouth were more genetically different from one another than any pair of modern strains in our dataset, despite the modern samples deriving from Europe, Japan and the USA," explained Iseult Jackson, a PhD candidate at Trinity, and first author of the study. "This represents a major loss in diversity and one that we need to understand better."

Very few full genomes from oral bacteria have been recovered prior to the Medieval era. By characterising prehistoric diversity, the authors were able to reveal dramatic changes in the oral microenvironment that have happened since.

Dr Cassidy added: "Over the last 750 years, a single lineage of T. forsythia has become dominant worldwide. This is the tell-tale sign of natural selection, where one strain rises rapidly in frequency due to some genetic advantage it holds over the others. T. forsythia strains from the industrial era onwards contain many new genes that help the bacteria colonise the mouth and cause disease.

"S. mutans has also undergone recent lineage expansions and changes in gene content related to pathogenicity. These coincide with humanity's mass consumption of sugar, although we did find that modern S. mutans populations have remained more diverse, with deep splits in the S. mutans evolutionary tree pre-dating the Killuragh genome."

The scientists believe this is driven by differences in the evolutionary mechanisms that shape genome diversity in these species.

"S. mutans is very adept at swapping genetic material between strains," said Dr Cassidy. "This means an advantageous innovation can be spread across S. mutans lineages like a new piece of tech. This ability to easily share innovations may explain why this species retains many diverse lineages without one becoming dominant and replacing all the others."

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Researchers discover potential microbiome links to skin aging

The effects of aging and external factors like UV exposure on skin are well documented. As people age or spend more time in the sun, their skin tends to become drier and more wrinkled,

Recent findings have identified an exciting potential new link to signs of skin aging -- the skin microbiome, the collection of microorganisms that inhabits our skin. The results come from a collaborative study carried out by researchers at the Center for Microbiome Innovation (CMI) at the University of California San Diego (UC San Diego) and L'Oréal Research and Innovation.

Their work was published in Frontiers in Aging on January 11, 2024, in an article entitled "A multi-study analysis enables identification of potential microbial features associated with skin aging signs." To the best of the team's knowledge, the study is the first to isolate microbes associated specifically with signs of skin aging and skin health, rather than chronological age.

Combining CMI's sophisticated data analysis abilities with L'Oréal's knowledge and expertise in skin health assessment, the study comprehensively examined data collected during 13 studies that L'Oréal had carried out in the past, consisting of 16S rRNA amplicon sequence data and corresponding skin clinical data for over 650 female participants, aged 18 -- 70. While each of the studies included in the analysis had focused on one particular area of interest -- for example, crow's feet wrinkles or moisture loss -- this multi-study analysis collated the data to search for trends related to specific microbes while accounting for other variables, such as age.

"Previous studies have shown that the types of microbes on our skin change fairly predictably with age," said corresponding author Se Jin Song, the CMI Director of Research. "Our skin also changes physiologically with age; for example, we gain wrinkles and our skin gets drier. But there is variation in what this looks like in people -- you've probably noticed that there are some people who have younger or older looking skin than many others their age. Using advanced statistical methods, we were able to tease apart the microbes that are associated with these types of aging signs for skin, like crow's feet wrinkles, from those that are associated with simply age as a chronological number."

Two notable trends emerged from the analysis. First, the team found a positive association between skin microbiome diversity and lateral cantonal lines (crow's feet wrinkles), which are generally viewed as one of the key signs of skin aging. Second, they observed a negative correlation between microbiome diversity and transepidermal water loss, which is the amount of moisture that evaporates through the skin. In further exploring the trends, the researchers identified several potential biomarkers that warrant investigation as microorganisms of interest. It would be premature to infer causation or actionable insights, but the study's results have provided researchers with directions on the next steps to hone in on better understanding microbial associations with skin aging.

"At L'Oréal, our commitment is to create beauty products that meet the unique needs of each individual. Our recent collaboration with the Center for Microbiome Innovation has shed light on the role of the skin microbiome in aging, particularly in how it affects wrinkles and overall skin quality," said co-author Qian Zheng, Head of Advanced Research, North America at L'Oréal. "This research is groundbreaking in identifying new microbial biomarkers linked to visible signs of aging like crow's feet wrinkles. It marks a significant step towards developing technologies for healthier, more youthful skin. We look forward to sharing new results as they become available, furthering the scientific community's understanding and contributing to advancing new skincare solutions."

Future paths of investigation the team has suggested include metabolomics work to discover chemical biomarkers related to skin aging, as well as meta-transcriptomics research into potential targets for genetic engineering. Research into other layers of the skin has also been considered, as many studies focus on the outer skin due to the ease of sample collection.

"While the study's findings represent an advance of our knowledge of the skin microbiome, we view them as just the beginning of a new phase of research," said co-author Rob Knight, the CMI Faculty Director and Professor of Pediatrics, Bioengineering, Computer Science & Engineering and Data Science at UC San Diego. "By confirming a link between the microbiome and skin health, we've laid the groundwork for further studies that discover specific microbiome biomarkers related to skin aging, and, one day, show how to modify them to generate novel and highly targeted recommendations for skin health."

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Scientists engineer plant microbiome to protect crops against disease

Breakthrough could dramatically cut the use of pesticides and unlock other opportunities to bolster plant health

Scientists have engineered the microbiome of plants for the first time, boosting the prevalence of 'good' bacteria that protect the plant from disease.

The findings published in Nature Communications by researchers from the University of Southampton, China and Austria, could substantially reduce the need for environmentally destructive pesticides.

There is growing public awareness about the significance of our microbiome -- the myriad of microorganisms that live in and around our bodies, most notably in our guts.

Our gut microbiomes influence our metabolism, our likelihood of getting ill, our immune system, and even our mood.

Plants too host a huge variety of bacteria, fungi, viruses, and other microorganisms that live in their roots, stems, and leaves.

For the past decade, scientists have been intensively researching plant microbiomes to understand how they affect a plant's health and its vulnerability to disease.

"For the first time, we've been able to change the makeup of a plant's microbiome in a targeted way, boosting the numbers of beneficial bacteria that can protect the plant from other, harmful bacteria," says Dr Tomislav Cernava, co-author of the paper and Associate Professor in Plant-Microbe Interactions at the University of Southampton.

"This breakthrough could reduce reliance on pesticides, which are harmful to the environment. We've achieved this in rice crops, but the framework we've created could be applied to other plants and unlock other opportunities to improve their microbiome. For example, microbes that increase nutrient provision to crops could reduce the need for synthetic fertilisers."

The international research team discovered that one specific gene found in the lignin biosynthesis cluster of the rice plant is involved in shaping its microbiome.

Lignin is a complex polymer found in the cell walls of plants -- the biomass of some plant species consists of more than 30 per cent lignin.

First, the researchers observed that when this gene was deactivated, there was a decrease in the population of certain beneficial bacteria, confirming its importance in the makeup of the microbiome community.

The researchers then did the opposite, over-expressing the gene so it produced more of one specific type of metabolite -- a small molecule produced by the host plant during its metabolic processes.

This increased the proportion of beneficial bacteria in the plant microbiome.

When these engineered plants were exposed to Xanthomonas oryzae -- a pathogen that causes bacterial blight in rice crops, they were substantially more resistant to it than wild-type rice.

Bacterial blight is common in Asia and can lead to substantial loss of rice yields.

It's usually controlled by deploying polluting pesticides, so producing a crop with a protective microbiome could help bolster food security and help the environment.

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Common origin behind major childhood allergies

Several major childhood allergies may all stem from the community of bacteria living in our gut, according to a new study led by researchers at the University of British Columbia and BC Children's Hospital.

The research, published in Nature Communications, identifies gut microbiome features and early life influences that are associated with children developing any of four common allergies -- eczema, asthma, food allergy and/or hay fever. The findings could lead to methods of predicting whether a child will develop allergies, and ways to prevent them from developing at all.

"We're seeing more and more children and families seeking help at the emergency department due to allergies," said Dr. Stuart Turvey, professor in the department of pediatrics at UBC and an investigator at BC Children's Hospital Research Institute, and co-senior author on the study. "Hundreds of millions of children worldwide suffer from allergies, including one in three children in Canada, and it's important to understand why this is happening and how it can be prevented."

The study is one of the first to examine four distinct school-aged pediatric allergies at once. While these allergic diseases each have unique symptoms, the Turvey lab was curious whether they might have a common origin linked to the infant gut microbiota composition.

"These are technically different diagnoses, each with their own list of symptoms, so most researchers tend to study them individually," says Dr. Charisse Petersen, co-senior author on the paper and postdoctoral fellow in the Turvey lab. "But when you look at what is going wrong at a cellular level, they actually have a lot in common."

For the study, researchers examined clinical assessments from 1,115 children who were tracked from birth to age five. Roughly half of the children (523) had no evidence of allergies at any time, while more than half (592) were diagnosed with one or more allergic disorders by an expert physician. The researchers evaluated the children's microbiomes from stool samples collected at clinical visits at three months and one year of age.

The stool samples revealed a bacterial signature that was associated with the children developing any of the four allergies by five years of age. The bacterial signature is a hallmark of dysbiosis, or an imbalanced gut microbiota, that likely resulted in a compromised intestinal lining and an elevated inflammatory response within the gut.

"Typically, our bodies tolerate the millions of bacteria living in our guts because they do so many good things for our health. Some of the ways we tolerate them are by keeping a strong barrier between them and our immune cells and by limiting inflammatory signals that would call those immune cells into action," says Courtney Hoskinson, a PhD candidate at UBC and first author on the paper. "We found a common breakdown in these mechanisms in babies prior to the development of allergies."

Many factors can shape the infant gut microbiota, including diet, how we are born, where we live, and our exposure to antibiotics. For example, antibiotics may wipe out sensitive bacteria, while breastfeeding tends to replenish and provide necessary food for bacteria in the infant gut. The researchers examined how these types of influences affected the balance of gut microbiota and the development of allergies.

"There are a lot of potential insights from this robust analysis," says Dr. Turvey. "From these data we can see that factors such as antibiotic usage in the first year of life are more likely to result in later allergic disorders, while breastfeeding for the first six months is protective. This was universal to all the allergic disorders we studied."

Now the researchers hope to leverage the findings to inform treatments that correct an imbalanced gut microbiota and could potentially prevent allergies from developing.

"Developing therapies that change these interactions during infancy may therefore prevent the development of all sorts of allergic diseases in childhood, which often last a lifetime," says Dr. Turvey.

The research is part of the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study that recruited families through BC Children's Hospital and BC Women's Hospital + Health Centre and other pediatric hospitals across Canada. Since launching in 2008, the team of Canadian researchers has tracked the health, growth and environments of kids from birth and made important discoveries about how asthma and allergies develop.

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Hibernating corals and the microbiomes that sustain them

As winter approaches, many species of animals -- from bears and squirrels to parasitic wasps and a few lucky humans -- hunker down for some needed rest. The northern star coral (Astrangia poculata)also enters a hibernating state of dormancy, or quiescence, during this time. But what happens to its microbiome while it's sleeping?

A study led by University of California, Davis, Assistant Professor Anya Brown found that microbial communities shift while this coral enters dormancy, providing it an important seasonal reset. The work may carry implications for coral in warmer waters struggling with climate change and other environmental issues.

"Dormancy, at its most basic, is a response to an environmental stressor -- in this case, cold stress," said Brown, who is part of the UC Davis Bodega Marine Laboratory in the Department of Evolution and Ecology. "If we understand more about this recovery period, it might help us understand what microbes may be responsible for recovering coral in warmer tropical systems."

The study, published in the journal Applied and Environmental Microbiology with scientists from Woods Hole Oceanographic Institution, or WHOI, and Roger Williams University, is the first to demonstrate a persistent microbial community shift with dormancy in a marine animal.

"This study shows that microbes respond to stress and recover in a predictable pattern," said co-author Amy Apprill, an associate scientist at WHOI. "It's foundational knowledge that may help us develop probiotics or other microbial treatments for stressed tropical corals."

While you were sleeping

From October 2020 through March 2021, researchers dove 60 feet down into cold, nearly 40 degrees Fahrenheit water to collect 10 distinct colonies of the coral A. poculata from a dock in Woods Hole, Massachusetts. This coral is found in Atlantic waters extending from the Gulf of Mexico to Massachusetts. As water temperatures cool, the coral retracts its tentacles, stops eating or responding to touch, and goes dormant.

The scientists characterized the microbiomes of the wild coral before, during and after dormancy. They found that while the coral "sleeps," its microbiome sheds nutrient-loving and pathogen-associated microbes, while increasing microbes that may contribute nitrogen while the coral is no longer eating. The scientists found that this restructuring helps the corals maintain their microbial community structure.

"We have long hypothesized that Astrangia's seasonal dormancy allows the coral microbiome to reset and restructure," said co-author Koty Sharp, associate professor at Roger Williams University. "Our research found evidence for a shuffling during that dormant period that may help us identify microbial associates that are key to coral health and recovery from disturbance."

Why does coral wake up?

With this study, a marine species -- the coral A. poculata -- now joins bears, squirrels, crickets and others on the list of animals found to have microbiomes that shift while they are dormant. For example, the ground squirrel's gut microbiome plays an important role in nitrogen recycling while the squirrel fasts during hibernation.

"This work opens a lot of questions," Brown said. "A big one is: Why does the coral 'wake up' in the early spring? This study suggests that key microbial groups may play an important role in triggering the onset of or emergence from this coral's dormancy and the regulation of its microbiome."

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People with similar faces likely have similar DNA

A collection of photos of genetically unrelated lookalikes, along with DNA analysis, revealed that strong facial similarity is associated with shared genetic variants. The work appears August 23rd in the journal Cell Reports.

"Our study provides a rare insight into human likeness by showing that people with extreme lookalike faces share common genotypes, whereas they are discordant at the epigenome and microbiome levels," says senior author Manel Esteller of the Josep Carreras Leukaemia Research Institute in Barcelona, Spain. "Genomics clusters them together, and the rest sets them apart."

The number of people identified online as virtual twins or doubles who are genetically unrelated has increased due to the expansion of the World Wide Web and the possibility of exchanging pictures of humans across the planet. In the new study, Esteller and his team set out to characterize, on a molecular level, random human beings that objectively share facial features.

To do so, they recruited human doubles from the photographic work of François Brunelle, a Canadian artist who has been obtaining worldwide pictures of lookalikes since 1999. They obtained headshot pictures of 32 lookalike couples. The researchers determined an objective measure of likeness for the pairs using three different facial recognition algorithms.

In addition, the participants completed a comprehensive biometric and lifestyle questionnaire and provided saliva DNA for multiomics analysis. "This unique set of samples has allowed us to study how genomics, epigenomics, and microbiomics can contribute to human resemblance," Esteller says.

Overall, the results revealed that these individuals share similar genotypes, but differ in their DNA methylation and microbiome landscapes. Half of the lookalike pairs were clustered together by all three algorithms. Genetic analysis revealed that 9 of these 16 pairs clustered together, based on 19,277 common single-nucleotide polymorphisms.

Moreover, physical traits such as weight and height, as well as behavioral traits such as smoking and education, were correlated in lookalike pairs. Taken together, the results suggest that shared genetic variation not only relates to similar physical appearance, but may also influence common habits and behavior.

"We provided a unique insight into the molecular characteristics that potentially influence the construction of the human face," Esteller says. "We suggest that these same determinants correlate with both physical and behavioral attributes that constitute human beings."

A few study limitations include the small sample size, the use of 2D black-and-white images, and the predominance of European participants. Despite these caveats, the findings may provide a molecular basis for future applications in various fields such as biomedicine, evolution, and forensics.

"These results will have future implications in forensic medicine -- reconstructing the criminal's face from DNA -- and in genetic diagnosis -- the photo of the patient's face will already give you clues as to which genome he or she has," Esteller says. "Through collaborative efforts, the ultimate challenge would be to predict the human face structure based on the individual's multiomics landscape."

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Non-nutritive sweeteners affect human microbiomes and can alter glycemic responses

Since the late 1800s non-nutritive sweeteners have promised to deliver all the sweetness of sugar with none of the calories. They have long been believed to have no effect on the human body, but researchers publishing in the journal Cell on August 19 challenge this notion by finding that these sugar substitutes are not inert, and, in fact, some can alter human consumers' microbiomes in a way that can change their blood sugar levels.

In 2014, senior author Eran Elinav an immunologist and microbiome researcher at the Weizmann Institute of Science and the German National Cancer Center (DKFZ) and his team found that non-nutritive sweeteners affected the microbiomes of mice in ways that could impact their glycemic responses. The team was interested in whether these results would also be found in humans.

To address this important question, the research team carefully screened over 1300 individuals for those who strictly avoid non-nutritive sweeteners in their day-to-day lives, and identified a cohort of 120 individuals. These participants were broken into six groups: two controls and four who ingested well below the FDA daily allowances of either aspartame, saccharin, stevia, or sucralose.

"In subjects consuming the non-nutritive sweeteners, we could identify very distinct changes in the composition and function of gut microbes, and the molecules they secret into peripheral blood. This seemed to suggest that gut microbes in the human body are rather responsive to each of these sweeteners," says Elinav. "When we looked at consumers of non-nutritive sweeteners as groups, we found that two of the non-nutritive sweeteners, saccharin and sucralose, significantly impacted glucose tolerance in healthy adults. Interestingly, changes in the microbes were highly correlated with the alterations noted in people's glycemic responses."

To establish causation, the researchers transferred microbial samples from the study subjects to germ-free mice -- mice that have been raised in completely sterile conditions and have no microbiome of their own.

"The results were quite striking," says Elinav. "In all of the non-nutritive sweetener groups, but in none of the controls, when we transferred into these sterile mice the microbiome of the top responder individuals collected at a time point in which they were consuming the respective non-nutritive sweeteners, the recipient mice developed glycemic alterations that very significantly mirrored those of the donor individuals. In contrast, the bottom responders' microbiomes were mostly unable to elicit such glycemic responses," he adds. "These results suggest that the microbiome changes in response to human consumption of non-nutritive sweetener may, at times, induce glycemic changes in consumers in a highly personalized manner."

Elinav says that he expects the effects of the sweeteners will vary person to person because of the incredibly unique composition of our microbiome. "We need to raise awareness of the fact that non-nutritive sweeteners are not inert to the human body as we originally believed. With that said, the clinical health implications of the changes they may elicit in humans remain unknown and merit future long-term studies."

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Age and aging have critical effects on the gut microbiome

Researchers at Cedars-Sinai have found that aging produces significant changes in the microbiome of the human small intestine distinct from those caused by medications or illness burden. The findings have been published in the journal Cell Reports.

"By teasing out the microbial changes that occur in the small bowel with age, medication use and diseases, we hope to identify unique components of the microbial community to target for therapeutics and interventions that could promote healthy aging," said Ruchi Mathur, MD, the study's principal investigator.

Research exploring the gut microbiome, and its impact on health, has relied predominantly on fecal samples, which do not represent the entire gut, according to Mathur. In their study, investigators from Cedars-Sinai's Medically Associated Science and Technology (MAST) Program analyzed samples from the small intestine-which is over 20 feet in length and has the surface area of a tennis court-for examination of the microbiome and its relationship with aging.

"This study is the first of its kind to examine the microbial composition of the small intestine of subjects 18 years of age to 80. We now know that certain microbial populations are influenced more by medications, while others are more affected by certain diseases. We have identified specific microbes that appear to be only influenced by the chronological age of the person," said Mathur, an endocrinologist and director of the Diabetes Outpatient Treatment & Education Center.

The 21st century has been referred to as the "era of the gut microbiome" as scientists turn considerable attention to the role trillions of gut bacteria, fungi and viruses may play in human health and disease. The microbiome is the name given to the genes that live in these cells. Studies have suggested that disturbances in the constellations of the microbial universe may lead to critical illnesses, including gastroenterological diseases, diabetes, obesity, and some neurological disorders.

While researchers know that microbial diversity in stool decreases with age, Cedars-Sinai investigators identified bacteria in the small bowel they refer to as "disruptors" that increase and could be troublesome.

"Coliforms are normal residents of the intestine. We found that when these rod-shaped microbes become too abundant in the small bowel-as they do as we get older-they exert a negative influence on the rest of the microbial population. They are like weeds in a garden," said study co-author Gabriela Leite, PhD.

Investigators also found that as people age, the bacteria in the small intestine change from microbes that prefer oxygen to those that can survive with less oxygen, something they hope to understand as the research continues.

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Gut bacteria influence brain development

Extremely premature infants are at a high risk for brain damage. Researchers have now found possible targets for the early treatment of such damage outside the brain: Bacteria in the gut of premature infants may play a key role. The research team found that the overgrowth of the gastrointestinal tract with the bacterium Klebsiella is associated with an increased presence of certain immune cells and the development of neurological damage in premature babies.

Complex interplay: the gut-immune-brain axis

The early development of the gut, the brain and the immune system are closely interrelated. Researchers refer to this as the gut-immune-brain axis. Bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve as well as via the immune system. "We investigated the role this axis plays in the brain development of extreme preterm infants," says the first author of the study, David Seki. "The microorganisms of the gut microbiome -- which is a vital collection of hundreds of species of bacteria, fungi, viruses and other microbes -- are in equilibrium in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain," explains the microbiologist and immunologist.

Patterns in the microbiome provide clues to brain damage

"In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury," adds David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as Operational Director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna. "Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided."

Comprehensive study of the development of extremely premature infants

Starting points for the development of appropriate therapies are provided by the biomarkers that the interdisciplinary team was able to identify. "Our data show that excessive growth of the bacterium Klebsiella and the associated elevated ??-T-cell levels can apparently exacerbate brain damage," explains Lukas Wisgrill, Neonatologist from the Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics at the Department of Pediatric and Adolescent Medicine at the Medical University of Vienna. "We were able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system and the brain develop and how they interact in this process," he adds. The study monitored a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods -- the team examined the microbiome using 16S rRNA gene sequencing, among other methods -- the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants' brains.

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Fasting may help ward off infections, study in mice suggests

Fasting before and during exposure to Salmonella enterica bacteria protects mice from developing a full-blown infection, in part due to changes in the animals' gut microbiomes,according to new research published in PLOS Pathogens by Bruce Vallance and colleagues at University of British Columbia, Canada.

When people or animals develop an infection, they often lose their appetite. However it remains controversial whether fasting protects a host from infection, or increases their susceptibility. In the new study, mice were fasted for 48 hours before and during oral infection with the bacteria Salmonella enterica serovar Typhimurium, a common cause of foodborne illness in people.

Fasting decreased the signs of bacterial infection compared to fed mice, including nearly eliminating all intestinal tissue damage and inflammation. When fasted animals were re-fed for a day after their fast, there was a dramatic increase in Salmonella numbers and invasion into the intestinal walls, although the associated inflammation was still attenuated compared to normal. The results did not hold true when mice were exposed to Salmonella intravenously instead of orally, and analyses of the microbiomes of mice showed significant changes associated with fasting and protection against infection. Moreover, fasting did not fully protect germ-free mice -- bred to lack a normal microbiome -- from Salmonella, suggesting that some of the protection was due to fasting's effect on the microbiome. Experiments using the bacteria Campylobacter jejuni confirmed that the effect of fasting was not limited to Salmonella, with similar results seen.

"These data suggest that therapeutic fasting or calorie restriction has the potential to beneficially modulate infectious and potentially non-infectious gastrointestinal diseases," the researchers conclude.

The researchers add, "Our research highlights the important role that food plays in regulating interactions between the host, enteric pathogens and the gut microbiome. When food is limited, the microbiome appears to sequester the nutrients that remain, preventing pathogens from acquiring the energy they need to infect the host. While more research is needed, fasting or otherwise adjusting food intake could be exploited therapeutically to modulate infectious diseases in the future."

From Science Daily

Bacteria may aid anti-cancer immune response

 Cancer immunotherapy may get a boost from an unexpected direction: bacteria residing within tumor cells. In a new study published in Nature, researchers at the Weizmann Institute of Science and their collaborators have discovered that the immune system "sees" these bacteria and shown they can be harnessed to provoke an immune reaction against the tumor. The study may also help clarify the connection between immunotherapy and the gut microbiome, explaining the findings of previous research that the microbiome affects the success of immunotherapy.

Immunotherapy treatments of the past decade or so have dramatically improved recovery rates from certain cancers, particularly malignant melanoma; but in melanoma, they still work in only about 40% of the cases. Prof. Yardena Samuels of Weizmann's Molecular Cell Biology Department studies molecular "signposts" -- protein fragments, or peptides, on the cell surface -- that mark cancer cells as foreign and may therefore serve as potential added targets for immunotherapy. In the new study, she and colleagues extended their search for new cancer signposts to those bacteria known to colonize tumors.

Using methods developed by departmental colleague Dr. Ravid Straussman, who was one of the first to reveal the nature of the bacterial "guests" in cancer cells, Samuels and her team, led by Dr. Shelly Kalaora and Adi Nagler (joint co-first authors), analyzed tissue samples from 17 metastatic melanoma tumors derived from nine patients. They obtained bacterial genomic profiles of these tumors and then applied an approach known as HLA-peptidomics to identify tumor peptides that can be recognized by the immune system.

The research was conducted in collaboration with Dr. Jennifer A. Wargo of the University of Texas MD Anderson Cancer Center, Houston, Texas; Prof Scott N. Peterson of Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California; Prof Eytan Ruppin of the National Cancer Institute, USA; Prof Arie Admon of the Technion -- Israel Institute of Technology and other scientists.

The HLA peptidomics analysis revealed nearly 300 peptides from 41 different bacteria on the surface of the melanoma cells. The crucial new finding was that the peptides were displayed on the cancer cell surfaces by HLA protein complexes -- complexes that are present on the membranes of all cells in our body and play a role in regulating the immune response. One of the HLA's jobs is to sound an alarm about anything that's foreign by "presenting" foreign peptides to the immune system so that immune T cells can "see" them. "Using HLA peptidomics, we were able to reveal the HLA-presented peptides of the tumor in an unbiased manner," Kalaora says. "This method has already enabled us in the past to identify tumor antigens that have shown promising results in clinical trials."

It's unclear why cancer cells should perform a seemingly suicidal act of this sort: presenting bacterial peptides to the immune system, which can respond by destroying these cells. But whatever the reason, the fact that malignant cells do display these peptides in such a manner reveals an entirely new type of interaction between the immune system and the tumor.

This revelation supplies a potential explanation for how the gut microbiome affects immunotherapy. Some of the bacteria the team identified were known gut microbes. The presentation of the bacterial peptides on the surface of tumor cells is likely to play a role in the immune response, and future studies may establish which bacterial peptides enhance that immune response, enabling physicians to predict the success of immunotherapy and to tailor a personalized treatment accordingly.

Moreover, the fact that bacterial peptides on tumor cells are visible to the immune system can be exploited for enhancing immunotherapy. "Many of these peptides were shared by different metastases from the same patient or by tumors from different patients, which suggests that they have a therapeutic potential and a potent ability to produce immune activation," Nagler says.

In a series of continuing experiments, Samuels and colleagues incubated T cells from melanoma patients in a laboratory dish together with bacterial peptides derived from tumor cells of the same patient. The result: T cells were activated specifically toward the bacterial peptides.

Read more at Science Daily

Childhood diet has lifelong impact

 Eating too much fat and sugar as a child can alter your microbiome for life, even if you later learn to eat healthier, a new study in mice suggests.

The study by UC Riverside researchers is one of the first to show a significant decrease in the total number and diversity of gut bacteria in mature mice fed an unhealthy diet as juveniles.

"We studied mice, but the effect we observed is equivalent to kids having a Western diet, high in fat and sugar and their gut microbiome still being affected up to six years after puberty," explained UCR evolutionary physiologist Theodore Garland.

A paper describing the study has recently been published in the Journal of Experimental Biology.

The microbiome refers to all the bacteria as well as fungi, parasites, and viruses that live on and inside a human or animal. Most of these microorganisms are found in the intestines, and most of them are helpful, stimulating the immune system, breaking down food and helping synthesize key vitamins.

In a healthy body, there is a balance of pathogenic and beneficial organisms. However, if the balance is disturbed, either through the use of antibiotics, illness, or unhealthy diet, the body could become susceptible to disease.

In this study, Garland's team looked for impacts on the microbiome after dividing their mice into four groups: half fed the standard, 'healthy' diet, half fed the less healthy 'Western' diet, half with access to a running wheel for exercise, and half without.

After three weeks spent on these diets, all mice were returned to a standard diet and no exercise, which is normally how mice are kept in a laboratory. At the 14-week mark, the team examined the diversity and abundance of bacteria in the animals.

They found that the quantity of bacteria such as Muribaculum intestinale was significantly reduced in the Western diet group. This type of bacteria is involved in carbohydrate metabolism.

Analysis also showed that the gut bacteria are sensitive to the amount of exercise the mice got. Muribaculum bacteria increased in mice fed a standard diet who had access to a running wheel and decreased in mice on a high-fat diet whether they had exercise or not.

Researchers believe this species of bacteria, and the family of bacteria that it belongs to, might influence the amount of energy available to its host. Research continues into other functions that this type of bacteria may have.

One other effect of note was the increase in a highly similar bacteria species that were enriched after five weeks of treadmill training in a study by other researchers, suggesting that exercise alone may increase its presence.

Overall, the UCR researchers found that early-life Western diet had more long-lasting effects on the microbiome than did early-life exercise.

Garland's team would like to repeat this experiment and take samples at additional points in time, to better understand when the changes in mouse microbiomes first appear, and whether they extend into even later phases of life.

Regardless of when the effects first appear, however, the researchers say it's significant that they were observed so long after changing the diet, and then changing it back.

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Follow your gut: How farms protect from childhood asthma

 We are born into an environment full of small organisms called microbiota. Within the first minutes and hours of our lives, they start challenging but also educating our immune system. The largest immune organ is our gut, where maturation of the immune system and maturation of the colonizing bacteria, the gut microbiome, go hand in hand. After profound perturbations in the first year of life, the maturation process, the composition of the gut microbiome gradually stabilizes and accompanies us for our lives. Previous research of the Munich scientists showed an asthma-protective effect by a diverse environmental microbiome, which was particularly pronounced in farm children. The question now was whether this effect could be attributed to the maturation process of the early gut microbiome.

Farm life boosts gut microbiome maturation in children The researchers analyzed fecal samples from more than 700 infants partly growing up on traditional farms between the age of 2 and 12 months who took part in PASTURE -- a European birth cohort, which runs for almost 20 years now with funding from the European Commission.

"We found that a comparatively large part of the protective farm effect on childhood asthma was mediated by the maturation of the gut microbiome in the first year of life" states Dr. Martin Depner, biostatistician at Helmholtz Zentrum München, and further concludes: "This suggests that farm children are in contact with environmental factors possibly environmental microbiota that interact with the gut microbiome and lead to this protective effect."

The researchers anticipated effects of nutrition on the gut microbiome maturation but were surprised to find strong effects of farm-related exposures such as stays in animal sheds. This emphasizes the importance of the environment for the protective effect. In addition, vaginal delivery and breastfeeding fostered a protective microbiome in the first two months of life.

Furthermore, the researchers discovered an inverse association of asthma with measured level of fecal butyrate. Butyrate is a short chain fatty acid which is known to have an asthma protective effect in mice. The researchers concluded that gut bacteria such as Roseburia and Coprococcus with the potential of producing short chain fatty acids may contribute to asthma protection in humans as well. Children with a matured gut microbiome showed a higher amount of these bacteria (Roseburia and Coprococcus) compared to other children.

"Our study provides further evidence that the gut may have an influence on the health of the lung. A mature gut microbiome with a high level of short chain fatty acids had a protective effect on the respiratory health of the children in this study. This suggests the idea of a relevant gut-lung axis in humans," says Dr. Markus Ege, professor for clinical-respiratory epidemiology at the Dr. von Hauner Children's Hospital. "This also means, however, that an immature gut microbiome may contribute to the development of diseases. This emphasizes the need for prevention strategies in the first year of life, when the gut microbiome is highly plastic and amenable to modification."

Probiotic prevention strategies The researchers demonstrated that the asthma protective effect is not dependent on one single bacteria only, but on the maturation of the entire gut microbiome. This finding questions the approach of using single bacteria as probiotics for the prevention of asthma. Probiotics should rather be tested with respect to their sustained effect on the compositional structure of the gut microbiome and its maturation early in life.

Further studies on cow milk Nutritional aspects analyzed in this study may serve as prevention strategies such as consumption of cow's milk. Unprocessed raw milk, however, cannot be recommended because of the risk of life-threatening infections such as EHEC. Scientists at the Dr. von Hauner Children's Hospital are currently running a clinical trial on the effects of minimally processed but microbiologically safe milk for the prevention of asthma and allergies (MARTHA trial).

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Researchers unlock potential to use CRISPR to alter the microbiome

Researchers at Western University have developed a new way to deliver the DNA-editing tool CRISPR-Cas9 into microorganisms in the lab, providing a way to efficiently launch a targeted attack on specific bacteria.

Published today in Nature Communications, this study opens up the possibility of using CRISPR to alter the makeup of the human microbiome in a way that could be personalized and specific from person to person. It also presents a potential alternative to traditional antibiotics to kill bacteria like Staphyloccous aureus (Staph A) or Escherichia coli (E. coli).

"One of the major reasons that I am excited about this work is that it has a wide range of possible real-world applications," said Bogumil Karas, PhD, Assistant Professor at Western's Schulich School of Medicine & Dentistry. "It has the potential for development of next generation antimicrobial agents that would be effective even for bacteria that are resistant to all known antibiotics. This technology could also be used to help 'good' bacteria produce compounds to treat diseases caused by protein deficiencies."

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats and can be programmed to target specific stretches of genetic code and to edit DNA at precise locations. Researchers use CRISPR to permanently modify genes in living cells and organisms.

In this way, CRISPR can be programmed to kill bacteria, but until now there wasn't a way to efficiently and specifically target certain bacterial strains.

"Using CRISPR to kill things isn't a new idea because that's what CRISPR does naturally," said David Edgell, PhD, Professor at Schulich Medicine & Dentistry. "The problem has always been how you get CRISPR to where you want it to go. Other delivery systems could only go to a few spots, where ours can go anywhere."

The delivery system developed at Western uses bacteria's natural ability to replicate -- called bacterial conjugation -- to deliver CRISPR to specific bacteria, in order to alter its DNA and kill it.

"Specific delivery of any therapeutic agent, including CRISPR, is usually one of the biggest bottlenecks in development of new treatments. By developing this new delivery system, we created new tools that could help us in the development of more effective therapies in the near future," said Karas.

The team says their delivery system is not only broadly applicable, but it is also more efficient than previous systems.

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New tool can pinpoint origins of the gut's bacteria

A UCLA-led research team has developed a faster and more accurate way to determine where the many bacteria that live in, and on, humans come from. Broadly, the tool can deduce the origins of any microbiome, a localized and diverse community of microscopic organisms.

The new computational tool, called "FEAST," can analyze large amounts of genetic information in just a few hours, compared to tools that take days or weeks. The software program could be used in health care, public health, environmental studies and agriculture. The study was published online in Nature Methods.

A microbiome typically contains hundreds to thousands of microbial species. Microbiomes are found everywhere, from the digestive tracts of humans, to lakes and rivers that feed water supplies. The microorganisms that make up these communities can originate from their surrounding environment, including food.

Knowing where these organisms come from and how these communities form can give scientists a more detailed picture of the unseen ecological processes that affect human health. The researchers developed the program to give doctors and scientists a more effective tool to investigate these phenomena.

The source-tracking program gives the percentage of the microbiome that came from somewhere else. It's similar in concept to a census that reveals the countries that its immigrant population came from, and what percentage each group is of the total population.

For example, using the source-tracking tool on a kitchen counter sample can indicate how much of that sample came from humans, how much came from food, and specifically which types of food.

Armed with this information, doctors will be able to distinguish a healthy person from one who has a particular disease by simply analyzing their microbiome. Scientists could use the tool to detect contamination in water resources or in food supply chains.

"The microbiome has been linked to many aspects of human physiology and health, yet we are just in the early stages of understanding the clinical implications of this dynamic web of many species and how they interact with each other," said Eran Halperin, the study's principal investigator who holds UCLA faculty appointments in the Samueli School of Engineering and in the David Geffen School of Medicine.

"There has been an unprecedented expansion of microbiome data, which has rapidly increased our knowledge of the diverse functions and distributions of microbial life," Halperin added. "Nonetheless, such big and complex datasets pose statistical and computational challenges."

Compared to other source-tracking tools, FEAST is up to 300 times faster, and is significantly more accurate, the researchers say.

Also, current tools can only analyze smaller datasets, or only target specific microorganisms that are deemed to be harmful contaminants. The new tool can process much larger datasets and offer a more complete picture of the microorganisms that are present and where they came from, the researchers say.

The researchers confirmed FEAST's viability by comparing it against analyses of previously published datasets.

For example, they used the tool to determine the types of microorganisms on a kitchen counter and it provided much more detail than previous tools that analyzed the same dataset.

They also used the tool to compare the gut microbiomes of infants delivered by cesarean section to the microbiomes of babies who were delivered vaginally.

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Immigration to the United States changes a person's microbiome

This graphical abstract shows that migration from a non-western nation to the United States is associated with a loss in gut microbiome diversity and function in a manner that may predispose individuals to metabolic disease.

Researchers at the University of Minnesota and the Somali, Latino, and Hmong Partnership for Health and Wellness have new evidence that the gut microbiota of immigrants and refugees rapidly Westernize after a person's arrival in the United States. The study of communities migrating from Southeast Asia to the U.S., published November 1 in the journal Cell, could provide insight into some of the metabolic health issues, including obesity and diabetes, affecting immigrants to the country.

"We found that immigrants begin losing their native microbes almost immediately after arriving in the U.S. and then acquire alien microbes that are more common in European-American people," says senior author Dan Knights, a computer scientist and quantitative biologist at the University of Minnesota. "But the new microbes aren't enough to compensate for the loss of the native microbes, so we see a big overall loss of diversity."

It has been shown before that people in developing nations have a much greater diversity of bacteria in their gut microbiome, the population of beneficial microbes living in humans' intestines, than people living in the U.S. "But it was striking to see this loss of diversity actually happening in people who were changing countries or migrating from a developing nation to the U.S.," he says.

The research was conducted with assistance from -- and inspired by -- Minnesota's large community of refugees and immigrants from Southeast Asia, particularly the Hmong and Karen peoples, ethnic minorities that originally were from China and Burma and that today have communities in Thailand. The study used a community-based participatory research approach: members of the Hmong and Karen communities in both Minnesota and Thailand were involved in designing the study, recruiting participants, and educating their communities about the findings.

"Obesity was a concern that was coming up a lot for the Hmong and Karen communities here. In other studies, the microbiome had been related to obesity, so we wanted to know if there was potentially a relationship in immigrants and make any findings relevant and available to the communities. These are vulnerable populations, so we definitely try to make all of our methods as sensitive to that as possible and make sure that they have a stake in the research," says first author Pajau Vangay.

Knights, Vangay, and their team compared the gut microbiota of Hmong and Karen people still living in Thailand; Hmong and Karen people who had immigrated to the U.S.; the children of those immigrants; and Caucasian American controls. They also were able to follow a group of 19 Karen refugees as they relocated from Thailand to the U.S., which meant they could track how the refugees' gut microbiomes changed longitudinally in their first six to nine months in the U.S.

And the researchers did find that significant changes happened that fast: in those first six to nine months, the Western strain Bacteroides began to displace the non-Western bacteria strain Prevotella. But this Westernization also continued to happen over the course of the first decade in the U.S., and overall microbiome diversity decreased the longer the immigrants had been in the U.S. The participants' food logs suggested that eating a more Western diet played a role in perturbing the microbiome but couldn't explain all the changes.

The changes were even more pronounced in their children. "We don't know for sure why this is happening. It could be that this has to do with actually being born in the USA or growing up in the context of a more typical US diet. But it was clear that the loss of diversity was compounded across generations. And that's something that has been seen in animal models before, but not in humans," says Knights.

Although the research didn't establish a cause-and-effect relationship between the microbiome changes in immigrants and the immigrant obesity epidemic, it did show a correlation: greater westernization of the microbiome was associated with greater obesity.

Knights believes that this research has a lot to tell us about our health. "When you move to a new country, you pick up a new microbiome. And that's changing not just what species of microbes you have, but also what enzymes they carry, which may affect what kinds of food you can digest and how your diet interacts with your health," he says. "This might not always be a bad thing, but we do see that Westernization of the microbiome is associated with obesity in immigrants, so this could an interesting avenue for future research into treatment of obesity, both in immigrants and potentially in the broader population."

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Cancer hijacks the microbiome to glut itself on glucose

Cancer needs energy to drive its out-of-control growth. It gets energy in the form of glucose, in fact consuming so much glucose that one method for imaging cancer simply looks for areas of extreme glucose consumption -- where there is consumption, there is cancer. But how does cancer get this glucose? A University of Colorado Cancer Center study published today in the journal Cancer Cell shows that leukemia undercuts the ability of normal cells to consume glucose, thus leaving more glucose available to feed its own growth.

"Leukemia cells create a diabetic-like condition that reduces glucose going to normal cells, and as a consequence, there is more glucose available for the leukemia cells. Literally, they are stealing glucose from normal cells to drive growth of the tumor," says Craig Jordan, PhD, investigator at University of Colorado Cancer Center, division chief of the Division of Hematology and the Nancy Carroll Allen Professor of Hematology at the University of Colorado School of Medicine.

Like diabetes, cancer's strategies depend on insulin. Healthy cells need insulin to use glucose. In diabetes, either the pancreas under-produces insulin or tissues cannot not respond to insulin and so cells are left starved for energy while glucose builds up in the blood. The current study shows that leukemia goes about creating similar conditions of glucose buildup in two ways.

First, tumor cells trick fat cells into over-producing a protein called IGFBP1. This protein makes healthy cells less sensitive to insulin, meaning that when IGFBP1 is high, it takes more insulin to use glucose than it does when IGFBP1 is low. Unless the supply of insulin goes up, high IGFBP1 means that the glucose consumption of healthy cells goes down. (This protein may also be a link in the chain connecting cancer and obesity: The more fat cells, the more IGFBP1, and the more glucose is available to the cancer.)

Of course, cancer has a second strategy that ensures insulin production does not go up to meet the need created by increased IGFBP1. In fact, cancers turn insulin production down. In large part, they do this in the gut.

"In the course of doing this systemic analysis, we realized that some of the factors that help regulate glucose are made by the gut or bacteria in the gut. We looked there and found that the composition of the microbiome in leukemic animals was different than in control mice," Jordan says.

One major difference in the guts of leukemic mice was the lack of a specific kind of bacteria known as bacteroids. These bacteroids produce short-chain fatty acids that in turn feed the health of cells lining your gut. Without bacteroids, gut health suffers. And the current study shows that without bacteroids, gut health suffers in ways that specifically aid cancer.

One way is the loss of hormones called incretins. When blood glucose gets high, for example after you eat, your gut releases incretins, which tamp down blood glucose, reducing it back into the normal range. Working through the gut, leukemia inactivates these incretins, allowing blood glucose to remain higher than it should. Leukemia also nixes the activity of serotonin. Serotonin is well-known as a "feel good" chemical that helps to regulate mood and is found in many antidepressants. But serotonin is also essential for the manufacture of insulin in the pancreas, and by attacking serotonin, leukemia reduces insulin production (and thus, down the line, glucose use).

The result of less insulin secretion and less insulin sensitivity is that cancer undercuts healthy cells' use of insulin from both sides: Healthy cells need more insulin, just as there is less insulin available. Less insulin use by healthy cells leaves more glucose for the cancer.

"It's a classic parasite trick: Take advantage of something the host does and subvert it for your own purposes," Jordan says.

Interestingly, just as a parasite might eat a host's food leading to malnourishment, cancer's energy theft may play a role in the fatigue and weight loss common in cancer patients.

"The fairly prevalent observation is that cancer patients have a condition called cachexia, basically wasting away -- you lose weight. If cancers are inducing systemic changes that result in depletion of normal energy stores, this could be part of that story," Jordan says.

However, Jordan and colleagues including first author Haobin Ye, PhD, not only showed how leukemia dysregulates healthy cells' glucose consumption, but also showed how to "re-regulate" this consumption.

"When we administered agents to recalibrate the glucose system, we found that we could restore glucose regulation and slow the growth of leukemia cells," Ye says.

These "agents" were surprisingly low-tech. One was serotonin. Another was tributyrin, a fatty acid found in butter and other foods. Serotonin supplementation replaced the serotonin nixed by leukemia and tributyrin helped to replace the short-chain fatty acids that were absent due to loss of bacteroids.

The group calls the combination Ser-Tri therapy. And they show that it is more than a theory. Ser-Tri therapy led to the recovery of insulin levels and reduction of IGFPB1. And leukemic mice treated with Ser-Tri therapy lived longer than those without. Twenty-two days after leukemia was introduced in mice, all of the untreated mice had died, while more than half of the mice treated with Ser-Tri were still alive.

The continuing line of work shows that cancer may depend on the ability to out-compete healthy cells for limited energy. Healthy tissues have strategies to regulate insulin, glucose and other factors controlling energy consumption; cancer cells have strategies to subvert this regulation with the goal of making more energy available for their own use.

"We now have evidence that what we observed in our mouse models is also true for leukemia patients." Ye says.

Understanding these mechanisms that cancer uses to unbalance the body's system of energy in their favor is helping doctors and researchers learn to thumb the scale in favor of healthy cells.

Read more at Science Daily

Gut bacteria's shocking secret: They produce electricity

Listeria bacteria transport electrons through their cell wall into the environment as tiny currents, assisted by ubiquitous flavin molecules (yellow dots).

While bacteria that produce electricity have been found in exotic environments like mines and the bottoms of lakes, scientists have missed a source closer to home: the human gut.

University of California, Berkeley, scientists discovered that a common diarrhea-causing bacterium, Listeria monocytogenes, produces electricity using an entirely different technique from known electrogenic bacteria, and that hundreds of other bacterial species use this same process.

Many of these sparking bacteria are part of the human gut microbiome, and many, like the bug that causes the food-borne illness listeriosis, which can also cause miscarriages, are pathogenic. The bacteria that cause gangrene (Clostridium perfringens) and hospital-acquired infections (Enterococcus faecalis) and some disease-causing streptococcus bacteria also produce electricity. Other electrogenic bacteria, like Lactobacilli, are important in fermenting yogurt, and many are probiotics.

"The fact that so many bugs that interact with humans, either as pathogens or in probiotics or in our microbiota or involved in fermentation of human products, are electrogenic -- that had been missed before," said Dan Portnoy, a UC Berkeley professor of molecular and cell biology and of plant and microbial biology. "It could tell us a lot about how these bacteria infect us or help us have a healthy gut."

The discovery will be good news for those currently trying to create living batteries from microbes. Such "green" bioenergetic technologies could, for example, generate electricity from bacteria in waste treatment plants.

The research will be posted online Sept. 12 in advance of Oct. 4 print publication in the journal Nature.

Breathing metal

Bacteria generate electricity for the same reason we breathe oxygen: to remove electrons produced during metabolism and support energy production. Whereas animals and plants transfer their electrons to oxygen inside the mitochondria of every cell, bacteria in environments with no oxygen -- including our gut, but also alcohol and cheese fermentation vats and acidic mines -- have to find another electron acceptor. In geologic environments, that has often been a mineral -- iron or manganese, for example -- outside the cell. In some sense, these bacteria "breathe" iron or manganese.

Transferring electrons out of the cell to a mineral requires a cascade of special chemical reactions, the so-called extracellular electron transfer chain, which carries the electrons as a tiny electrical current. Some scientists have tapped that chain to make a battery: stick an electrode in a flask of these bacteria and you can generate electricity.

The newly discovered extracellular electron transfer system is actually simpler than the already known transfer chain, and seems to be used by bacteria only when necessary, perhaps when oxygen levels are low. So far, this simpler electron transfer chain has been found in bacteria with a single cell wall -- microbes classified as gram-positive bacteria -- that live in an environment with lots of flavin, which are derivatives of vitamin B2.

"It seems that the cell structure of these bacteria and the vitamin-rich ecological niche that they occupy makes it significantly easier and more cost effective to transfer electrons out of the cell," said first author Sam Light, a postdoctoral fellow. "Thus, we think that the conventionally studied mineral-respiring bacteria are using extracellular electron transfer because it is crucial for survival, whereas these newly identified bacteria are using it because it is 'easy.'"

To see how robust this system is, Light teamed up with Caroline Ajo-Franklin from Lawrence Berkeley National Laboratory, who explores the interactions between living microbes and inorganic materials for possible applications in carbon capture and sequestration and bio-solar energy generation.

She used an electrode to measure the electric current that streams from the bacteria -- up to 500 microamps -- confirming that it is indeed electrogenic. In fact, they make about as much electricity -- some 100,000 electrons per second per cell -- as known electrogenic bacteria.

Light is particularly intrigued by the presence of this system in Lactobacillus, bacteria crucial to the production of cheese, yogurt and sauerkraut. Perhaps, he suggests, electron transport plays a role in the taste of cheese and sauerkraut.

"This is a whole big part of the physiology of bacteria that people didn't realize existed, and that could be potentially manipulated," he said.

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Microbiome differences between urban and rural populations start soon after birth

This graphical abstract illustrates factors that affect the fecal microbiome and metabolome of rural Bassa and urban individuals from Nigeria, including infants. The findings stress the loss of ancient signatures along with urbanization and support distinct trajectories of development of the intestinal ecosystem in early life, depending on human subsistence.

An analysis comparing the intestinal microbiomes of both infants and adults living in rural and urban areas of Nigeria has revealed that not only are there many differences in adults living in subsistence environments versus urban ones but also that these variations begin at a very young age. The study appears June 5 in the journal Cell Reports.

"We've always assumed that the microbiomes of infants were the same everywhere, and that differences came later in life," says senior author Silvia Turroni of the Department of Pharmacy and Biotechnology at the University of Bologna in Italy. "We were surprised to find that the microbiomes of infants living in rural areas were missing components that we have long believed were standard to all infant populations -- especially that they were essentially devoid of Bifidobacterium." Bifidobacterium dominates the microbiomes of Western infants and has been considered a key element to healthy growth and development.

Previous studies that have analyzed the microbiomes of rural, hunter-gatherer societies have generally compared them to distant urban populations in Europe or the United States. This study was unique in that it looked at rural and urban African people in the same geographic area. Urban populations in the study were drawn from four state capital cities in Nigeria and the national capital, Abuja.

"This research was specifically designed to fill in gaps of knowledge about the variation of the human gut microbiome, as well as the metabolome, in relation to subsistence patterns in geographically close populations," says first author Funmilola Ayeni of the Department of Pharmaceutical Microbiology at the University of Ibadan in Nigeria.

This study was also unique because it looked at both infant and adult microbiomes. For the purposes of this study, infants were defined as children up to age three. Unexpectedly, the investigators found that infants living in rural areas had microbiome profiles that were overall more diverse and more like those of adults.

The rural people included in the study, an agricultural society called the Bassa, consume a diet consisting of tubers, grains, and leafy soups, as well as untreated water. The urban diet contained processed foods and treated water but had more elements of a traditional Nigerian diet than what is seen in Western countries. Rural infants were given foods other than breast milk at a younger age than urban infants were.

Although it is only one factor, diet is an important component affecting the makeup of the intestinal microbiota. The researchers found that the rural population had a higher level of certain bacterial species that are important for digesting fiber. In addition, when metabolites in the samples were analyzed, rural populations had lower levels of amino acids and biogenic amines, suggesting a lower consumption of protein.

There were some drawbacks to the study. For one, the Bassa people usually don't know their exact ages. Also, data about gender were not collected for the Bassa who participated, so the researchers were not able to look at whether there were differences between the sexes.

Still, the findings were notable. "Studies like these have profound evolutionary relevance because they recall ways of life that have characterized human history, from the hunting and gathering of our Paleolithic ancestors to small-scale agriculture, to the postindustrial Western lifestyle," Turroni says.

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What the gorilla microbiome tells us about evolution and human health

A study of the microbiomes of wild gorillas and chimpanzees offers insights into the evolution of the human microbiome and might even have implications for human health. The research project was led by scientists at the Center for Infection and Immunity (CII) at Columbia University's Mailman School of Public Health. Findings appear in the journal Nature Communications.

The researchers used genetic sequencing to analyze fecal samples collected by the Wildlife Conservation Society (WCS) from wild African great apes living the Sangha region of the Republic of Congo over the course of three years. Their goal was to understand the mix of gut microbes living in gorillas and chimpanzees and compare them to those already documented in other non-human primates and human populations. They found that gorilla and chimpanzee microbiomes fluctuate with seasonal rainfall patterns and diet, switching markedly during the summer dry period when succulent fruits abound in their environment and make up a larger proportion of their diet, as opposed to their usual, more fiber-rich diet of leaves and bark.

These seasonal shifts in the microbiomes of gorillas and chimpanzees are similar to seasonal microbiome changes observed in the human Hadza hunter-gatherers from Tanzania, who also rely heavily on the seasonal availability of foods in their environment. Seasonal shifts in the microbiomes of human industrialized cultures, such as the United States, are likely less prevalent owing to reduced reliance on seasonally available foods and globalization of the food supply, as evident in any grocery store.

"While our human genomes share a great deal of similarity with those of our closest living relatives, our second genome (the microbiome) has some important distinctions, including reduced diversity and the absence of bacteria and archaea that appear to be important for fiber fermentation," says first author Allison L. Hicks, MS, a researcher at CII. "Understanding how these lost microbes influence health and disease will be an important area for future studies."

"We observed dramatic changes in the gorilla and chimpanzee microbiomes depending on seasons and what they are eating," says senior author Brent L. Williams, PhD, assistant professor of Epidemiology at CII. "Bacteria that help gorillas break down fibrous plants are replaced once a year by another group of bacteria that feed on the mucous layer in their gut during the months they are eating fruits.

"The fact that our microbiomes are so different from our nearest living evolutionary relatives says something about how much we've changed our diets, consuming more protein and animal fat at the expense of fiber," says Williams. "Many humans may be living in a constant state of fiber deficiency. Such a state may be promoting the growth of bacteria that degrade our protective mucous layer, which may have implications for intestinal inflammation, even colon cancer."

All great apes are endangered or critically endangered. Down to fewer than 500,000, their numbers have been reduced through deforestation-which destroys their habitat-and through hunting, including for meat. Even infectious disease is a major factor-as many as one-quarter of the world's gorilla population has died because of Ebola.

"We are losing biodiversity on a global scale," cautions co-author Sarah Olson, PhD, associate director of wildlife health at WCS. "In fact, our own human microbiome is not immune to this phenomenon. There is an ever growing need for conservation efforts to preserve environments that are vital to the health of animal populations."

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