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A number of recent studies have suggested that as people age, the community of gut microbes (gut microbiota or gut microbiome) becomes less diverse than in younger people. And note that greater gut microbial diversity is generally viewed as healthy and good. However, now a study done in China finds a different result. The study examined the gut microbes of more than 1000 very healthy people, from ages 3 to over 100, and found that the gut microbial communities were very similar among very healthy people in their mid 30s to over 100 years in age.

Whether this is cause or effect is unknown. But the researchers speculate that the similarities in the gut microbiota among people from their 30s to 100+ is a consequence of an active healthy lifestyle and diet. And it suggests that somehow changing an elderly person's gut microbial community (if it's not "normal") to that of a 30-year-old might help promote health. From Science Daily:

'Ridiculously healthy' elderly have the same gut microbiome as healthy 30-year-olds

In one of the largest microbiota studies conducted in humans, researchers at Western University, Lawson Health Research Institute and Tianyi Health Science Institute in Zhenjiang, Jiangsu, China have shown a potential link between healthy aging and a healthy gut.

With the establishment of the China-Canada Institute, the researchers studied the gut bacteria in a cohort of more than 1,000 Chinese individuals in a variety of age-ranges from 3 to over 100 years-old who were self-selected to be extremely healthy with no known health issues and no family history of disease. The results showed a direct correlation between health and the microbes in the intestine. ....The study, published this month in the journal mSphere, showed that the overall microbiota composition of the healthy elderly group was similar to that of people decades younger, and that the gut microbiota differed little between individuals from the ages of 30 to over 100.

"The main conclusion is that if you are ridiculously healthy and 90 years old, your gut microbiota is not that different from a healthy 30 year old in the same population," said Greg Gloor, the principal investigator on the study and also a professor at Western's Schulich School of Medicine & Dentistry and Scientist at Lawson Health Research Institute. Whether this is cause or effect is unknown, but the study authors point out that it is the diversity of the gut microbiota that remained the same through their study group.

"This demonstrates that maintaining diversity of your gut as you age is a biomarker of healthy aging, just like low-cholesterol is a biomarker of a healthy circulatory system," Gloor said. The researchers suggest that resetting an elderly microbiota to that of a 30-year-old might help promote health. "By studying healthy people, we hope to know what we are striving for when people get sick," said Reid. [Original study.]

Centenarian in Bama County, China. Credit: National Geographic.

Mediterranean Diet is Healthy Eating – A Good Option for Seniors An article was just published in a research journal to discuss the fact that humans - in part due to lifestyles which include less dietary fiber (due to eating fewer varieties and amounts of plants) and due to medical practices (such as frequent use of antibiotics) has resulted in gut "bacterial extinctions". In other words, humans (especially those living an urban industrialized Western lifestyle) have fewer gut bacterial species than those living a more traditional lifestyle, and this loss of bacterial species is linked to various diseases. Humans can increase the number of certain bacterial species, but the loss of some bacterial species is forever. 

The researchers discuss that humans have the "lowest level of gut bacterial diversity"  of any hominid and primate. They stated that the shrinking of the variety of microbial species in the human gut (the gut microbiome) began early in human evolution (as humans started eating more meat), but that it has accelerated dramatically within industrialized societies. And that evidence is accumulating that this gut bacterial "depauperation" - the loss of a variety of bacterial species - may predispose humans to a range of diseases.  Some of it is due to evolution (as humans ate more meat), and some to lifestyle changes. A term is used throughout this paper: depauperate - which means lacking in numbers or variety of species in the gut microbiome (the microbial community or ecosystem).

Other research has also shown that eating a highly processed Western diet results in gut microbial changes that are linked to various diseases (here, here, here) - that is, the microbes being fed are those associated with diseases. Also, certain diets encourage certain microbial species to flourish (here, here).  Bottom line: studies find health benefits from higher levels of dietary fiber - from fruits, vegetables, seeds, nuts, whole grains, and legumes (beans). From Current Opinion In Microbiology:

The shrinking human gut microbiome

Highlights: Humans harbor the lowest levels of gut bacterial diversity of any hominid. Humans in industrialized nations harbor fewer gut bacterial taxa than any primate. Medical practices and lack of dietary fiber may drive gut bacterial extinctions. Depauperate microbiotas may predispose entire human populations to certain diseases.

Mammals harbor complex assemblages of gut bacteria that are deeply integrated with their hosts’ digestive, immune, and neuroendocrine systems. Recent work has revealed that there has been a substantial loss of gut bacterial diversity from humans since the divergence of humans and chimpanzees. This bacterial depauperation began in humanity’s ancient evolutionary past and has accelerated in recent years with the advent of modern lifestyles. Today, humans living in industrialized societies harbor the lowest levels of gut bacterial diversity of any primate for which metagenomic data are available, a condition that may increase risk of infections, autoimmune disorders, and metabolic syndrome. Some missing gut bacteria may remain within under-sampled human populations, whereas others may be globally extinct and unrecoverable.

A typical human harbors on the order of 1013 bacterial cells in the large intestine. This gut microbiota, which can contain over a thousand species, is deeply integrated with virtually every tissue and organ system in the body. Gut bacteria process difficult to digest components of the diet, promote angiogenesis in the intestine, train the immune system, regulate metabolism, and even influence moods and behaviors.

In contrast to hunter–gatherer to agricultural transitions, adoptions of industrial and post-industrial lifestyles have led to massive reductions in bacterial richness within human gut microbiotas. Individuals living in urban centers in the United States harbor fewer gut bacterial species on average than do individuals living more traditional lifestyles in Malawi , Venezuela, Peru, and Papua New Guinea.....Industrialized and traditional lifestyles differ in many respects, confounding the identification of the specific practices that have led to decreases in gut bacterial diversity within industrialized societies. One potential cause is the rise of food processing and the corresponding reductions in the intake of dietary fiber in favor of simple sugars. Recently, studies in model systems have indicated that long-term reductions in dietary fiber can lead to the extirpation of gut bacterial taxa from host lineages. 

Other potential causes of reduced gut bacterial diversity within industrialized human populations include certain modern medical practices. For example, longitudinal studies in humans have shown that levels of gut bacterial diversity decrease drastically after antibiotic use. Although bacterial richness may recover after treatment is completed, the timeline and extent of the restoration is highly subject-dependent. The consequences of antibiotic use on gut bacterial diversity may be most severe when treatment is administered during the early years of life, before the adult microbiota has fully formed .

 A new study found differences in gut microbes between active women (they exercised at least the recommended amount) and those that are sedentary. When the gut bacteria were analyzed with modern tests (genetic sequencing) the active women had more of the health promoting beneficial bacteria such as Faecalibacterium prausnitzii, Roseburia hominis, and Akkermansia muciniphila than the sedentary women. The sedentary women also had some bacterial species not seen in the active women. The researchers said that exercise "modifies the composition of gut microbiota" (the gut microbes) in a way beneficial for health.

And what is the recommended minimal amount of exercise? The World Health Organization recommends at least 3 days of exercise per week for 30 minutes at a moderate intensity. Note that exercise can mean doing exercises, but it can also include walking briskly, intense housework (scrubbing, vacuuming with lots of bending, etc.), gardening (digging, raking, etc), or shoveling snow, etc. In this study the group of active women had at least 3 hours of physical exercise per week. Note that a sedentary lifestyle is associated with a high incidence of chronic diseases such as cardiovascular disease, cancer and diabetes, while physical exercise or activity has metabolic and immune health benefits (prevents disease).

But...reading the full study, the research also showed that the active group ate more fruits and vegetables - which we know has an effect on the gut microbiome and feeds beneficial bacteria. Although the diets of the 2 groups of women were similar in total carbohydrates, protein and fat content eaten, the active women ate more fruits, vegetables, and fiber, and the sedentary group ate more processed meat. So it looks like both exercise and a good amount of fruits and vegetables may be important for nurturing beneficial bacteria. By the way, the 3 species of beneficial bacteria mentioned currently are not found in any probiotic supplements on the market. (Earlier posts on the beneficial F. prausnitzii and Akkermansia muciniphila). From PLoS ONE:

Differences in gut microbiota profile between women with active lifestyle and sedentary women

Physical exercise is a tool to prevent and treat some of the chronic diseases affecting the world’s population. A mechanism through which exercise could exert beneficial effects in the body is by provoking alterations to the gut microbiota, an environmental factor that in recent years has been associated with numerous chronic diseases. Here we show that physical exercise performed by women to at least the degree recommended by the World Health Organization can modify the composition of gut microbiota. Using high-throughput sequencing of the 16s rRNA gene, eleven genera were found to be significantly different between active and sedentary women. Quantitative PCR analysis revealed higher abundance of health-promoting bacterial species in active women, including Faecalibacterium prausnitzii, Roseburia hominis and Akkermansia muciniphila. Moreover, body fat percentage, muscular mass and physical activity significantly correlated with several bacterial populations. In summary, we provide the first demonstration of interdependence between some bacterial genera and sedentary behavior parameters, and show that not only does the dose and type of exercise influence the composition of gut microbiota, but also the breaking of sedentary behavior.

Sedentary lifestyle is associated with a high incidence of chronic diseases such as cardiovascular disease, cancer and diabetes. Physical exercise is a powerful preventative and treatment intervention that is known to be effective in generating metabolic and immune health benefits. The gut microbiota is essential for processing dietary components and has a major role in shaping the immune system.... Dysbiosis or imbalance in gut microbiota has been associated with many diseases, among which are ulcerative colitis, Crohn's disease, colon cancer, metabolic syndrome, type I and type II diabetes, cardiovascular disease, allergy, asthma, eczema and autism.....Several studies in experimental models have addressed the relationship between gut microbiota composition and physical exercise....Collectively, these findings indicate that modulation of the microbiota by exercise depends not only on the physiological state of the individual, but also on the diet.

A total of 15 phyla were detected, in order of presence: Bacteroidetes (54%), Firmicutes (44%), Proteobacteria (0.96%), Tenericutes (0.39%), Verrucomicrobia (0.11%), Euryarchaeota (0.08%), Actinobacteria (0.07%), Lentisphaerae (0.06%), Cyanobacteria (0.050%), Spirochaetes (0.04%), Fusobacteria (0.014%), Elusimicrobia (0.009%), Synergistetes (0.007%), kTM7 (0.003%), and Acidobacteria (0.0001%). Acidobacteria (2 subjects), Elusimicrobia (2 subjects) and Spirochaetes (2 subjects) phyla were detected only in sedentary subjects.... At the genus level, there were significant differences in eleven genera: Bifidobacterium, Barnesiellaceae, Odoribacter, Paraprevotella, Turicibacter, Clostridiales, Coprococcus, Ruminococcus, and two unknown genera of Ruminococcaceae family. Given the importance of some bacterial species in health, the presence of Bifidobacterium longum, Faecalibacterium prausnitzii, Roseburia hominis, Akkermansia muciniphila was measured by qPCR. Analyses revealed a more significant abundance of F. prautznnii, R. hominis and A. muciniphila in active than in sedentary women.

Among all the genera studied, the abundance of eleven of them was significantly different between the active and sedentary group, with Paraprevotella and an unclassified genus of the Desulfovibrionaceae family specifically associated with sedentarism parameters, while the remaining genera where largely associated with diet parameters.....Nonetheless, as exercise and diet often go hand in hand, an active lifestyle is frequently associated with a high consumption of fruits and vegetables, whereas sedentarism is associated with the consumption of high-calorie and fatty foods. Indeed, exercise interventions in human populations have resulted in an improvement in diet habits. Although the diets were similar in our study regarding total carbohydrates, protein and fat content, significant differences were observed for fiber (higher in the active group) and processed meat (higher in the sedentary group).

What things in our environment have an effect on the microbes living within us? We now know that gut microbes are important for our health in many ways, and that thousands of species of bacteria, as well as viruses, fungi, and other microbes normally live in a healthy person's gut. We refer to these microbes as the human microbiota or human microbiome. When the community of gut microbes is thrown out of whack (dysbiosis) there can be a number of negative health effects, including diseases. Researchers are just learning about all the microbes within us and their importance in health and disease. [See all posts on the human microbiome.]

Past posts have discussed such things as antibiotics, emulsifiers, different foods and diets, heartburn drugs, etc. having an effect on the human microbiome, but what else? A recent study from China reviewed some environmental pollutants and their effects on gut microbiota - as shown in both human and animal studies. They reviewed studies on antibiotics, heavy metals (arsenic, cadmium, lead), persistant organic pollutants or POPs (organochlorine pesticides, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers, and polycyclic aromatic hydrocarbons or PAHs), pesticides (permethrin, chlorpyrifos, pentachlorophenol, epoxiconazole and carbendazim, imazalil), emulsifiers, nanoparticles (e.g., silver nanoparticles), and artificial sweeteners. They found that all these environmental pollutants had effects on gut microbes - with some effects lasting for years. Their conclusion: gut microbes are very sensitive to drugs, diet, and environmental pollutants. By the way, notice that popular food ingredients such as emulsifiers and artificial sweeteners were considered "environmental pollutants" by the researchers.

Excerpts from Environmental Pollution: Effects of environmental pollutants on gut microbiota

Environmental pollutants have become an increasingly common health hazard in the last several decades. Recently, a number of studies have demonstrated the profound relationship between gut microbiota and our health. Gut microbiota are very sensitive to drugs, diet, and even environmental pollutants. In this review, we discuss the possible effects of environmental pollutants including antibiotics, heavy metals, persistent organic pollutants, pesticides, nanomaterials, and food additives on gut microbiota and their subsequent effects on health. We emphasize that gut microbiota are also essential for the toxicity evaluation of environmental pollution. In the future, more studies should focus on the relationship between environmental pollution, gut microbiota, and human health.

Thousands of species are found in the gut microbiome, and the majority of these species belong to six bacterial phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia (Eckburg et al., 2005). Gut microbiota are highly dynamic and have substantial interindividual and intraindividual variation....The gut microbiota are very essential for host health. They participate in the regulation of many physiological functions. The gut microbiota reside in our intestinal mucus layer and even participate in shaping the mucus layer (Jakobsson et al., 2015). They help us to digest food (such as fiber); synthesize vitamins and amino acids (Spanogiannopoulos et al., 2016); play very important roles in energy metabolism and storage, immune system modulation, growth, and neurodevelopment; and can even regulate our behavior.... The occurrence of many diseases is correlated with altered gut microbiome composition (Lange et al., 2016). Gut microbiota dysbiosis is considered to be a potential cause of obesity (Cani et al., 2007; Fei and Zhao, 2013). However, gut microbiota are very sensitive to drugs, diet, and environmental pollutants.

Although most environmental pollutants do not directly target gut microbiota, some pollutants can enter the body and interact with the gut microbiota through different pathways. A number of previous studies have shown that exposure to environmental pollutants can alter the composition of the gut microbiome, leading to disorders of energy metabolism, nutrient absorption, and immune system function or the production of other toxic symptoms (Jin et al., 2015c; Zhang et al., 2015b). In the present review, we conclude that different kinds of environmental pollutants can induce gut microbiota dysbiosis and have multiple potential adverse effects on animal health

Heavy metals in the environment have become a severe health risk in recent years (Liu et al., 2016a). As a common form of environmental pollution, heavy metals are associated with a wide range of toxic effects, including carcinogenesis, oxidative stress, and DNA damage, and effects on the immune system..... Recently, several studies have stated that heavy metal exposure could also lead to gut microbiota dysbiosis, indicating that study of gut microbiota provides a new approach to analyze the mechanisms of heavy metal toxicity

Immune system function is tightly coupled to our gut microbiome. Gut microbiota and their metabolites can interact with both the innate immune system and the adaptive immune system (Honda and Littman, 2016; Thaiss et al., 2016).... Alterations in the gut microbiome can disrupt the balance between the host immune system and gut microbiota, induce immune responses, and even trigger some immunological diseases. Furthermore, immune system imbalance may influence the microbiota metabolites. For example, trimethylamine, which is absorbed from food by gut microbiota, can induce atherosclerosis (Chistiakov et al., 2015).

 For years it has been known that most children with autism spectrum disorder (ASD) have all sorts of gastrointestinal (GI) problems (e.g., constipation, diarrhea, stomach pain, food intolerance), and the more severe the autism, the more severe the GI problems. Recent studies suggested that a major factor in this are abnormal gut bacteria, with the gut microbial community out of whack (dysbiosis). Previous studies looking at the gut microbiome of children with autism have shown lower diversity and lower amounts (abundances) of certain bacteria in children with autism compared to neurologically normal (neurotypical) children.

A recent study of children with autism spectrum disorder found that giving the children a fecal microbiota transplant (FMT) led to significant and lasting improvements in both gastrointestinal (GI) symptoms and autism-related behaviors and symptoms. A fecal microbiota transplant (FMT) is a transplant of fecal matter from a healthy donor to the recipient. A fecal microbial transplant contains approximately a thousand bacterial species that live in a healthy gut, as well as other microbes such as viruses and fungi. FMTs have so far been an amazingly successful treatment for recurrent Clostridium difficile infections, and are now being looked at as promising treatments of chronic inflammatory diseases such as inflammatory bowel disease.

The researchers were surprised to see an 80% improvement in gastrointestinal symptoms, especially abdominal pain, indigestion, diarrhea, and constipation. They also saw about a 25% improvement in autism related behaviors and symptoms which persisted for 8 weeks after treatment stopped, which is when the study ended. One measurement of adaptive behaviors (such as communication, daily living skills, and socialization) found that the average developmental age increased by 1.4 years after treatment. The researchers also found that there was a "rebalancing" of the gut microbes following treatment. They found evidence of "successful partial engraftment of donor microbiota and beneficial changes in the gut environment" - meaning they could see that donor microbes were living in the gut. Also, overall bacterial diversity increased (which is good) and the abundance of certain bacteria increased (including Bifidobacterium, Prevotella, and Desulfovibrio), and these changes persisted until the end of the study.

The researchers caution that this was a small trial, that there could be placebo effects, and so the results should be "cautiously interpreted and viewed as preliminary." But nonetheless, the results are exciting. Really exciting. From Science Daily:

Autism symptoms improve after fecal transplant, small study finds

Children with autism may benefit from fecal transplants -- a method of introducing donated healthy microbes into people with gastrointestinal disease to rebalance the gut, a new study has found. Behavioral symptoms of autism and gastrointestinal distress often go hand-in-hand, and both improved when a small group of children with the disorder underwent fecal transplant and subsequent treatment. In the study of 18 children with autism and moderate to severe gastrointestinal problems, parents and doctors said they saw positive changes that lasted at least eight weeks after the treatment. Children without autism were included for comparison of bacterial and viral gut composition prior to the study.

Previous research has established that children with autism typically have fewer types of some important bacteria in their guts and less bacterial diversity overall -- a difference that held true in this study. That could be because many of them are prescribed a lot of antibiotics in the first three years of life, the research team wrote in the study.

Parents of the children not only reported a decrease in gut woes including diarrhea and stomach pain in the eight weeks following the end of treatment: They also said they saw significant changes for the better when it came to behavioral autism symptoms in their sons and daughters, who ranged from 7 to 16 years old....One of those tools showed the average developmental age increased by 1.4 years after treatment. 

Researchers also were able to document a rebalancing of the gut following treatment. At the end of the study, the bacterial diversity in the children with autism was indistinguishable from their healthy peers. The study also included a unique viral analysis by Ohio State scientists, made possible because of previous work in the world's oceans. Gregory, who is particularly interested in the interplay between viruses and bacteria, used genetic testing to examine the viral diversity in the guts of the treated children. It rebounded quickly, and became more similar to the donor's microbiome. "Those donor viruses seemed to help," she said.

Fecal transplantation is done by processing donor feces and screening it for disease-causing viruses and bacteria before introducing it into another person's gastrointestinal tract. In this study, the researchers used a method called microbiota transfer therapy, which started with the children receiving a two-week course of antibiotics to wipe out much of their existing gut flora. Then, doctors gave them an initial high-dose fecal transplant in liquid form. In the seven to eight weeks that followed, the children drank smoothies blended with a lower-dose powder[Original study.]

 An earlier post discussed how emulsifiers (which are added to most processed foods to aid texture and extend shelf life) can alter the the community of microbes that live in our gut (gut microbiota) in such a way as to cause intestinal inflammation. Now the same researchers found that regular consumption of emulsifiers alter intestinal bacteria in a manner that promotes low-grade intestinal inflammation and possibly colorectal cancer.

The emulsifiers used in the study were the commonly used carboxymethylcellulose and polysorbate-80, but some others are soy lecithin, carrageenan, and polyglycerol ester. Processed foods often contain several emulsifiers, and while food regulations limit the amount of each emulsifier present in a particular food product to 1% to 2%, they don’t restrict the number of emulsifiers allowed. The study was done in mice, but the researchers tried to model the level of exposure of humans who eat a lot of processed food. From Science Daily:

Common food additive promotes colon cancer in mice

Emulsifiers, which are added to most processed foods to aid texture and extend shelf life, can alter intestinal bacteria in a manner that promotes intestinal inflammation and colorectal cancer, according to a new study. The findings, published in the journal Cancer Research, show regular consumption of dietary emulsifiers in mice exacerbated tumor development....There is increasing awareness that the intestinal microbiota, the vast, diverse population of microorganisms that inhabits the human intestines, play a role in driving colorectal cancer.

The microbiota is also a key factor in driving Crohn's disease and ulcerative colitis, the two most common forms of inflammatory bowel disease (IBD). IBD is known to promote colon tumorigenesis and gave rise to the term "colitis-associated cancer." Low-grade inflammation, a condition more prevalent than IBD, was shown to be associated with altered gut microbiota composition and metabolic disease and is observed in many cases of colorectal cancer. These recent findings suggest dietary emulsifiers might be partially responsible for this association.

Previous reports by the Georgia State research team suggested that low-grade inflammation in the intestine is promoted by consumption of dietary emulsifiers, which are detergent-like molecules incorporated into most processed foods that alter the composition of gut microbiota. The addition of emulsifiers to food seems to fit the time frame and had been shown to promote bacterial translocation across epithelial cells. Viennois and Chassaing hypothesized that emulsifiers might affect the gut microbiota in a way that promotes colorectal cancer. They designed experiments in mice to test this possibility.

In this study, the team fed mice with two very commonly used emulsifiers, polysorbate 80 and carboxymethylcellulose, at doses seeking to model the broad consumption of the numerous emulsifiers that are incorporated into the majority of processed foods. Researchers observed that consuming emulsifiers drastically changed the species composition of the gut microbiota in a manner that made it more pro-inflammatory, creating a niche favoring cancer induction and development. Alterations in bacterial species resulted in bacteria expressing more flagellin and lipopolysaccharide, which activate pro-inflammatory gene expression by the immune system.

 Many of us grew up having silver colored dental fillings (called dental amalgam) in our teeth. Dental amalgam has been used for over 150 years for the treatment of dental cavities (caries) because it is durable, easy to use, and affordable. But it is composed of about 50% elemental mercury (Hg) and so it may release a certain amount of mercury both during the time the cavity is filled and afterward with normal wear. Mercury can cause adverse health effects, such as effects on the central nervous system, kidneys, and immune system. Human mercury exposure also occurs through the consumption of mercury (MeHg) contaminated seafood.

Recently many dentists switched to the use of the composite resins, which are mercury-free alternative materials. However, these can release can release small quantities of bisphenol A (BPA) when applied and as they degrade in the mouth. BPA is an endocrine disruptor, has been found to cause various adverse health effects, including reproductive effects, and can be measured in urine. Which raised the question, do persons with composite resin fillings have elevated BPA in their bodies?

This study examined 14,703 subjects who were divided into three groups based on the number of dental surface restorations (DSR): 0, 1–8, or greater than 8. Dental surface restorations applies to fillings, and not crowns. Note that a tooth's surface can have 5 surfaces (in molars and pre-molars), so 8 filled surfaces can be fewer than 8 teeth with fillings. (It's not the number of fillings, but the surface area they occupy - so the Science Daily article title is misleading.)

They found that the more dental surface restorations a person has, the higher the levels of mercury in the blood. But they found no association between dental surface restorations and urinary BPA. These results are reassuring for those with fillings made of composite resins, but not for people with fillings of dental amalgam. Note: DSR are Dental Surface Restorations, THg is blood total mercury, IHG is inorganic mercury, and MeHg is methyl mercury (typically from seafood). From Science Daily:

Have more than eight dental fillings? It could increase the mercury levels in your blood

Dental surface restorations composed of dental amalgam, a mixture of mercury, silver, tin and other metals, significantly contribute to prolonged mercury levels in the body, according to new research from the University of Georgia's department of environmental health science in the College of Public Health.This research, which analyzed data from nearly 15,000 individuals, is the first to demonstrate a relationship between dental fillings and mercury exposure in a nationally representative population.

The researchers further analyzed exposure by specific types of mercury and found a significant increase in methyl mercury, the most toxic form of mercury, related to dental fillings. Yu said this result suggests the human gut microbiota, a collection of microorganisms living in the intestines, may transform different types of mercury.

Dental amalgam has been the go-to dental filling material for more than 150 years, because it's affordable and durable. However, about half of the compound contains mercury, a heavy metal known to be toxic at high levels, causing brain, heart, kidney, lung and immune system damage. New research suggests that methyl mercury may cause damage even at low levels.

"As toxicologists, we know that mercury is poison, but it all depends on the dose. So, if you have one dental filling, maybe it's OK. But if you have more than eight dental filings, the potential risk for adverse effect is higher," Yu said....The results show that individuals with more than eight fillings had about 150 percent more mercury in their blood than those with none. The average American has three dental fillings, while 25 percent of the population has 11 or more fillings.

The study also looked at dental composite resins, a mercury-free alternative for dental fillings that can release small amounts of bisphenol A, or BPA, which may cause developmental or reproductive damage. The results found no association between dental fillings and urinary BPA, but further research is needed to understand BPA exposure from resin-based materials.

From the original study in :  Associations of blood mercury, inorganic mercury, methyl mercury and bisphenol A with dental surface restorations in the U.S. population, NHANES 2003–2004 and 2010–2012

Elevated mercury in urine usually indicates exposure to an elemental or inorganic source of mercury, while elevated mercury in blood usually indicates exposure to organic mercury or recent exposure to a high level of elemental mercury vapor. However, our current study found that THg, MeHg, and IHg significantly increased with the number of the DSRs after the adjustment of covariates. It is well established that inorganic mercury is released into circulation from amalgam restorations (Lorscheider et al., 1995); it is also widely believed that the only source of the organic form, methyl mercury, is from fish in the diet. However, accumulating evidence demonstrates that human oral or gut commensal bacteria can methylate mercury....Leistevuo et al. found a correlation between the total amalgam surfaces and organic mercury in saliva, suggesting both methylating and nonmethylating bacteria can enhance the formation of toxic methylmercury (Leistevuo et al., 2001).

Conclusions: We have found that dental surface restorations significantly contributed to the blood concentrations of THg and IHg in both periods of study, as well as MeHg in 2011–2012, after adjusting covariates such as age, education, race/ethnicity, gender, smoking, and fish consumption history. However, no association between the dental fillings and urinary BPA was found. This is the first study to demonstrate the relationship between dental fillings and body level of Hg and /or BPA in a nationally representative population. Our findings did not address the potential adverse health effects at low thresholds of mercury exposure; however, a significant correlation between the blood level of mercury and dental restoration raises major concerns about potential mercury exposure. 

 Another view of  type 2 diabetes - that the gut microbiome is involved, specifically two gut bacteria: Prevotella copri and Bacteroides vulgatus. View them as the bad guys. The researchers point out "... the majority of overweight and obese individuals are insulin resistant and it is well known that dietary shifts to less calorie-dense eating and increased daily intake of any kind of vegetables and less intake of food rich in animal fat tend to normalize imbalances of gut microbiota and simultaneously improve insulin sensitivity of the host." In other words, eat more vegetables and fewer calories (if you're overweight or obese) to improve the gut microbes. This is similar to yesterday's post of research that viewed type 2 diabetes as "a response to overnutrition" and potentially reversible. From Medical Express:

Gut bacteria imbalance increases diabetes risk

Currently, scientists think the major contributors to insulin resistance are excess weight and physical inactivity, yet ground-breaking new research by an EU funded European-Chinese team of investigators called MetaHit have discovered that specific imbalances in the gut bacteria can cause insulin resistance, which confers an increased risk of health disorders like type 2 diabetes.

We show that specific imbalances in the gut microbiota are essential contributors to insulin resistance, a forerunner state of widespread disorders like type 2 diabetes, hypertension and atherosclerotic cardiovascular diseases, which are in epidemic growth," says Professor Oluf Pedersen, Metabolism Center, University of Copenhagen, and senior lead author of the paper.

In the Danish study of 277 non-diabetic individuals and 75 type 2 diabetic patients, there was close collaboration between the University of Copenhagen and the Technical University of Denmark with extensive international participation from a team of investigators, who performed analyses of the action of the insulin hormone. They monitored the concentrations of more than 1200 metabolites in blood and did advanced DNA-based studies of hundreds of bacteria in the human intestinal tract to explore if certain imbalances in gut microbiota are involved in the causation of common metabolic and cardiovascular disorders.

The researchers observed that people who had a decreased capacity of insulin action, and therefore were insulin resistant, had elevated blood levels of a subgroup of amino acids called branched-chain amino acids (BCAAs). Importantly, the rise of BCAAs levels in blood was related to specific changes in the gut microbiota composition and function.

The main drivers behind the gut bacterial biosynthesis of BCAAs turned out to be the two bacteria Prevotella copri and Bacteroides vulgatus. To test mechanistically if gut bacteria were a true cause of insulin resistance, the researchers fed mice with the Prevotella copri bacteria for 3 weeks. Compared with sham fed mice the Prevotella copi fed mice developed increased blood levels of BCAAs, insulin resistance and intolerance to glucose.

"Most people with insulin resistance do not know that they have it. However, it is known that the majority of overweight and obese individuals are insulin resistant and it is well known that dietary shifts to less calorie-dense eating and increased daily intake of any kind of vegetables and less intake of food rich in animal fat tend to normalize imbalances of gut microbiota and simultaneously improve insulin sensitivity of the host," adds Pedersen. (Original study)

 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

 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.

It is already known that early-life use of antibiotics is connected to increased risk of immune-mediated diseases such as inflammatory bowel disease, and asthma, as well as obesity. The effect is thought to be mediated by the intestinal microbes, since antibiotics in animal studies has been found to change the composition of the intestinal microbiota and reduce biodiversity.

The study, conducted at the University of Helsinki and led by Professor Willem de Vos, included 142 Finnish children, aged 2 to 7 years. Researchers investigated how many courses of antibiotics the children had received in their lifetime and how the use of antibiotics was reflected in their intestinal microbiota. In addition, they investigated the association between use of antibiotics and asthma and body mass index. The study is published in the scientific journal Nature Communications.

The results showed that children's intestinal microbiota composition clearly reflected the use of antibiotics. Antibiotics reduced the bacterial species richness and slowed the age-driven microbiota development. Particularly the microbiota of the children who had received macrolide antibiotics, such as azithromycin or clarithromycin, within the past two years differed from normal. The less time had passed since the macrolide course, the larger were the anomalies in the microbiota.

"In general, it seems that the gut microbiota recovery from antibiotic treatment lasts more than a year. If a child gets repeated courses of antibiotics during their first years, the microbiota may not have time to fully recover", says the researcher, Katri Korpela, whose doctoral thesis project includes the newly published research.

Macrolides appear to promote also the development of antibiotic resistance, as the resistance to these antibiotics was elevated in the microbiota of children who had used them."Penicillin-type antibiotics seemed to have a weaker impact on the composition and functioning of the microbiome than macrolides", Korpela says. The results support the recommendation to avoid macrolides as the primary antibiotic, and generally restrict the use of antibiotics to genuine need. Antibiotics should not be used to treat self-limiting infections and never 'just in case', the researchers emphasize.