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Category: human microbiome

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Something new and complex to think about. We humans  have genes (about 20, 000), and then the microbes (bacteria, viruses, fungi) within us have genes (between 2 million and 20 million) . And now it looks like some of their genes have slipped into our genes (horizontal gene transfer). An example: the genes that determine blood types (A, B, O) . Whew....Another totally new thing to think about in our evolutionary history. From Time:

You may be your germs: Microbe genes slipped into human DNA, study says

Evolutionary diagrams usually connect humans and monkeys with common primate ancestors, but now, scientists say there's a missing link that deserves a spot on that family tree -- our bacteria, fungi, and viruses. Though most of our genes come from primate ancestors, many of them slipped into our DNA from microbes living in our bodies, says British researcher Alastair Crisp. It's called horizontal gene transfer. Scientists have known of examples of this for a long time: Bacteria slip genes to each other, and it helps them evolve. 

Some researchers have disputed that microbes have swapped genes with the cells of complex animals, such as humans. But a new study at the University of Cambridge indicates it has probably happened a lot. Humans may have as many as hundreds of so-called foreign genes they picked up from microbes.

"Surprisingly, far from being a rare occurrence, it appears that (horizontal gene transfer) has contributed to the evolution of many, perhaps all, animals and that the process is ongoing, meaning that we may need to re-evaluate how we think about evolution," Crisp said.

That may not surprise microbiologists.We humans and other complex animals are full of microbes, gajillions of them. People have so many that microbe cells living in our bodies outnumber our own vastly. A body has about 10 trillion human cells, says microbiologist Rob Knight. The microbe cells living inside of us number around 100 trillion. That's a ratio of 10 to one. The biggest collection is in our gut.

They're mostly helpful, and we we'd have a hard time living without them. Their genetic material dwarfs ours. The human genome adds up to 20,000 genes. The collective genomes of the many varieties of microbes in our bodies adds up to between 2 million and 20 million, Knight says.

In recent decades, scientists laid down genomes -- a detailed description of gene sequences -- for all kinds of species, including humans. The Cambridge researchers compared the genomes of various species of fruit flies, worms and primates, including humans.

They calculated similarities and differences between the genes across those species to look for ones that stuck out as not being part of a smooth evolutionary lineage, but instead probably popped in at some point. They found 128 formerly unidentified "foreign" genes in humans and confirmed 17 that had previously been reported. Most of them play a role in digestion. But the scientists also found that the gene that determines blood types -- A, B and O -- is "foreign." Some "foreign" genes that transferred in from microbes help our bodies' immune systems defend against microbial infections like bacteria and fungi.

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Are there differences between male and female gut microbiomes? (NOTE: gut microbiome is the community of microbes living in the gut.) I always thought YES, based on that there seem to be so many biological differences between males and females. But according to this blog entry from uBiome (a microbiome sequencing service which has analyzed thousands of gut microbiomes - the microbes living in the gut ) there aren't. They only looked at gut microbiomes (by analyzing fecal samples), and not at other body sites in this comparison. Other past studies have found  that other body sites have bacteria differences. Even the comments after the post were interesting. From the uBiome Blog:

A Surprising Comparison of Male vs. Female Microbiomes

I must admit, I was curious. So I went over to the desk of our brilliant Lead Data Scientist, Dr. Siavosh Rezvan-Behbahani, to find out. Could you look at all of uBiome’s gut samples, I asked, and see what the difference in microbiome composition is between men and women? And the corollary, is it possible to predict from microbiomial data whether the person giving the sample was male or female? With human DNA, of course you can determine gender based on the chromosome signature XX vs. XY. But does the microbiome have a gender signature too?

Siavosh dove in. He spent many hours analyzing, plotting numbers, running different machine learning classifier algorithms. He looked at healthy male and female samples in part of our dataset, all the way down to genus level. And here’s what he found, which blew my mind.

It turns out that in our dataset, there is no statistically significant difference between male microbiomes and female microbiomes. And, given a random sample, we would not be able to determine if it came from a man or a woman.

This result is fascinating to me, because it suggests that maybe men and women aren’t that different in some ways. We all have two eyes, and belly buttons, and similar proportions of bacteria swimming around inside our intestines.

(Of course there’s the standard disclaimer that this is just what we observe in our gut dataset, and may not be representative of the entire human population. It’s also possible that there is a difference but it’s much more subtle than we expect. In any case, this result is encouraging me to think up other questions to ask!)

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This interesting study raises the possibility that eating certain foods or probiotics  (beneficial bacteria) may prevent diabetes. Note that Akkermansia is a bacteria with one species Akkermansia muciniphila . In Wikipedia:"Researchers have discovered that Akkermansia muciniphila may be able to be used to combat obesity and type 2 diabetes...The bacterium is naturally present in the human digestive tract at 3-5%, but has been seen to fall with obesity." Regarding Prevotella, in Wikipedia: "Studies also indicate that long-term diet is strongly associated with the gut microbiome composition—those who eat plenty of protein and animal fats typical of Western diet have predominantly Bacteroides bacteria, while for those who consume more carbohydrates, especially fiber, the Prevotella species dominate." From Science Daily:

Gut bacteria may contribute to diabetes in black males

African American men at elevated risk for developing type 2 diabetes may have fewer beneficial and more harmful intestinal bacteria, according to new research.

"The 'signature' of the gut microbiota -- the relative abundance of various bacteria and other microbes in the digestive system -- could be another useful tool in assessing a person's risk for developing diabetes," said Ciubotaru. Ciubotaru and her colleagues, including principal investigator Dr. Elena Barengolts,... found that a specific microbiota is associated with stable, normal blood glucose levels, while a different profile is associated with glucose levels that indicate pre-diabetes.

"The study provides additional reasons for physicians to recommend foods, such as prebiotics, which improve the growth and activity of helpful gut bacteria," said Barengolts. The gut microbiota helps digest food; fights infections; and plays an important role in keeping the immune system healthy. It is greatly influenced by genetics, diet and other environmental factors. Previous research has implicated an unhealthy or unbalanced microbiota as a contributing factor to metabolic disorders, including obesity and diabetes. The species that make up an individual's gut microbiota, as well as their abundance, can be identified by stool sample analysis.

The researchers determined the gut microbiotas of 116 African-American male veterans, age 45 to 75, participating in the D Vitamin Intervention in VA, or DIVA study. The aim of the DIVA study, which has 173 total participants and is funded by the Department of Veterans Affairs, is to determine if vitamin D supplementation can prevent diabetes in men with risk factors for developing the disease.

Participants were divided into four groups based on changes in their blood sugar levels as determined at the start and end of the one-year study. The groups included men whose glucose levels remained normal (non-pre-diabetic); those with stable levels indicative of pre-diabetes; those whose levels indicated a worsening of glucose control; and those whose levels improved. All the men provided stool samples for analysis of their gut microbiota.

Men whose blood sugar levels stayed normal over the year had more gut bacteria that are considered beneficial for metabolic health, whereas those who stayed pre-diabetic had fewer beneficial bacteria and more harmful bacteria. In addition, the group whose levels improved had more abundant Akkermansia--healthy bacteria--than the group that maintained normal blood sugar control throughout the year.

The study suggests that differences in the gut microbiota already exist in pre-diabetes, Barengolts said. Although the study found connections between composition of the gut microbiota and blood sugar control, Barengolts said further research is needed to confirm these findings and evaluate whether certain intestinal bacteria cause type 2 diabetes. However, based on other research her group has conducted and studies in animals, she speculated that the foods we eat affect our diabetes risk through our gut microbiota. If the mix of organisms in the intestinal tract is indeed responsible for the development of type 2 diabetes, she said, it may be possible to lower one's risk by changing the gut bacteria.

More details about that same study. From Medpage Today:

Prediabetes Patients Have Fewer Gut Bugs

They were put into one of four groups: those with a stable glucose tolerance, those with stable impaired fasting glucose or stable impaired glucose tolerance, those with worsened glucose tolerance, and those with improved glucose tolerance. There were significant differences in bacterial composition between the first and second groups (P=0.03) at the phylum level. Bacteroidetes was higher and Firmicutes was lower with worse glycemic control in the second group. 

Proteobacteria decreased over the period in groups 2 and 4 compared with group 1 (P=0.04 for both). At the family and genus levels, in group 2 versus group 1 there was less Prevotella, and a higher Bacteroides/Prevotella ratio in the second group at 5.6 to 2.7 (P=0.05). There was also less Enterobacteriaceae (P=0.03), and more Ruminococcae (P=0.01) and Veillonellaceae (P=0.02).

"We speculate that lower abundance of Prevotella may be associated with worsening glycemia, and, conversely, higher abundance of Akkermansia might be associated with improving glycemia, thus corroborating suggestions from previous studies," the researchers said.

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Research is accumulating that the microbial exposure from a vaginal birth, breastfeeding, and pets in the first year of life are all good for a baby's developing immune system and the gut microbiome.

From Science Daily: Breastfeeding, other factors help shape immune system early in life

Researchers say that breastfeeding and other factors influence a baby's immune system development and susceptibility to allergies and asthma by what's in their gut. The striking findings from a series of studies further advance the so-called hygiene hypothesis theory that early childhood exposure to microorganisms affects the immune system's development and onset of allergies, says Christine Cole Johnson, Ph.D., MPH, chair of Henry Ford's Department of Public Health Sciences and principal research investigator.

The gut microbiome is the collection of microorganisms in the gastrointestional, or GI, tract, and the human body has billions of these microbes... The gut microbiome is known to play an important role in immune system development, and is thought to contribute to a host of diseases like obesity, autoimmune diseases, circulating disorders and pediatric allergies and infection.

"For years now, we've always thought that a sterile environment was not good for babies. Our research shows why. Exposure to these microorganisms, or bacteria, in the first few months after birth actually help stimulate the immune system," Dr. Johnson says."The immune system is designed to be exposed to bacteria on a grand scale. If you minimize those exposures, the immune system won't develop optimally."

In six separate studies, researchers sought to evaluate whether breastfeeding and maternal and birth factors had any effect on a baby's gut microbiome and allergic and asthma outcomes. Using data collected from the WHEALS birth cohort, researchers analyzed stool samples from infants taken at one month and six months after birth. They also looked at whether the gut microbiome impacted the development of regulatory T-cells, or Treg, which are known to regulate the immune system. Highlights:

• Breastfed babies at one month and six months had distinct microbiome compositions compared to non-breastfed babies. These distinct compositions may influence immune system development. • Breastfed babies at one month were at decreased risk of developing allergies to pets. • Asthmatic children who had nighttime coughing or flare-ups had a distinct microbiome composition during the first year of life. • For the first time, gut microbiome composition was shown to be associated with increasing Treg cells.

Researchers found that a baby's gut microbiome patterns vary by: • A mother's race/ethnicity. • A baby's gestational age at birth. • Prenatal and postnatal exposure to tobacco smoke. • Caesarean section versus vaginal delivery.• Presence of pets in the home.

Henry Ford's landmark 2002 study found exposure to dogs or cats in the first year of a baby's life reduced their risk for allergies.

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Gut bacteria in children varies among different Asian countries. A recent study found that microbiota of 303 subjects could be classified into two main clusters: driven by Prevotella (P-type) or by Bifidobacterium/Bacteroides (BB-type).

The majority of children in China, Japan and Taiwan harbored Bifidobacterium/Bacteroides (BB type), whereas those from Indonesia and Khon Kaen in Thailand mainly harbored Prevotella (P-type). It was interesting in that even eating different types of rice result in different gut bacteria.

From Asian Scientist: Diet, Location And Your Kid’s Gut Bacteria

An Asia-wide study of the gut microbiota of primary school children has identified differences linked to diet and geographical location.  ...continue reading "Gut Bacteria of School Children In Different Asian Countries"

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This research suggests that emulsifiers (which are added to most processed foods to aid texture and extend shelf life) can alter the gut microbiota (the community of microbes that live in our gut) in such a way as to cause intestinal inflammation. Even though the study was done on mice, it is thought it also applies to humans. From Medical Daily:

You Are What You Eat: Food Additive Emulsifier Inflames Mouse Gut And Causes Obesity

Processed foods have changed the way we eat. Food can sit longer on shelves, but what does that mean for the stomach? In a new study published in the journal Nature, researchers from Georgia State University investigated how the widely used processed food additive emulsifiers played a role in the gut.

Emulsifiers are added to most processed foods in order to extend shelf life and add texture to the foods. The research team decided to feed mice a couple of the most common emulsifiers on the market — polysorbate 80 and carboxymethylcellulose — at doses comparable to a human’s consumption of processed foods. They watched the emulsifier change the mice’s gut microbiota, which is an individual’s personal 100 trillion bacteria inside the intestinal tract. Not only did this increase their chance of developing obesity-related disorders, but also inflammatory bowel disease. It’s no coincidence both conditions have been increasing since the 1950s.

"The dramatic increase in these diseases has occurred despite consistent human genetics, suggesting a pivotal role for an environmental factor," the study’s coauthor Benoit Chassaing, a researcher from GSU’s Institute for Biomedical Sciences, said in a press release. "Food interacts intimately with the microbiota, so we considered what modern additions to the food supply might possibly make gut bacteria more pro-inflammatory."

The emulsifiers, which are groups of oil-and water-friendly molecules, help to hold food together. Mayonnaise without emulsifiers, for example, will separate from an oily top layer to a thicker white layer that rests on the bottom of the jar. Once the emulsifiers were digested by the mice, their blood-glucose levels went awry, inflamed their intestinal mucus layer, which left them with weight gain, specifically concentrated in the abdomen. The bacterial changed triggered chronic colitis from causing intestinal inflammation and metabolic syndrome, which includes obesity, hyperglycemia, and insulin resistance.

Ultimately, microbiologists say you are what you eat. If your diet is smeared with margarine, mayonnaise, creamy sauces, candy, ice cream, and most other packaged and processed baked goods, you and your gut may be at risk. "We do not disagree with the commonly held assumption that over-eating is a central cause of obesity and metabolic syndrome," the study’s coauthor Andrew T. Gewirtz, a researcher from GSU’s Institute for Biomedical Sciences, said in a press release. "Rather, our findings reinforce the concept suggested by earlier work that low-grade inflammation resulting from an altered microbiota can be an underlying cause of excess eating."

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Chronic inflammation can have a variety of negative health effects. From Time:

13 Ways Inflammation Can Affect Your Health

You can't live without inflammation, but it can also be hazardous to your health. You’ve heard of anti-inflammatory medications and anti-inflammatory diets, but do you really know what inflamation is? In short, it’s the body’s response to outside threats like stress, infection, or toxic chemicals. When the immune system senses one of these dangers, it responds by activating proteins meant to protect cells and tissues. “In a healthy situation, inflammation serves as a good friend to our body,” says Mansour Mohamadzadeh, PhD, director of the Center for Inflammation and Mucosal Immunology at the University of Florida.” “But if immune cells start to overreact, that inflammation can be totally directed against us.” This type of harmful, chronic inflammation can have a number of causes, including a virus or bacteria, an autoimmune disorder, sugary and fatty foods, or the way you handle stress. Here are a few ways it can affect your health, both short-term and long.

It fights infection.Inflammation is most visible (and most beneficial) when it’s helping to repair a wound or fight off an illness...It prepares you for battles Another type of inflammation occurs in response to emotional stress. Instead of blood cells rushing to one part of the body, however, inflammatory markers called C-reactive proteins are released into the blood stream and travel throughout the body.

It can harm your gut Many of the body’s immune cells cluster around the intestines, says Denning. Most of the time, those immune cells ignore the trillions of healthy bacteria that live in the gut. “But for some people, that tolerance seems to be broken,” says Denning, “and their immune cells begin to react to the bacteria, creating chronic inflammation.” The immune cells can attack the digestive tract itself, an autoimmune condition known as inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease. 

It can harm your joints When inflammation occurs in the joints, it’s can cause serious damage. One joint-damaging condition is rheumatoid arthritis(RA)—another example of an autoimmune disorder that appears to have a genetic component, but is also linked to smoking, a lack of vitamin D, and other risk factors.

It’s linked to heart disease Any part of your body that’s been injured or damaged can trigger inflammation, even the insides of blood vessels. The formation of fatty plaque in the arteries can trigger chronic inflammation. The fatty plaques attract white blood cells, grow larger, and can form blood clots, which can cause a heart attack.Obesity and unhealthy eating increases inflammation in the body.

It’s linked to a higher risk of cancer Chronic inflammation has been linked to cancers of the lung, esophagus, cervix, and digestive tract, among others..The inflammation may be due to obesity, a chronic infection, a chemical irritant, or chronic condition; all have been linked to a higher cancer risk....It may sabotage your sleep In a 2009 study from Case Western Reserve University, people who reported sleeping more or less than average had higher levels of inflammation-related proteins in their blood than those who said they slept about 7.6 hours a night.

It’s bad for your lungs When inflammation occurs in the lungs, it can cause fluid accumulation and narrowing of the airways, making it difficult to breathe...Smoking, exposure to air pollution or household chemicals, being overweight, and even consumption of cured meats have been linked to lung inflammation... It damages gums Inflammation can also wreak havoc on your mouth in the form of periodontitis, a chronic inflammation of the gums caused by bacteria accumulation. 

It makes weight loss more difficult Obesity is a major cause of inflammation in the body, and losing weight is one of the most effective ways to fight it. But that’s sometimes easier said than done, because elevated levels of inflammation-related proteins can also make weight loss more difficult than it should be.... Inflammation can also increase insulin resistance (which raises your risk for diabetes) and has been linked with future weight gain.

It damages bones Inflammation throughout the body can interfere with bone growth and even promote increased bone loss, according to a 2009 review study published in the Journal of Endocrinology.  It affects your skin The effects of inflammation aren’t just internal: They can also be reflected on your skin. Psoriasis, for example, is an inflammatory condition that occurs when the immune system causes skin cells to grow too quickly. .... It’s linked with depression 

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Nice summary of cancer prevention advice. What it boils down to is that there is no magic bullet for cancer prevention (maybe the closest thing is to NOT smoke), but it's a lot of little things adding up (your lifestyle) that lowers the risk of cancer. From The Washington Post:

Looking for that fruit or vegetable that might prevent cancer?

Blueberries. Green tea. Tomatoes. And, oh, that cruciferous cauliflower. All make the lists of super foods that might help prevent cancer. Then there are the foods such as smoked meat and fried foods that supposedly might cause cancer. Such information is standard fare for TV doctors and Web sites, but most of us don’t know how to judge such claims. What sounds authoritative may not be. Only about half of the recommendations on two internationally syndicated TV medical talk shows were supported by scientific evidence, according to a recent study in the journal BMJ.

Of course, the blueberries we eat today are good for us. But nutrition’s role in cancer prevention is much more complex than a single dietary component: Evidence has mounted, for example, that lifestyle — diet, weight control and exercise — is vital in helping reduce risk. For now, experts endorse general dietary advice that is healthful for a variety of chronic diseases and conditions, rather than reductionist thinking that focuses on single foods or nutrients.

When you hear that a certain food helps prevent cancer, ask: Which cancer? “Cancer is multiple diseases,” said Marian Neuhouser, a nutritional epidemiologist at the Fred Hutchinson Cancer Research Center in Seattle. Whereas cardiovascular disease might be broken down into several types, including myocardial infarction, stroke and peripheral vascular disease, she said, “for cancer, it’s really over 100 different diseases.” “Cancer is a very complex, very challenging disease to study whether you’re looking at it on the cell level or the clinical level or the epidemiologic and preventive level,” Willett said.

Researchers caution about overreacting to a single study. New findings come out every week, but “we never take any one study to be the answer to anything,” said Nancy Potischman, a nutritional epidemiologist at the National Cancer Institute. Only if the same results come up in multiple studies across multiple populations, “then you might think that, yes, this food might be important,” she said.

Tobacco use remains the leading preventable cause of cancer incidence and death worldwide. After tobacco, the lifestyle trio of diet, weight control and exercise may be linked to one-third to two-thirds of cancers. “They’re inseparable,” Neuhouser said. “You can have a great diet and you can have a healthy weight, but if you’re extremely sedentary then there’s a risk.”And there’s a strong link between excess weight and several kinds of cancer, including the esophagus, breast (after menopause), endometrium, colon and rectum, kidney, pancreas, thyroid, gallbladder, according to the NCI. 

Evidence mounts about how lifestyle may affect risk of cancer. In the largest study of its kind, nearly half a million Americans were evaluated for adherence to American Cancer Society cancer prevention guidelines that include smoking avoidance; a healthful, consistent weight; physical activity; limiting alcohol; and a diet emphasizing plants.

Those who followed the guidelines most closely had lowered risk of developing cancer (10 percent for men, 19 percent for women) and dying from cancer (25 percent for men, 24 percent for women) compared with those whose habits were least in line with the guidelines. Most striking was the reduction of overall risk of dying: 26 percent for men, 33 percent for women during the 14-year study period.

Fourteen types of cancer seemed affected by lifestyle behavior, most particularly gallbladder, endometrial, liver and colorectal. For men and women, a healthful weight and physical activity were the top factors in reduced deaths overall. Albert Einstein College of Medicine Researchers published this analysis online in January in the American Journal of Clinical Nutrition, based on data from a National Institutes of Health/AARP study.

Another approach to cancer and nutrition considers dietary patterns. “What we eat on any one day is not going to change our cancer risk, but it’s the pattern over the long term.” Neuhouser said. Several diets that emphasized fruit, vegetables, whole grains and plants or plant-based proteins were analyzed against information collected over more than 12 years from nearly 64,000 post-menopausal women in the Women’s Health Initiative Observational Study. Consuming a high-quality diet was associated with lower death rates from chronic diseases including cancer, as reported last year in the American Journal of Epidemiology.

The bacteria, viruses and other organisms that live in and on humans seem to play a bigger role in health and disease than was previously understood, Freudenheim said. How the countless microbes in such areas as the gut and the mouth might contribute to or prevent cancers is one of the open questions in the new area of study of the microbiome, which refers to the many organisms in the body, 10 percent of which are human and 90 percent nonhuman.

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Further reasons to be cautious of using antibiotics, and more support for finding beneficial bacteria and other microbes to outcompete the "bad" microbes. I especially liked the last paragraph that stressed for a healthy microbiota (microbial community):"Instead of trying to kill the "bad" bacteria causing an illness, a healthy and functioning microbiota may be able to outcompete the unwanted microbes and improve immune function." From Medical Xpress:

Unwanted impact of antibiotics broader, more complex than previously known

Researchers at Oregon State University have discovered that antibiotics have an impact on the microorganisms that live in an animal's gut that's more broad and complex than previously known. The findings help to better explain some of the damage these medications can do, and set the stage for new ways to study and offset those impacts.

Researchers have known for some time that antibiotics can have unwanted side effects, especially in disrupting the natural and beneficial microbiota of the gastrointestinal system. But the new study helps explain in much more detail why that is happening, and also suggests that powerful, long-term antibiotic use can have even more far-reaching effects. Scientists now suspect that antibiotic use, and especially overuse, can have unwanted effects on everything from the immune system to glucose metabolism, food absorption, obesity, stress and behavior.

The issues are rising in importance, since 40 percent of all adults and 70 percent of all children take one or more antibiotics every year, not to mention their use in billions of food animals. Although when used properly antibiotics can help treat life-threatening bacterial infections, more than 10 percent of people who receive the medications can suffer from adverse side effects.

This research used a "cocktail" of four antibiotics frequently given to laboratory animals, and studied the impacts."Prior to this most people thought antibiotics only depleted microbiota and diminished several important immune functions that take place in the gut," Morgun said. "Actually that's only about one-third of the picture. They also kill intestinal epithelium. Destruction of the intestinal epithelium is important because this is the site of nutrient absorption, part of our immune system and it has other biological functions that play a role in human health."

The research also found that antibiotics and antibiotic-resistant microbes caused significant changes in mitochondrial function, which in turn can lead to more epithelial cell death....Mitochondria plays a major role in cell signaling, growth and energy production, and for good health they need to function properly.

Morgun and Schulzhenko's research group also found that one of the genes affected by antibiotic treatment is critical to the communication between the host and microbe. "When the host microbe communication system gets out of balance it can lead to a chain of seemingly unrelated problems," Morgun said. Digestive dysfunction is near the top of the list, with antibiotic use linked to such issues as diarrhea and ulcerative colitis. But new research is also finding links to obesity, food absorption, depression, immune function, sepsis, allergies and asthma.

Healthy microbiota may also be another way to address growing problems with antibiotic resistance, Morgun said. Instead of trying to kill the "bad" bacteria causing an illness, a healthy and functioning microbiota may be able to outcompete the unwanted microbes and improve immune function.

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This is very interesting, and raises all sorts of possibilities for microbial transplants. While it's looking at only one person, this seems to be evidence that microbes are involved with our weight and manipulating them may result in weight gain or loss. From Science Daily:

Rapid and unexpected weight gain after fecal transplant

A woman successfully treated for a recurrent Clostridium difficile infection with stool from an overweight donor rapidly gained weight herself afterwards, becoming obese, according to a case report published in the new journal Open Forum Infectious Diseases.

Fecal microbiota transplant (FMT) is a promising treatment for relapsing C. difficile infections, a common cause of antibiotic-related diarrhea that in severe cases may be life-threatening. The case suggests that clinicians should avoid selecting stool donors who are overweight. The report also raises questions about the role of gut bacteria in metabolism and health.

At the time of the woman's fecal transplant in 2011, her weight was stable at 136 pounds, and her Body Mass Index (BMI) was 26. Then 32 years old, she had always been of normal weight. The transplant used donor stool from the woman's overweight but otherwise healthy teenage daughter, administered via colonoscopy, to restore a healthy balance of bacteria in the woman's gut, curing her C. difficile infection.

Sixteen months later, the woman weighed 170 pounds, and her BMI was 33, meeting medical criteria for obesity. The weight gain persisted despite a medically supervised liquid protein diet and exercise program. Continuing efforts to diet and exercise did not lower her weight: Three years after the transplant, she weighed 177 pounds with a BMI of 34.5, and she remains obese today.

"We're questioning whether there was something in the fecal transplant, whether some of those 'good' bacteria we transferred may have had an impact on her metabolism in a negative way," said Colleen R. Kelly, MD, of the Warren Alpert Medical School of Brown University, who wrote the case report with Neha Alang, MD, of Newport Hospital in Rhode Island. Such a link between bacteria in the gastrointestinal tract and weight is supported by previously published animal studies, where transfer of gut bacteria from obese to normal-weight mice can lead to a marked increase in fat. In light of the case and the animal data, the authors recommend selecting stool donors who are not overweight for fecal transplants.

Importantly, the FMT was not the only possible cause of the woman's weight gain. In addition to treatment for C. difficile, she had also been treated with several antibiotics for Helicobacter pylori infection. Other possible contributing factors in the woman's weight gain include the resolution of her C. difficile infection, genetic factors, aging, and stress related to illness. However, as noted above, she had never been overweight before.