GIT

[Jo Bowyer]

Long-Term Green Tea Supplementation Does Not Change the Human Gut Microbiota

http://journals.plos.org/plosone/art...l.pone.0153134

Abstract

Background

Green tea catechins may play a role in body weight regulation through interactions with the gut microbiota.

Aim

We examined whether green tea supplementation for 12 weeks induces changes in composition of the human gut microbiota.

Methods

58 Caucasian men and women were included in a randomized, placebo-controlled design. For 12 weeks, subjects consumed either green tea (>0.56 g/d epigallocatechin-gallate + 0.28 ∼ 0.45 g/d caffeine) or placebo capsules. Fecal samples were collected twice (baseline, vs. week 12) for analyses of total bacterial profiles by means of IS-profiling, a 16S-23S interspacer region-based profiling method.

Results

No significant changes between baseline and week 12 in subjects receiving green tea or placebo capsules, and no significant interactions between treatment (green tea or placebo) and time (baseline and week 12) were observed for body composition. Analysis of the fecal samples in subjects receiving green tea and placebo showed similar bacterial diversity and community structures, indicating there were no significant changes in bacterial diversity between baseline and week 12 in subjects receiving green tea capsules or in subjects receiving placebo capsules. No significant interactions were observed between treatment (green tea or placebo) and time (baseline and week 12) for the gut microbial diversity. Although, there were no significant differences between normal weight and overweight subjects in response to green tea, we did observe a reduced bacterial alpha diversity in overweight as compared to normal weight subjects (p = 0.002).

Conclusion

Green tea supplementation for 12 weeks did not have a significant effect on composition of the gut microbiota.

How Green Tea Extract Could Help Protect Against Alzheimer’s

http://neurosciencenews.com/green-te...zheimers-7724/

Research from McMaster University is shedding new light on those underlying mechanisms. Preclinical evidence suggests that the green tea compound known as EGCG interferes with the formation of toxic assemblies (oligomers), one of the prime suspects in the early steps of the molecular cascade that leads to cognitive decline in Alzheimer’s patients.

“At the molecular level, we believe EGCG coats toxic oligomers and changes their ability to grow and interact with healthy cells,” explains Giuseppe Melacini, lead author and a professor in the Departments of Chemistry and Chemical Biology as well as of Biochemistry and Biomedical Sciences at McMaster, who has worked on Alzheimer’s-related research for 15 years.

The findings, which are the results of a decade of advancements in nuclear magnetic resonance (NMR) methodology and are featured in the cover page of the Journal of the American Chemical Society, could lead to new therapies and further drug discovery, say researchers.

Despite decades of research, the causes of Alzheimer’s remain not fully understood, and treatment options are limited. According to the latest census numbers, seniors living in Canada now outnumber children, dramatically increasing the need for effective drugs and prevention. By some estimates, the number of Canadians with dementia is expected to rise to 937,000 by the year 2031, an increase of 66 per cent compared to current numbers.

“We all know that currently there is no cure for Alzheimer’s once symptoms emerge, so our best hope is early intervention. That could mean using green tea extracts or their derivatives early on, say 15 to 25 years before any symptoms ever set in” says Melacini.

[Jo Bowyer]

Can more fiber restore microbiome diversity?

https://www.sciencedaily.com/release...0411133952.htm

"The idea to boost fiber levels is not new," says Jens Walter of the University of Alberta, Canada. "However, depletion of the microbiome adds a new perspective to this low-fiber Western diet that we are currently eating."

Earlier this year, Stanford University's Justin Sonnenburg found that mice fed a typical Western diet (high in fat and carbohydrates and low in fiber) transferred a lower diversity of beneficial microbial species to future generations. The re-introduction of the microbes' preferred fiber at that stage did not result in a return of some (good) species, indicating that extinctions had occurred in only a few generations.

Walter and co-author Edward Deehan, his PhD student, are concerned that a dramatic shift away from a diet similar to the one under which the human-microbiome symbiosis evolved is a key factor in the rise of non-communicable disorders like obesity.

"There is a lot of epidemiological evidence that fiber is beneficial, and food products containing dietary fiber have FDA-approved health claims for both colon cancer and coronary heart disease. There is also quite a bit of clinical evidence (although it is less consistent)," Walter says. "The most pressing issue at the moment that neither consumption of fiber in society nor the doses used in clinical research are high enough."

Walter has noticed that often researchers evaluating fiber doses in diets and health outcomes do so with "doses of fiber that [he] would consider physiologically irrelevant. Most of these studies use 5-15 grams of fiber; I would not think that these amounts would be actually beneficial," he says.

People living in non-industrialized societies have an average intake of fiber that is much higher than the low norms of Western societies. The authors note the recent work from the Stephen J.D. O'Keefe lab in Nature Communications (doi:10.1038/ncomms7342) in which modern African-Americans were given a traditional South-African diet that contained 55 grams of daily dietary fiber and had improved markers for colon cancer within two weeks.

In their Commentary, the authors propose a concerted effort by scientists, food producers, policy makers, and regulatory groups to address the fiber gap. They emphasize that clinical assessments of different fiber types and fiber-enriched foods on microbiome outcomes are needed.

Jens Walter also asserts that the challenge of restoring diverse gut inhabitants will be best met with regulatory policies that are specific to food, and not just the same as those for drugs. "To have a regulatory environment that makes it extremely hard to obtain health claims for food substances is very detrimental," says Walter. He is hopeful that regulatory policies will change to encourage innovative research on disease prevention by modulating the diverse microbial communities humans have evolved with and the ways our diet shapes them and by extension, all of us.

[Jo Bowyer]

Gut bacteria could help prevent cancer

https://www.sciencedaily.com/release...0413151108.htm

Researchers have shown that various types of intestinal bacteria might be factors in both causing and preventing obesity, and in other conditions and diseases. Now, a UCLA study suggests that it could also potentially be used to reduce the risk for some types of cancer.

The research, published online April 13 in the peer-reviewed journal PLOS ONE, offers evidence that anti-inflammatory "health beneficial" gut bacteria can slow or stop the development of some types of cancer.

Ultimately, doctors might be able to reduce a person's risk for cancer by analyzing the levels and types of intestinal bacteria in the body, and then prescribing probiotics to replace or bolster the amount of bacteria with anti-inflammatory properties, said Robert Schiestl, professor of pathology, environmental health sciences and radiation oncology at UCLA and the study's senior author.

"It is not invasive and rather easy to do," he said.

Schiestl and his colleagues isolated a bacterium called Lactobacillus johnsonii 456, which is the most abundant of the beneficial bacteria, and which has some pretty useful applications outside of medicine. "Since it is a Lactobacillus strain, it makes excellent yogurt, kefir, kombucha and sauerkraut."

In the UCLA study the bacterium reduced gene damage and significantly reduced inflammation -- a critical goal because inflammation plays a key role in many diseases, including cancer, neurodegenerative diseases, heart disease, arthritis and lupus, and in the aging process.

Cancer survivors get a taste for kefir after exercise

https://www.sciencedaily.com/release...0712110446.htm

Kefir may be a beneficial post-exercise beverage for cancer survivors. It means that cancer survivors can enjoy the nutritional support that milk provides without the potential for significant stomach upset, report researchers.

Update 13/07/2017

[Jo Bowyer]

Identification of Environmental Factors Associated with Inflammatory Bowel Disease in a Southwestern Highland Region of China: A Nested Case-Control Study

Abstract

Background

The aim of this study was to examine environmental factors associated with inflammatory bowel disease (IBD) in Yunnan Province, a southwestern highland region of China.

Methods

In this nested case-control study, newly diagnosed ulcerative colitis (UC) cases in 2 cities in Yunnan Province and Crohn’s disease (CD) cases in 16 cities in Yunnan Province were recruited between 2008 and 2013. Controls were matched by geography, sex and age at a ratio of 1:4. Data were collected using the designed questionnaire. Conditional logistic regression models were used to estimate adjusted odds ratios (ORs).

Results

A total of 678 UC and 102 CD cases were recruited. For UC, various factors were associated with an increased risk of developing UC: dietary habits, including frequent irregular meal times; consumption of fried foods, salty foods and frozen dinners; childhood factors, including intestinal infectious diseases and frequent use of antibiotics; and other factors, such as mental labor, high work stress, use of non-aspirin non-steroidal anti-inflammatory drugs and allergies (OR > 1, p < 0.05). Other factors showed a protective effect: such as consumption of fruits, current smoking, physical activity, and drinking tea (OR < 1, p < 0.05). For CD, appendectomy and irregular meal times increased the disease risk (OR >1, p < 0.05), whereas physical activity may have reduced this risk (OR < 1, p < 0.05).

Conclusions

This study is the first nested case-control study to analyze the association between environmental factors and IBD onset in a southwestern highland region of China. Certain dietary habits, lifestyles, allergies and childhood factors may play important roles in IBD, particularly UC.

PLOS ONE

[Jo Bowyer]

Worm infection counters inflammatory bowel disease by drastically changing gut microbiome

https://www.sciencedaily.com/release...0414145513.htm

Infection with worms counters inflammatory bowel diseases (IBD) by triggering immune responses that change the mix of bacteria, or microbiome, in the gut. This is according to a study published online April 14 in the journal Science.

The study results support the hygiene hypothesis which, in the case of IBD, argues that the absence of exposure to worms in too-clean modern living spaces has left some with oversensitive, gut-based immune systems vulnerable to inflammatory diseases. Gut worms have helped to train and balance immune systems throughout human evolution, but are now missing in developed nations, which, in turn, have the highest rates of Crohn's disease and ulcerative colitis.

[Jo Bowyer]

Oligosaccharides released from milk glycoproteins are selective growth substrates for infant-associated bifidobacteria

http://aem.asm.org/content/early/201...8/AEM.00547-16

ABSTRACT

Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast fed infant gut. Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. Here, EndoBI-1 was used to release these N-glycans from concentrated bovine colostrum at the pilot scale. EndoBI-1-released N-glycans supported the rapid growth of Bifidobacterium longum subsp. infantis, a species that grows well on human milk oligosaccharides, but did not support growth of Bifidobacterium animalis subsp. lactis, a species which does not. Conversely Bifidobacterium longum subsp. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction clearly demonstrating that the glycan portion of milk glycoproteins provides the key substrate for growth. Mass spectrometry-based profiling revealed that B. longum subsp. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. animalis subsp. lactis only degraded 11% of neutral and virtually no (<1%) sialylated N-glycans. These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-borne bifidobacteria capable of carrying out the initial deglycosylation. Moreover, released N-glycans are better growth substrates than the intact milk glycoproteins suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. Finally, the variety of N-glycans released from bovine milk glycoproteins suggests they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides.

IMPORTANCE Previously it was shown that glycoproteins serve as growth substrates for Bifidobacteria. However, which part of glycoprotein (glycans or polypeptides) is responsible for the function was not known. In this study, we used a novel enzyme to cleave conjugated N-glycans from milk glycoproteins and tested their consumption by various bifidobacteria. The results showed that the glycans selectively stimulate the growth of B.infantis, which is a key infant gut microbe. The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (Nano-LC-Chip-Q-TOF MS) to reveal that B. infantis can consume the range of released glycans structures from whey protein concentrate.

Molecular Insight into Evolution of Symbiosis between Breast-Fed Infants and a Member of the Human Gut Microbiome Bifidobacterium longum
http://www.cell.com/cell-chemical-bi...456(17)30095-8

Update 06/04/2016

[Jo Bowyer]

Association between Polycystic Ovary Syndrome and Gut Microbiota

Introduction

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in their reproductive years, affecting 5%-10% of women worldwide [1]. The syndrome is characterized by the presence of at least two of the three classical features: hyperandrogenism, oligo-/anovulation and polycystic ovaries on pelvic ultrasound [2]. Women with PCOS, particularly those with menstrual irregularities may have difficulties conceiving because of anovulation. Besides that, PCOS patients frequently have metabolic disturbances with cardiovascular, type II diabetes, dyslipidemia, visceral obesity and endothelial dysfunction risk factors [3–5]. Therefore, PCOS is not just a cosmetic and fertility problem but also a major health problem that could shorten women’s life expectancy.

The etiology and pathogenesis of PCOS remain unclear and may be multi-factorial, involving genetic, neuroendocrine and metabolic causes [6–9]. Some researchers believe that PCOS may be not an ovarian disease but a metabolic disorder disease [10]. Till now, there is not any unified theory for the pathophysiology of PCOS. What is consistent in PCOS is the production of excess androgens by the ovaries. Further studies are required to investigate the primary pathophysiology mechanisms underlying this syndrome.

Human gut harbors more than 100 trillion microbes referred to as the gut microbiota. However, in the past, the commensal microbiota was largely neglected and mostly inaccessible to investigation. Until recently, researchers realize that these residents in human gut form a symbiotic relationship with the host and provide many benefits to the host. For example, commensal microbes consistently provide a set of services to the host such as modulation of immune system, inhibition of pathogen colonization, liberating nutrients from food [11–13]. Meanwhile, dysbiosis of gut microbiota has been implicated in many disease states, including diabetes, obesity and cardiovascular disease [14–16].

Recently, a novel concept of “microgenderome” related to the potential bidirectional interaction roles between the sex hormones and gut microbiota has emerged [17]. It has been reported that the composition of commensal microbes of male and female animals diverged at the time of puberty, which implied that sex hormone levels exerted specific influences on the composition of the microbiota. Removal of gut microbiota increased the testosterone concentration in female mice but decreased the concentration in male mice. Thus, the commensal gut microbiota also had effects on the production of male sex hormone [18]. It is interesting to explore the role of gut microbiota in PCOS, as the androgen level in PCOS women always elevated. Tremellen and Pearce suggest that dysbiosis of gut microbiota (DOGMA) brought by a high fat-sugar diet in PCOS patients leads to an increase in the intestinal permeability. Lipopolysaccharide produced by gram negative bacteria traverses the “leaky gut” wall into the circulation, leading to a chronic state of low grade inflammation. The activation of immune system interferes with insulin receptor, driving up insulin level, which boosts testosterone production in the ovary leading to PCOS. The DOGMA theory can account for the role of gut microbiota in the pathogenesis of PCOS [19].

On these grounds, we hypothesize that excess androgen biosynthesis in PCOS may result in the dysbiosis of host gut microbiota and modulating of gut microbiota may be beneficial for PCOS treatment. In this study, in order to verify our hypotheses, PCOS rat model was established using letrozole induction. Microbiota interventions through Lactobacillus transplantation and fecal microbiota transplantation (FMT) from healthy rats were used for the treatments of PCOS rats. Administration of probiotics such as Lactobacillus is an attractive concept in combating various diseases. L rhamnosus GR-1 attenuated lipopolysaccharide-induced inflammation in pregnant CD-1 mice [20]. Lactobacillus acidophilus NCFM maintained insulin sensitivity in a metabolically heterogeneous group [21]. Lactobacillus rhamnosus GG and Lactobacillus casei DN-114-001 protected epithelial barrier function against Escherichia coli-induced redistribution of the tight-junction proteins [22, 23]. Fecal microbiota transplantation (FMT) was introduction of fecal suspension derived from a healthy donor into the gastrointestinal tract of a diseased individual. It has been proposed as a novel therapeutic approach to modulate gut microbiota dysbiosis. Patients with metabolic syndrome increased insulin sensitivity after infusion of microbiota from lean donors [24]. Our previous study showed that FMT promoted the re-establishment of intestinal microbial communities and mucosal barriers in mice with antibiotic-induced dysbiosis [25]. Thus, the available animal and human evidences suggested that Lactobacillus transplantation and FMT could serve as new therapies for treating diseases. In the present study, after microbiota interventions through Lactobacillus transplantation and FMT, the estrous cycles, sex hormonal levels, ovarian morphology and gut microbiota were examined. We hope that our results will shed a new light on the pathogenesis and treatment for PCOS.

PLOS ONE

[Jo Bowyer]

Microbial cooperation in the intestine

http://www.nature.com/nature/journal...ture17626.html

The human intestine is home to a dense and diverse ecosystem of microbes, but little is known about how the abundant bacteria in our gut interact with each other. In a new study published in Nature this week, Brigham and Women's Hospital (BWH) investigators, in collaboration with colleagues at Boston Children's Hospital, report on a rare example of cooperation between different species of bacteria.

The team found that one species of bacteria, Bacteroides ovatus, digests a dietary polysaccharide -- a complex carbohydrate -- at a cost to itself but at a benefit to another species. Using in vitro experiments and a mouse model, the team found that B. ovatus receives reciprocal benefits from other gut species in return.

"Finding a predominant member of our microbiota that doesn't need to digest a dietary sugar in order to use it for itself, but that seems to be doing so to feed another species of bacteria was a big surprise," said lead author Seth Rakoff-Nahoum, MD PhD, of Boston Children's Hospital's Division of Infectious Diseases.

"Such interspecies cooperative interactions are rarely described, especially among the abundant bacteria in our intestines," said senior author Laurie Comstock, PhD, of BWH's Division of Infectious Diseases.

[Jo Bowyer]

Lifestyle has a strong impact on intestinal bacteria, which has a strong impact on health

https://www.sciencedaily.com/release...0428151853.htm

Everything you eat or drink affects your intestinal bacteria, and is likely to have an impact on your health. That is the finding of a large-scale study led by RUG/UMCG geneticist Cisca Wijmenga into the effect of food and medicine on the bacterial diversity in the human gut, which is published this Friday in the research journal Science.

In this study researchers collected stool samples from more than 1100 people taking part in the LifeLines programme, which is monitoring the health of 165,000 residents of the Northern Netherlands. The samples were used to analyze the DNA of the bacteria and other organisms that live in the gut. In addition to stools, the study collected information on the participants' diet, medicine-use and health.

This study is unique in that it focused on a group of normal people whereas previous research was frequently focused on patients with a specific illness. Further, the study covered an exceptionally large group of people and studied their gut DNA in detail. "Normally researchers only investigate one particular region of DNA in which different groups of bacteria can be distinguished," Wijmenga explains. "We have mapped all the bacterial DNA to gain much more detailed information about bacteria types."

Coffee and wine

This DNA analysis made it possible to examine which factors impact the diversity of the microbiome (the intestinal bacterial community unique to each of us). And that appears to be many. Wijmenga says, "You see, for example, the effect of diet in the gut." People who regularly consume yogurt or buttermilk have a greater diversity of gut bacteria. Coffee and wine can increase the diversity as well, while whole milk or a high-calorie diet can decrease it.

"In total we found 60 dietary factors that influence the diversity. What these mean exactly is still hard to say," explains UMCG researcher Alexandra Zhernakova, the first author of the Science article. "But there is a good correlation between diversity and health: greater diversity is better."

Beyond diet, at least 19 different kinds of medicine -- some of which are widely used -have an impact on microbiome diversity. An earlier study by Groningen researchers has shown that antacids decrease this diversity, while antibiotics and the diabetes drug metformin also have an effect. These are important findings Wijmenga stresses, "Disease often occurs as the result of many factors. Most of these factors, like your genes or your age, are not things you can change. But you can change the diversity of your microbiome through adapting your diet or medication. When we understand how this works, it will open up new possibilities."

Stool samples

Recent research has demonstrated the importance of this. It is now possible to combat obesity through a 'fecal transplantation' in which the intestinal bacteria from a slender person are introduced into the gut of an obese patient. An appropriate diet or a specific medicine may produce the same effect on the microbiome.

Currently a lot of research is looking into the microbiome, but it often seems hard to reproduce. It is therefore striking that the results of a Belgian group published in the same issue of Science show about 80 percent agreement with those of the Groningen group. "The key is the way the research was done," Wijmenga says. What was important was that the stool samples were frozen immediately by the participants themselves, and picked up by the researchers while still frozen. "When samples are sent in by post, as is often the case, you expose them to oxygen and high temperatures. These are conditions that some bacteria can't survive in. These two Science articles have therefore set a new standard for future research in this field."

[Jo Bowyer]

'Bugs' as drugs: Harnessing novel gut bacteria for human health

https://www.sciencedaily.com/release...0504141127.htm

Scientists at the Wellcome Trust Sanger Institute have grown and catalogued more than 130 bacteria from the human intestine according to a study published in Nature today (Wednesday May 4, 2016).

The researchers have developed a process to grow the majority of bacteria from the gut, which will enable scientists to understand how our bacterial 'microbiome' helps keep us healthy. Imbalances in our gut microbiome can contribute to complex conditions and diseases such as obesity, Inflammatory Bowel Disease, Irritable Bowel Syndrome and allergies. This research will allow scientists to start to create tailor-made treatments with specific beneficial bacteria.

Research in this field has expanded greatly in recent years with the intestinal microbiome being termed a 'forgotten organ', such is its importance to human health. Approximately 2 per cent of a person's body weight is due to bacteria. Many of these bacteria are sensitive to oxygen and are difficult to culture in the laboratory, so until now it has been extremely difficult to isolate and study them.

Hilary Browne, based in the Host-Microbiota Interactions Laboratory, at the Wellcome Trust Sanger Institute, explains: "It has become increasingly evident that microbial communities play a large role in human health and disease. By developing a new process to isolate gastrointestinal bacteria, we were able to sequence their genomes to understand more about their biology. We can also store them for long periods of time making them available for further research."

Antibiotics wipe out our gut bacteria -- killing both the pathogen targets and the beneficial bacteria too. There is then the potential for less desirable bacteria, such as those with antibiotic resistance, to repopulate the gut faster than the beneficial bacteria, leading to further health issues, such as Clostridium difficile infection.

Current treatment for C. difficile infection can involve transplants of faeces from healthy people, to repopulate the gut. However this treatment is far from ideal. Using the library of new bacteria, Dr Trevor Lawley and his team at the Sanger Institute are hoping to create a pill, containing a rationally selected, defined mix of bacteria, which could be taken by patients and replace faecal transplants.

Dr Sam Forster from the Sanger Institute and Hudson Institute of Medical Research in Australia said: "The extensive database of genomes we have generated from these bacteria is also essential for studying which bacteria are present or absent in people with gastrointestinal conditions. Now we can start to design mixtures of therapeutics candidates for use in these diseases."

For the first time, the researchers also looked at the proportion of bacteria that form spores within the gut. Spores are a form of bacterial hibernation allowing some bacteria to remain dormant for long periods of time. They found approximately one third of the gut microbiota from a healthy person produced spores that allow bacteria to survive in the open air and potentially move between people. This provides a means of microbiota transmission that has not been considered before and could imply that health and certain diseases could be passed, not just through human genetics, but also via the microbiome.

Dr Trevor Lawley, group leader at the Sanger Institute said: "Being able to cast light on this microbial 'Dark matter' has implications for the whole of biology and how we consider health. We will be able to isolate the microbes from people with a specific disease, such as infection, cancers or autoimmune diseases, and study these microbes in a mouse model to see what happens. Studying our 'second' genome, that of the microbiota, will lead to a huge increase in our understanding of basic biology and the relationship between our gut bacteria and health and disease."

my italics

[Jo Bowyer]

A mother's breast milk supports immune responses in her newborn that help the infant's gut become a healthy home to a mix of bacterial species, thanks in part to newly identified antibodies from the m

https://www.sciencedaily.com/release...0506095828.htm

Scientists believe the gut is sterile and bacteria-free at birth, when suddenly the infant is exposed to bacteria from the wider world. The body learns to tolerate many bacterial species, and the relationship is regarded as mutually beneficial -- in exchange for free meals, gut bacteria aid digestion, help prevent infection and enhance immune function.

The new study sheds light on how immune antibodies from breast milk interact with the just-forming immune system of the newborn to help shape lifelong immune responses that are key for establishing boundaries and balance between gut microbes and the mammalian host. If this balance fails to become established or later falters, chronic inflammatory conditions, such as Crohn's disease or ulcerative colitis, may result.

A healthy relationship between host and bacteria is deemed to be "commensal," essentially meaning that neither is harmed.

There are other components in breast milk known to shape the composition of the gut microbiota. As evidence for a long and evolving relationship between mammals and gut microbes, scientists previously identified sugars in breast milk that commensal bacteria can derive energy from, but which are indigestible to the infant.

In addition, there are other molecules in breast milk, made by the mother's immune system, that promote tolerance for commensal microbes while keeping them in the gut and away from the rest of the body.

Barton said the distinctive immune responses by the newborn's immature immune system were "surprising." The researchers found that the antibody responses against the gut microbiota did not depend on arousing the T helper cells that are the foot soldiers of the evolutionarily advanced "adaptive" immune system, but instead relied on signaling by the earlier-evolved, innate immune system.

[Jo Bowyer]

The Stomach-Derived Hormone Ghrelin Increases Impulsive Behavior

http://www.nature.com/npp/journal/v4...p2015297a.html

INTRODUCTION

Impulsivity, defined as impaired decision making or action without foresight, is associated with many psychiatric and behavioral disorders such as attention-deficit/hyperactivity disorder, substance abuse, and eating disorders (Dawe and Loxton, 2004; Schag et al, 2013). Much remains to be discovered about the neurobiological mechanisms that govern impulsivity. Understanding factors that induce impulsive behavior can provide new therapeutic avenues for many impulsivity-associated psychiatric disorders. Major neurotransmitters, such as dopamine and serotonin, have been implicated in regulating impulsive behavior (Bizot et al, 1999; Eagle et al, 2009). Reduced dorsal striatal dopamine signaling at the dopamine 1 receptor (D1R) reduces impulsivity and at the dopamine 2 receptor (D2R) increases impulsivity (Eagle et al, 2011). Reduced central serotonin signaling increases impulsive action and choice in rats and pharmacological and optogenetic activation of dorsal raphe serotonin neurons reduces choice impulsivity (Harrison et al, 1997; Miyazaki et al, 2012, 2014). Interestingly both dopamine and serotonin are modulated by a stomach-produced hormone—ghrelin (Abizaid et al, 2006; Skibicka et al, 2013; Hansson et al, 2014)—however, the impact of ghrelin on impulsivity remains unexplored.

Ghrelin, a hormone produced in the stomach, is primarily recognized for its orexigenic role. Ghrelin levels increase before each meal that subsequently leads to the food intake (Cummings et al, 2004). The orexigenic action of ghrelin is primarily mediated by the growth hormone secretagogue receptors (GHSR) in the central nervous system. But ghrelin’s actions in the brain are not limited to control of basic food intake; ghrelin also increases reward behavior for food, alcohol, and other substances of abuse (Jerlhag et al, 2009; Skibicka et al, 2011a; Menzies et al, 2013). The impact of ghrelin on reward is thought to be mediated by dopamine and opioid signaling (Skibicka and Dickson, 2011, Skibicka et al, 2012, 2013). Food reward behavior has recently been shown to positively correlate with impulsivity (Velazquez-Sanchez et al, 2014). The impact of ghrelin on neurotransmitters critical for regulation of impulsive behavior, taken together with the regulatory role for ghrelin on food reward behavior (a behavior that correlates with impulsivity), led us to hypothesize that ghrelin’s neurobiological role could extend to the regulation of impulsivity.

Impulsivity is a heterogeneous construct and in its simplest form can be deconstructed into two components: impulsive action (motor disinhibition) and impulsive choice (impulsive decision making). In order to assess the role of ghrelin in impulsivity, three complementary rodent tests were used: differential reinforcement of low rate (DRL), go/no-go, and delay discounting. All three tests measure the ability to inhibit a behavioral response. While DRL and go/no-go measure impulsive action (the ability to restrain a response), delay discounting measures impulsive choice (the ability to defer gratification) (Bari and Robbins, 2013). The application of different tests in the current study allowed us to assess different aspects of impulsivity after ghrelin or a GHSR antagonist was infused into the lateral ventricle (LV). In order to further understand the neuroanatomical substrate underlying ghrelin’s impact on impulsivity, measured in the DRL task, ghrelin was also directly microinjected into the ventral tegmental area (VTA), an area harboring dopaminergic cell bodies of neurons projecting to, for example, the nucleus accumbens (NAc) and the orbitofrontal cortex (OFC). Finally, we measured dopamine turnover and the expression of genes previously associated with impulsivity in four brain nuclei strongly implicated in impulsivity control—the OFC, the dorsal striatum, the medial prefrontal cortex (mPFC), and the NAc (Bari and Robbins, 2013; Jupp et al, 2013).

[Jo Bowyer]

Healthy intestinal flora keeps the mind sharp — with some help from the immune system

http://scienmag.com/healthy-intestin...immune-system/

The gut and the brain “talk” to one another via hormones, metabolic products or direct neural connections. A specific population of monocyte immune cells acts as a further link between the two, as Dr. Susanne Wolf from the MDC research group led by Prof. Helmut Kettenmann recently discovered in collaboration with colleagues from the University of Magdeburg, the Charité – Universitätsmedizin Berlin, and the US National Institutes of Health (NIH).

The researchers switched off the gut microbiome in mice, i.e. their intestinal bacteria, with a strong concoction of antibiotics. Compared to the mice that had not undergone treatment, they subsequently observed significantly fewer newly formed nerve cells in the hippocampus region of the brain. The memory of the treated mice also deteriorated because the formation of these new brain cells – a process known as neurogenesis – is important for certain memory functions.

As well as impaired neurogenesis, the researchers also found that the population of a specific immune cell in the brain – the Ly6C(hi) monocytes – decreased significantly when the microbiota was switched off. Could these immune cells be a previously unknown intermediary between the two organ systems? Wolf and her team tested and confirmed this hypothesis: when they removed just these cells from the mice, neurogenesis declined and when they gave the cells to the mice that had been on antibiotics, neurogenesis increased once again.

from Simon Gandevia's twitter feed

[Jo Bowyer]

Intestinal Microbiota Is Influenced by Gender and Body Mass Index

http://journals.plos.org/plosone/art...l.pone.0154090

Abstract

Intestinal microbiota changes are associated with the development of obesity. However, studies in humans have generated conflicting results due to high inter-individual heterogeneity in terms of diet, age, and hormonal factors, and the largely unexplored influence of gender. In this work, we aimed to identify differential gut microbiota signatures associated with obesity, as a function of gender and changes in body mass index (BMI). Differences in the bacterial community structure were analyzed by 16S sequencing in 39 men and 36 post-menopausal women, who had similar dietary background, matched by age and stratified according to the BMI. We observed that the abundance of the Bacteroides genus was lower in men than in women (P<0.001, Q = 0.002) when BMI was > 33. In fact, the abundance of this genus decreased in men with an increase in BMI (P<0.001, Q<0.001). However, in women, it remained unchanged within the different ranges of BMI. We observed a higher presence of Veillonella (84.6% vs. 47.2%; X2 test P = 0.001, Q = 0.019) and Methanobrevibacter genera (84.6% vs. 47.2%; X2 test P = 0.002, Q = 0.026) in fecal samples in men compared to women. We also observed that the abundance of Bilophila was lower in men compared to women regardless of BMI (P = 0.002, Q = 0.041). Additionally, after correcting for age and sex, 66 bacterial taxa at the genus level were found to be associated with BMI and plasma lipids. Microbiota explained at P = 0.001, 31.17% variation in BMI, 29.04% in triglycerides, 33.70% in high-density lipoproteins, 46.86% in low-density lipoproteins, and 28.55% in total cholesterol. Our results suggest that gut microbiota may differ between men and women, and that these differences may be influenced by the grade of obesity. The divergence in gut microbiota observed between men and women might have a dominant role in the definition of gender differences in the prevalence of metabolic and intestinal inflammatory diseases.

[Jo Bowyer]

Abdominal Pain, the Adolescent and Altered Brain Structure and Function

http://journals.plos.org/plosone/art...l.pone.0156545

Abstract

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC) analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL). Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC), whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC). In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI), whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease-specific measures in adolescents with IBS. It is possible such changes will be responsive to therapeutic intervention and may be useful as potential markers of disease progression or reversal.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by chronic abdominal pain and/or discomfort, and accompanied by altered bowel patterns [1, 2]. Although more frequently studied and reported in adults, this syndrome also affects children and adolescents and is associated with the occurrence of early, adverse life events, and the development of mood and somatoform disorders into adulthood [3–5]. In Western societies alone, the reported incidence of pediatric IBS is not uncommon, with an estimated 8–23% diagnosed between 4 and 18 years (yrs.) of age [6, 7]. Furthermore, the presentation of IBS symptoms can be debilitating for a child, interfering with school and other social activities, leading to impairments in daily functioning and decreasing overall well-being and quality of life [8, 9]. Therefore, IBS represents an important clinical problem in children that needs to be addressed since identifying effective treatments for this syndrome would be life-altering for many.

By the time I get these patients, they have usually run the gamut of what the NHS has to offer and in many cases have been taken to see alternative practitioners, been given dubious allergy testing and put on exclusion diets. As well as education re diagnosis and the pain matrix as it relates to the gut brain axis we need to consider peristalsis and gas. IBS patients produce about the same amount as anyone else, but have a lower pain tolerance to distension of the gut.

Chaperoning mothers can get a little po faced about discussions around farting, I make it quite clear that everyone does it except for said mother and me. Those with feelings of painful bloating are given farting in the bath homework, on which I expect a detailed report at the next visit.

Those with an aversion to plant food can start small with tolerable amounts of lambs lettuce and rocket as a side salad, or failing that as part of a smoothie. Many young people become fascinated by gut microbiota and the microbiome in general once they have got over the yuk factor.