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Tag: gut microbiota

Published on Leave a comment on Early Research Says No Benefit to Probiotics For Healthy Adults

Many probiotic manufacturers say that their product has all sorts of wonderful health benefits in people eating that particular probiotic, but is the evidence there? Finally, now there is a review of the best existing studies looking at whether probiotics have any effect on the gut bacteria of healthy, normal individuals. In other words, are the probiotics even staying there (to have some beneficial effect) or do they just "pass through" without leaving anything behind?

The main finding: only one study out of 7 found any lasting effect on gut microbes (in healthy individuals) from the probiotics which had been ingested daily over varying times, but typically for one month. Note: RCTs are randomly controlled trials, which are the best way to test whether something has an effect - because people are randomly assigned to a group. In these studies no one knew who was getting a placebo (e.g., received capsule without the probiotic) or the probiotic (e.g., in the capsule) - this eliminates self-selection and bias. But perhaps the bacteria strains tested were the wrong ones? Or the time period wasn't long enough or the bacteria weren't given in sufficient amounts? Also, studies didn't test multi-strain probiotics (which people commonly take), but only 1 or 2 species of bacteria.

However, other research has shown benefits from probiotics in individuals with "dysbiosis" (microbial communities out of whack) or certain illnesses. It'll be interesting to see what further research finds. These are still early days in this research. From MedicalXpress:

Do probiotics have an effect on healthy adults? It's too early to tell

There is little evidence to support any consistent effect of probiotics on the gut microbiota of healthy individuals, according to a systematic review published in the open access journal Genome Medicine. The World Health Organization defines probiotics as live microorganisms which confer a health benefit to the host if administered in adequate amounts and probiotics products are often marketed toward the general population. However, evidence for their effects on bacteria living in the guts of healthy adults remains elusive.

The study by researchers at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen is a systematic review of seven randomized controlled trials (RCTs) investigating the effect of probiotic products on the fecal microbiota of healthy adults.

Nadja Buus Kristensen, PhD student and junior author, said: "According to our systematic review, no convincing evidence exists for consistent effects of examined probiotics on fecal microbiota composition in healthy adults, despite probiotic products being consumed to a large extent by the general population."...The authors found that of the seven original RCTs included in the study, only one observed significantly greater changes in the bacterial species composition of the fecal microbiota in individuals who consumed probiotics compared to those who did not.

Also, an international consensus on what defines a normal or healthy fecal microbial community is lacking....Study participants across the seven original RCTs included in this review were healthy adults between 19 and 88 years of age. Numbers of individuals ranged from 21 to 81 and the proportion of women was between 50 and 100%. Probiotic products were administered as biscuits, milk-based drinks, sachets, or capsules for periods of 21 to 42 days.

Oluf Pedersen, professor at the University of Copenhagen and senior author of the paper said: "While there is some evidence from previous reviews that probiotic interventions may benefit those with disease-associated imbalances of the gut microbiota, there is little evidence of an effect in healthy individuals. 

Published on Leave a comment on Childhood Antibiotic Use Disrupts Gut Microbiome

This confirms what researchers such as Dr. Martin Blaser (in his book Missing Microbes) and others (such as Drs. Sonnenburg and Sonnenburg) have been saying about antibiotic use in infants and children: that there are negative effects to the gut microbiome from antibiotic use in early childhood, and the more frequent the use, the greater the negative effects. It is because the use of antibiotics  in early childhood "disrupts the microbiome".

Penicillins appear to be less disruptive, but macrolides (e.g., Clarithromycin, azithromycin) much more disruptive - the researchers found that the gut microbiota recovered within 6–12 months after a penicillin course, but did not fully recover from a macrolide course even after 2 years . Antibiotics can be life-saving, but they absolutely should not be used casually because there are hidden costs (such as microbiome changes). From Medical Xpress:

Antibiotic use in early life disrupt normal gut microbiota development

The use of antibiotics in early childhood interferes with normal development of the intestinal microbiota, shows research conducted at the University of Helsinki. Particularly the broad-spectrum macrolide antibiotics, commonly used to treat respiratory tract infections, have adverse effects. Macrolides appear also to contribute to the development of antibiotic-resistant strains of bacteria.  ...continue reading "Childhood Antibiotic Use Disrupts Gut Microbiome"

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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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I mentioned these studies earlier in July, but this write-up (from Sept. 17, 2014) gives the reader some new information. From Gut Microbiota Watch:

Studies uncover 500 “hidden” microbes in the gut

Over the last few years, scientists have found that the microbes hosted in the digestive tract (the gut microbiota or gut flora) perform key functions for health. Digestion, immunity and even mental health are extremely dependent on tasks carried out by the gut bacteria.

Now, two studies have found that the human gut hosts five hundred species of microbes – and seven million microbial genes – that were unknown until now. The proportion of the gut flora that had been hidden until now may hold essential information on the origin of a range of diseases (IBD and metabolic syndrome, among others), as well as the clues on how to cure them.

The two studies were published in Nature Biotechnology in July, and come from the efforts of the MetaHIT(METAgenomics of the Human Intestinal Tract) project, a European consortium working to explore the composition of human gut microbiota.

The first of the two studies focuses on expanding the catalogue of genes that belong to microbes of the gut flora....As a result, the catalogue has increased to 10 million genes. The next step for the scientists is to find what these genes do, in order to have a better understanding of the functions performed by the microbiota.

The second of the two studies pursues an even more ambitious goal: identifying new organisms in the microbiota, rather than identifying new genes....By applying this method, the authors have found 500 species whose existence in the microbiota was previously unknown.

Interestingly, some of the subjects analysed in the study had very few of these new species. By checking who these individuals were, the authors found that they all had Crohn’s disease, ulcerative colitis, or metabolic syndrome with an inflammatory component. These findings suggest that there is a correlation between suffering from these diseases and having less diversity in these unknown species. “These species, unknown until now, will possibly make the difference between healthy and unhealthy people”, said Guarner.

This information may open the door to new strategies aimed at recovering the presence of these species through nutritional intervention. In particular, providing patients with probiotics or prebiotics,  that may help to balance their microbiota.

Published on

More long-standing medical advice goes out the window. New advice: avoid diet soda and artificial sweeteners. The amazing part is that our gut bacteria are involved.

From Science Daily: Certain gut bacteria may induce metabolic changes following exposure to artificial sweeteners

Artificial sweeteners -- promoted as aids to weight loss and diabetes prevention -- could actually hasten the development of glucose intolerance and metabolic disease, and they do so in a surprising way: by changing the composition and function of the gut microbiota -- the substantial population of bacteria residing in our intestines. These findings, the results of experiments in mice and humans, ...says that the widespread use of artificial sweeteners in drinks and food, among other things, may be contributing to the obesity and diabetes epidemic that is sweeping much of the world.

For years, researchers have been puzzling over the fact that non-caloric artificial sweeteners do not seem to assist in weight loss, with some studies suggesting that they may even have an opposite effect.

Next, the researchers investigated a hypothesis that the gut microbiota are involved in this phenomenon. They thought the bacteria might do this by reacting to new substances like artificial sweeteners, which the body itself may not recognize as "food." Indeed, artificial sweeteners are not absorbed in the gastrointestinal tract, but in passing through they encounter trillions of the bacteria in the gut microbiota.

The researchers treated mice with antibiotics to eradicate many of their gut bacteria; this resulted in a full reversal of the artificial sweeteners' effects on glucose metabolism. Next, they transferred the microbiota from mice that consumed artificial sweeteners to "germ-free," or sterile, mice -- resulting in a complete transmission of the glucose intolerance into the recipient mice. This, in itself, was conclusive proof that changes to the gut bacteria are directly responsible for the harmful effects to their host's metabolism.... A detailed characterization of the microbiota in these mice revealed profound changes to their bacterial populations, including new microbial functions that are known to infer a propensity to obesity, diabetes, and complications of these problems in both mice and humans.

Does the human microbiome function in the same way? Dr. Elinav and Prof. Segal had a means to test this as well. As a first step, they looked at data collected from their Personalized Nutrition Project (www.personalnutrition.org), the largest human trial to date to look at the connection between nutrition and microbiota. Here, they uncovered a significant association between self-reported consumption of artificial sweeteners, personal configurations of gut bacteria, and the propensity for glucose intolerance. They next conducted a controlled experiment, asking a group of volunteers who did not generally eat or drink artificially sweetened foods to consume them for a week, and then undergo tests of their glucose levels and gut microbiota compositions.

The findings showed that many -- but not all -- of the volunteers had begun to develop glucose intolerance after just one week of artificial sweetener consumption. The composition of their gut microbiota explained the difference: the researchers discovered two different populations of human gut bacteria -- one that induced glucose intolerance when exposed to the sweeteners, and one that had no effect either way. Dr. Elinav believes that certain bacteria in the guts of those who developed glucose intolerance reacted to the chemical sweeteners by secreting substances that then provoked an inflammatory response similar to sugar overdose, promoting changes in the body's ability to utilize sugar.

This image depicts gut microbiota. Credit: Weizmann Institute of Science

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The following is from a presentation from The American Association of Diabetes Educators Annual Meeting August 6-9, 2014 by M.Jardin and C.Kafity. But the coffee and tea statement is different from what I've read elsewhere, specifically that coffee is beneficial, is a source of soluble fiber, and may keep pathogenic bacteria in check. From Endocrinology Today:

Plant-based diet helps grow healthy microbiota, halt diabetes disease process

With research mounting on the onslaught the body’s microbiota take from human eating patterns and the environment, making choices to maintain inner ecosystem health is essential, according to presenters at the American Association of Diabetes Educators Annual Meeting. Choosing a plant-based diet is one way people can increase the diversity of bacteria in their biome, reduce inflammation and begin to reverse the diseases processes involved in obesity and diabetes — often in just a few days.

“We know obesity and diabetes have increased tremendously in the last 20 years and we know that our genes haven’t changed, so that can’t account for the change,” Meghan Jardine, MS, MBA, RD, LD, CDE, RDN, of Parkland Health and Hospital System, said during a presentation. “Many scientists believe the changes in our diet and physical activity can’t really account for the change either, that there’s something else at work here.”

Weighing at least two kilograms in all and accounting for more than 3 times the amount of the body’s human cells, gut bacteria is colonized after birth, stabilized by age 3 years but influenced by a number of external factors, Jardine explained. Areas of influence include nutrition and immune function, both priorities in treating obesity and diabetes.

“Microbiota releases enzymes that digest food so we can absorb nutrients, produces vitamins, combats opportunistic infections and works with the immune system,” Jardine said. “About 70% of our immune systems are in our gut.”

People who consume plant-based diets have “healthy” gut microbiota in terms of global parameters and functional and compositional features, Christina Kafity, RN, BSN,CHC... “Children and elderly individuals who consumed more plant carbohydrates versus the typical standard American diet had rapid, reproducible alterations of the gut microbiota for the better, and this happened within 24 hours to a week,” Kafity said.

Growing good bacteria depends on creating an environment in which they can thrive, Kafity explained, including choosing foods that contain certain fibers intact in plants and probiotics; among them are soluble, insoluble and functional fibers as well as psyllium and inulin.

Intake of cruciferous vegetables including Brussels sprouts, kale and cabbage can help boost healthy microbes and, further, provide glucosinolates to help to reduce inflammation, Kafity said. Yogurt, kefir and probiotics also promote the growth of good bacteria, Kafity noted, while some popular beverages may not be much help. “We’re considering that coffee and teas may actually sterilize the bacteria.”

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New discoveries of what is going on in our intestines, plus a new vocabulary to understand it all. Yes, it all is amazingly complex. Bottom line: we have complex communities (bacteria, bacterial viruses or bacteriophages, etc.) living and interacting in our intestines. And only with state-of-the-art genetic analysis (DNA sequencing) can we even "see" what is going on. I highlighted really important items in bold type. From Medical Xpress:

Researchers uncover new knowledge about our intestines

Researchers from Technical University of Denmark Systems Biology have mapped 500 previously unknown microorganisms in human intestinal flora as well as 800 also unknown bacterial viruses (also called bacteriophages) which attack intestinal bacteria.

"Using our method, researchers are now able to identify and collect genomes from previously unknown microorganisms in even highly complex microbial societies. This provides us with an overview we have not enjoyed previously," says Professor Søren Brunak who has co-headed the study together with Associate Professor Henrik Bjørn Nielsen.

So far, 200-300 intestinal bacterial species have been mapped. Now, the number will be more than doubled, which could significantly improve our understanding and treatment of a large number of diseases such as type 2 diabetes, asthma and obesity.

The two researchers have also studied the mutual relations between bacteria and viruses. Previously, bacteria were studied individually in the laboratory, but researchers are becoming increasingly aware that in order to understand the intestinal flora, you need to look at the interaction between the many different bacteria found.

And when we know the intestinal bacteria interactions, we can potentially develop a more selective way to treat a number of diseases. "Ideally we will be able to add or remove specific bacteria in the intestinal system and in this way induce a healthier intestinal flora," says Søren Brunak.

From Science Daily:

Revolutionary approach to studying intestinal microbiota

Analyzing the global genome, or the metagenome of the intestinal microbiota, has taken a turn, thanks to a new approach to study developed by an international research team. This method markedly simplifies microbiome analysis and renders it more powerful. The scientists have thus been able to sequence and assemble the complete genome of 238 intestinal bacteria, 75% of which were previously unknown. 

Research carried out in recent years on the intestinal microbiota has completely overturned our vision of the human gut ecosystem. Indeed, from "simple digesters" of food, these bacteria have become major factors in understanding certain diseases such as obesity, type 2 diabetes, or Crohn's disease. Important and direct links have also been demonstrated between these bacteria and the immune system, as well as with the brain. It is estimated that 100,000 billion bacteria populate the gut of each individual (or 10 to 100 times more than the number of cells in the human body), and their diversity is considerable, estimated to around a thousand different bacterial species in the intestinal human metagenome. However, because only 15% of these bacteria were previously isolated and characterized by genome sequencing, an immense number of the microbial genes previously identified still need to be assigned to a given species.

An analysis of 396 stool samples from Danish and Spanish individuals allowed the researchers to cluster these millions of genes into 7381 co-abundance groups of genes. Approximately 10% of these groups (741) corresponded to bacterial species referred to as metagenomic species (MGS); the others corresponded to bacterial viruses (848 bacteriophages were discovered), plasmids (circular, bacterial DNA fragments) or genes which protected bacteria from viral attack (known as CRISPR sequences). 85% of these MGS constituted unknown bacteria species (or ~630 species).

Using this new approach, the researchers succeeded in reconstituting the complete genome of 238 of these unknown species, without prior culture of these bacteria. Living without oxygen, in an environment that is difficult to characterise and reproduce, most of these gut bacteria cannot be cultured in the laboratory. 

The authors also demonstrated more than 800 dependent relationships within the 7381 gene co-abundance groups; this was the case, for example, of phages which require the presence of a bacterium to survive. These dependent relationships thus enable a clearer understanding of the survival mechanisms of a micro-organism in its ecosystem. 

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The study talked specifically about 3 types of bacteria that were different among the groups (severely obese, diabetics, healthy) studied: Firmicutes, Bifidobacteria, Clostridium leptum. From Science Daily:

Gut microbe levels are linked to type 2 diabetes and obesity

People with Type 2 diabetes or obesity have changes in the composition of their intestinal micro-organisms -- called the gut microbiota -- that healthy people do not have, researchers from Turkey have found.

The study lends support to other recent reports that have found an association between specific bacterial species in the human digestive system and obesity and diabetes, according to lead investigator Yalcin Basaran, MD, an endocrinologist from Gulhane Military Medical Academy School of Medicine, Ankara, Turkey.

The human digestive system contains an estimated 10 trillion to 100 trillion bacteria and other microscopic organisms, with each person housing at least 160 different species of organisms, according to Basaran. 

Basaran and his fellow researchers sought to identify the relationship between the gut microbe composition and obesity and Type 2 diabetes. Their study included 27 severely obese adults (20 men and seven women) whose body mass index, or BMI, exceeded 35 kg/m2, as well as 26 adults (18 men and eight women) with newly diagnosed Type 2 diabetes and 28 healthy control subjects (22 men and six women). 

Fecal analysis using a molecular biology technique showed that several of the most common types of bacteria in the gut were present at considerably lower levels in the obese and diabetic groups, compared with healthy controls. These reductions ranged from 4.2 to 12.5 percent in the obese patients and 10 to 11.5 percent in the diabetic patients, Basaran reported.

"Manipulation of intestinal bacteria could offer a new approach to manage obesity and Type 2 diabetes."

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A big benefit to exercising - more microbial diversity, which means a healthier gut microbiome, which means better health. From Medscape:

Exercise Linked to More Diverse Intestinal Microbiome

Professional athletes are big winners when it comes to their gut microflora, suggesting a beneficial effect of exercise on gastrointestinal health, investigators report in an article published online June 9 in Gut.

DNA sequencing of fecal samples from players in an international rugby union team showed considerably greater diversity of gut bacteria than samples from people who are more sedentary.

Having a gut populated with myriad species of bacteria is thought by nutritionists and gastroenterologic researchers to be a sign of good health. Conversely, the guts of obese people have consistently been found to contain fewer species of bacteria, note Siobhan F. Clarke, PhD, from the Teagasc Food Research Centre, Moorepark, Fermoy. "Our findings show that a combination of exercise and diet impacts on gut microbial diversity. In particular, the enhanced diversity of the microbiota correlates with exercise and dietary protein consumption in the athlete group," the authors write.

The investigators used 16S ribosomal RNA amplicon sequencing to evaluate stool and blood samples from 40 male elite professional rugby players (mean age, 29 years) and 46 healthy age-matched control participants. 

Relative to control participants with a high BMI, athletes and control participants with a low BMI had improved metabolic markers. In addition, although athletes had significantly increased levels of creatine kinase, they also had overall lower levels of inflammatory markers than either of the control groups.

Athletes were also found to have more diverse gut microbiota than controls, with organisms in approximately 22 different phyla, 68 families, and 113 genera. Participants with a low BMI were colonized by organisms in just 11 phyla, 33 families, and 65 genera, and participants with a high BMI had even fewer organisms in only 9 phyla, 33 families, and 61 genera.

The professional rugby players, as the investigators expected, had significantly higher levels of total energy intake than the control participants, with protein accounting for 22% of their total intake compared with 16% for control participants with a low BMI and 15% for control participants with a high BMI. When the authors looked for correlations between health parameters and diet with various microbes or microbial diversity, they found significant positive association between microbial diversity and protein intake, creatine kinase levels, and urea.