GIT

[Jo Bowyer]

The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/

Abstract

The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions. This interaction between microbiota and GBA appears to be bidirectional, namely through signaling from gut-microbiota to brain and from brain to gut-microbiota by means of neural, endocrine, immune, and humoral links. In this review we summarize the available evidence supporting the existence of these interactions, as well as the possible pathophysiological mechanisms involved. Most of the data have been acquired using technical strategies consisting in germ-free animal models, probiotics, antibiotics, and infection studies. In clinical practice, evidence of microbiota-GBA interactions comes from the association of dysbiosis with central nervous disorders (i.e. autism, anxiety-depressive behaviors) and functional gastrointestinal disorders. In particular, irritable bowel syndrome can be considered an example of the disruption of these complex relationships, and a better understanding of these alterations might provide new targeted therapies.

Keywords: Gut-brain axis, enteric microbiota, central nervous system, enteric nervous system, irritable bowel syndrome




Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome

https://microbiomejournal.biomedcent...168-017-0260-z

Abstract

Background
Preclinical and clinical evidence supports the concept of bidirectional brain-gut microbiome interactions. We aimed to determine if subgroups of irritable bowel syndrome (IBS) subjects can be identified based on differences in gut microbial composition, and if there are correlations between gut microbial measures and structural brain signatures in IBS.

Methods
Behavioral measures, stool samples, and structural brain images were collected from 29 adult IBS and 23 healthy control subjects (HCs). 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. The metagenomic content of samples was inferred from 16S rRNA gene sequence data using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). T1-weighted brain images were acquired on a Siemens Allegra 3T scanner, and morphological measures were computed for 165 brain regions.

Results
Using unweighted Unifrac distances with hierarchical clustering on microbial data, samples were clustered into two IBS subgroups within the IBS population (IBS1 (n = 13) and HC-like IBS (n = 16)) and HCs (n = 23) (AUROC = 0.96, sensitivity 0.95, specificity 0.67). A Random Forest classifier provided further support for the differentiation of IBS1 and HC groups. Microbes belonging to the genera Faecalibacterium, Blautia, and Bacteroides contributed to this subclassification. Clinical features distinguishing the groups included a history of early life trauma and duration of symptoms (greater in IBS1), but not self-reported bowel habits, anxiety, depression, or medication use. Gut microbial composition correlated with structural measures of brain regions including sensory- and salience-related regions, and with a history of early life trauma.

Conclusions
The results confirm previous reports of gut microbiome-based IBS subgroups and identify for the first time brain structural alterations associated with these subgroups. They provide preliminary evidence for the involvement of specific microbes and their predicted metabolites in these correlations.

Keywords

Brain-gut-microbiome axis Irritable bowel syndrome Metagenome Firmicutes Bacteroidetes

Update 06/05/2017




The Central Nervous System and the Gut Microbiome

http://www.cell.com/cell/fulltext/S0...showall%3Dtrue

Neurodevelopment is a complex process governed by both intrinsic and extrinsic signals. While historically studied by researching the brain, inputs from the periphery impact many neurological conditions. Indeed, emerging data suggest communication between the gut and the brain in anxiety, depression, cognition, and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut. These cues largely originate from the microbiome, the consortium of symbiotic bacteria that reside within all animals. Research over the past few years reveals that the gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brain barrier, myelination, neurogenesis, and microglia maturation and also modulates many aspects of animal behavior. Herein, we discuss the biological intersection of neurodevelopment and the microbiome and explore the hypothesis that gut bacteria are integral contributors to development and function of the nervous system and to the balance between mental health and disease.

Update 14/06/2017




The Gut Microbiota and Autism Spectrum Disorders

http://journal.frontiersin.org/artic...017.00120/full

Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the fecal flora and metabolic products of the gut microbiome in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune and autonomic nervous systems. In addition, an abnormal gut microbiota is associated with several diseases, such as inflammatory bowel disease (IBD), ASD and mood disorders. Here, we review the bidirectional interactions between the central nervous system and the gastrointestinal tract (brain-gut axis) and the role of the gut microbiota in the central nervous system (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective treatment for ASD.

Autism spectrum disorder (ASD) constitutes a group of brain developmental disorders, and it is defined by stereotyped behavior and deficits in communication and social interaction. ASD has a significant influence on the development of children and on society. In 2012, the estimated prevalence of ASD was 14.6 per 1,000 children aged 8 years, and the prevalence was significantly higher in boys (23.6 per 1,000) than that in girls (5.3 per 1,000) (Christensen et al., 2016). The cost of caring for a child with ASD but without an intellectual disability is £0.92 million in the United Kingdom and $1.4 million in the United States. The main costs associated with the care of children with ASD are special education services and a loss of parental productivity (Buescher et al., 2014). Therefore, the economic effects of ASD have prompted researchers to search for effective interventions. However, identifying the exact etiology and pathology of ASD is difficult, and available effective therapies are limited (Rossignol and Frye, 2012). Previous studies have focused on genetic causes, dysregulation of the immune system, inflammation, exposure to environmental toxicants, and the gut microbiota (Fakhoury, 2015). The heritability of ASD and autistic disorder was approximately 50% among Swedish children, suggesting that both genetic and environmental factors play important roles in the development of ASD (Hallmayer et al., 2011; Sandin et al., 2014). Accumulating evidence demonstrates that gastrointestinal (GI) symptoms, such as abdominal pain, gaseousness, diarrhea, constipation and flatulence, are a common comorbidity in patients with ASD (Chaidez et al., 2014). A study by Gorrindo et al. identified constipation as the most common symptom (85%) in children with ASD according to parental reports and evaluations by pediatric gastroenterologists (Gorrindo et al., 2012). The prevalence of GI symptoms ranges from 23 to 70% in children with ASD (Chaidez et al., 2014). Furthermore, the observed GI symptoms are associated with the severity of ASD (Adams et al., 2011; Gorrindo et al., 2012). Although these studies did not show a cause-effect relationship between GI symptoms and ASD, the findings suggest that the gut plays an important role in the etiology of ASD. The gut consists of millions of microbiota, and we hypothesize that the microbiota and its metabolites might be involved in the pathophysiology of ASD. Several articles have reviewed the influence of the gut microbiota on the animal central nervous system (CNS) and suggested the existence of a microbiota gut-brain axis (Bienenstock et al., 2015; Mayer et al., 2015). The microbiota-gut-brain axis is likely the method of communication between the brain and the gut microbiota. This article reviews the role of the gut microbiota in the pathology of ASD. Strategies that modulate the gut microbiota might constitute a potential therapy for patients with ASD.

Update 20/06/2017




Diet Not Connected to GI Problems in Autistic Children

http://neurosciencenews.com/gi-diet-autism-7070/

Many children with autism spectrum disorder experience significant gastrointestinal issues, but the cause of these symptoms is unknown. Professionals in the medical community have suggested a potential link between diet and gastrointestinal issues related to autism. Now, researchers from the University of Missouri School of Medicine have found that diet is not a contributing factor in these individuals. The researchers hope the findings could help lead to improved treatment options.

“Unfortunately, it’s not uncommon for those with autism to experience constipation, irritable bowel syndrome, abdominal pain and other gastrointestinal issues,” said Brad Ferguson, Ph.D., postdoctoral research fellow in the Department of Radiology at the MU School of Medicine and the MU Thompson Center for Autism and Neurodevelopmental Disorders. “We sought to find out whether nutritional intake in their individual diets was associated with gastrointestinal issues. Based on our findings, dietary intake does not appear to be the culprit for these issues, and other factors are likely at play.”


A previous study conducted by the research team identified a relationship between increased cortisol response to stress and gastrointestinal symptoms in people with autism spectrum disorder. NeuroscienceNews.com image is for illustrative purposes only.
A previous study conducted by the research team identified a relationship between increased cortisol response to stress and gastrointestinal symptoms in people with autism spectrum disorder. Cortisol is a hormone released by the body in times of stress, and one of its functions is to prevent the release of substances in the body that cause inflammation. In this study, the researchers sought to confirm or rule out dietary intake as a source of gastrointestinal problems.

The team studied 75 individuals between the ages of 5 and 18 who are part of the Autism Speaks Autism Treatment Network who were treated at the MU Thompson Center for Autism and Neurodevelopmental Disorders. The individuals’ caregivers completed a questionnaire to assess the children’s gastrointestinal symptoms, as well as a questionnaire on food intake over the past month. The individuals also underwent two stress tests to measure cortisol levels.

“We looked at the reported instances of gastrointestinal issues and compared them with 32 different nutrients found in a standard diet,” Ferguson said. “Contrary to what you may initially think, dietary composition does not appear to be a driving factor between stress response and gastrointestinal function in this sample. More research is needed to better understand the causes of these issues, but an increased reaction to stress does appear to be a contributing factor.”

Update 13/07/2017

[Jo Bowyer]

Effects of walnut consumption on colon carcinogenesis and microbial community structure

http://cancerpreventionresearch.aacr...7.CAPR-16-0026

Abstract

Walnuts are comprised of a complex array of biologically active constituents with individual cancer-protective properties. Here, we assessed the potential benefit of whole walnut consumption in a mouse tumor bioassay using azoxymethane (AOM). In study 1, a modest reduction (1.3-fold) in tumor numbers was observed in mice fed a standard diet (AIN-76A) containing 9.4% walnuts (15% of total fat). In Study 2, the effects of walnut supplementation were tested in the Total Western Diet (TWD). There was a significant reduction (2.3-fold; p<0.02) in tumor numbers in male mice fed TWD containing 7% walnuts (10.5% of total fat). Higher concentrations of walnuts lacked inhibitory effects, particularly in female mice, indicating there may be optimal levels of dietary walnut intake for cancer prevention. Since components of the Mediterranean diet have been shown to affect the gut microbiome, the effects of walnuts were therefore tested in fecal samples using 16S rRNA gene sequencing. Carcinogen treatment reduced the diversity and richness of the gut microbiome, especially in male mice, which exhibited lower variability and greater sensitivity to environmental changes. Analysis of individual operational taxonomic units (OTUs) identified specific groups of bacteria associated with carcinogen exposure, walnut consumption and/or both variables. Correlation analysis also identified specific OTU-clades that were strongly associated with the presence and number of tumors. Taken together, our results indicate that walnuts afford partial protection to the colon against a potent carcinogenic insult, and this may be due in part to walnut-induced changes to the gut microbiome.

I started eating them on a regular basis years before my obsession with gut microbiota, because they look like brains and taste nice with just about anything, sweet or savoury.





Changes in the Gut Microbial Communities Following Addition of Walnuts to the Diet


http://www.sciencedirect.com/science...110?via%3Dihub
Abstract

Walnuts are rich in omega-3 fatty acids, phytochemicals and antioxidants making them unique compared to other foods. Consuming walnuts has been associated with health benefits including a reduced risk of heart disease and cancer. Dysbiosis of the gut microbiome has been linked to several chronic diseases. One potential mechanism by which walnuts may exert their health benefit is through modifying the gut microbiome. This study identified the changes in the gut microbial communities that occur following the inclusion of walnuts in the diet. Male Fischer 344 rats (n=20) were randomly assigned to one of two diets for as long as 10 weeks: 1) walnut (W), and 2) replacement (R) in which the fat, fiber, and protein in walnuts were matched with corn oil, protein casein, and a cellulose fiber source. Intestinal samples were collected from the descending colon, the DNA isolated, and the V3-V4 hypervariable region of 16S rRNA gene deep sequenced on an Illumina MiSeq for characterization of the gut microbiota. Body weight and food intake did not differ significantly between the two diet groups. The diet groups had distinct microbial communities with animals consuming walnuts displaying significantly greater species diversity. Walnuts increased the abundance of Firmicutes and reduced the abundance of Bacteriodetes. Walnuts enriched the microbiota for probiotic-type bacteria including Lactobacillus, Ruminococcaceae, and Roseburia while significantly reducing Bacteroides and Anaerotruncus. The class Alphaproteobacteria was also reduced. Walnut consumption altered the gut microbial community suggesting a new mechanism by which walnuts may confer their beneficial health effects.

Update 29/07/2017

[Jo Bowyer]

War and peace in the human gut: Probing the microbiome

https://www.sciencedaily.com/release...0606200431.htm

According to Athena Aktipis, a researcher at Arizona State University's Biodesign Institute, microbes within the body--collectively known as the microbiota--also engage in cooperative and combative behavior with human cells in their environment. This is particularly true in the human gut, where many trillions of them exist in the digestive tract in communities of bewildering diversity.

In research appearing in the current issue of Annals of the New York Academy of Sciences, Aktipis and her colleagues Helen Wasielewski (ASU's Department of Psychology), and Joe Alcock, (at the University of New Mexico Department of Emergency Medicine), examine the role of microbes in the gut. Their study explores how dietary choices promote cooperation or might fuel conflict between gut microbes and the humans they interact with, maintaining health or encouraging the onset of disease.

The new research provides important insights into the subtle interplay of diet and human health as well as paving the way for management of the microbiome, particularly for the treatment and prevention of inflammatory and metabolic disease.

"Our gut microbes are not just passive recipients of the food that we eat -- they evolve and change in response to what we feed our bodies. And there are certain foods that lead to resource sharing between us and our microbes, while other foods can lead to conflict and resource competition between our bodies and our microbes," Aktipis says. "This cooperation and conflict framework can help us understand certain aspects of why we get sick and how we can stay healthy."

Bacterial nation

Scientists are only beginning to appreciate the significance and complexity of the bacteria comprising the microbiota, which number approximately 30 trillion, about the same number as human cells. Colonization of the body by a vast array of microbes begins at birth, when a newborn is exposed to maternal vaginal, fecal and skin flora.

Most of the human microbiota resides in the gut. At least 500 different species exist, though most fall into several well-recognized groups. Emerging research suggests the composition of these microbes exerts a profound influence on human health throughout life, including the propensity for obesity and the susceptibility to allergies. They may even affect behavior.

In the new manuscript, Aktipis and her colleagues explore the effects of particular nutrients in food on the behavior of gut bacteria. Their innovative approach applies evolutionary theory to the issue and proposes that the microbes inhabiting the human gut engage in competitive or cooperative behavior, depending in part on the particular diet they are exposed to.

Support vs strife

Cooperation and competition are hallmarks of evolutionary processes, guiding the fate of all living organisms. In the human body, conflict and cooperation between cells of differing genetic makeup can have important consequences for health and disease.

One classic example is that of cancer cells, which mutate genetically, form independent clusters and rob resources from the host for their own benefit. Cell competition can also occur between maternal cells and those of a developing fetus, another topic Aktipis has explored in earlier research.

In the current study, Aktipis and her colleagues examine cooperation and competition between the human and non-human, that is, between the cells making up human tissues and organs and the multitude of microbes (e.g. bacteria, fungi, and archaeons) co-existing in the same individual.

Cooperative behavior between humans and gut microflora occurs when bacterial cells produce energy and vitamins and help to screen out pathogens threatening the host. In return, host cells help maintain the microbial habitat, providing them with an environment conducive to their growth and proliferation--a win-win situation.

The authors propose that a cooperative alignment of needs between gut microbes and the human host should lead to positive health outcomes, while conflicts over resource utilization can often generate disease.

Helen Wasielewski, Postdoctoral Scholar in the Aktipis Lab, argues that taking a microbial perspective is useful in understanding these cooperative relationships: "Thinking about transmission, or how these microorganisms move between hosts, is really important here. If bacteria are able to move between hosts easily, they can exploit the current host and move on, whereas if they're more limited they can become dependent upon the reproductive success of the host for their own success," she says. "In extreme cases, symbionts become dependent upon their hosts to such an extent that they no longer have the capacity to live outside the host -- we see examples of this in some invertebrates."

Food fight

Internal disputes can break out when the needs of microbes and humans are at cross-purposes. Should conditions of cooperation break down, gut microbiota may contribute to chronic afflictions including inflammatory, metabolic and cardiovascular diseases or use nutrients intended for the host, causing inflammation and other negative health effects.

Sugar and fat in the diet may constitute a recipe for such internal conflict. Unlike dietary fiber, fats and simple sugars can be used not only by host cells but also by potentially harmful microbes, such as pathogenic E. coli. Instead of resource sharing, a microbial tug-of-war ensues.

When low fiber intake in the diet is combined with abundant sugar, populations of harmful microbes can expand, leading to inflammation-related illness. The ingestion of iron also carries certain health risks and can sometimes lead to internal conflict.

[Jo Bowyer]

Short Chain Fatty Acids From Fiber As Critical Signals

http://jonlieffmd.com/blog/short-cha...b9b44-90589721

Dietary fiber has been recommended for several positive health effects. However, the reasons for these effects are complex and just being discovered. As with all of life, it involves signaling among cells throughout the body including gut cells where it is ingested, microbes in the gut that metabolize it, and immune cells triggered by metabolites. These metabolites stimulate important tissue cells in gut, lungs, liver, vagina and brain. Effects include feelings of hunger, decreasing asthmatic hyper reactivity of airways, increasing lactate in the vagina and complex functions in the brain including stimulating new neurons.

Amongst the criticisms leveled at Jon Lieff here and elsewhere, are that he doesn't give a list of references and that Theory of Mind is a theme that runs through much of his writing.

I am posting this because he has done a fantastic job of simplifying immensely complex subject matter for me and possibly other coal face practitioners who do our best with a limited science base to keep abreast of reading material that informs our work.

[Jo Bowyer]

Unraveling the food web in your gut

https://www.sciencedaily.com/release...0613122345.htm

Despite recent progress, the organization and ecological properties of intestinal microbial ecosystem remain under investigated. Using a manually curated metabolic module framework for (meta-)genomic data analysis, researchers studied species-function relationships in gut microbial genomes and microbiomes. The Flemish Gut Flora Project observed that half of the bacteria in the human gut were metabolic generalists, while others were specializing and feeding on specific substrates.

Last year, the Raes team was the first to question the prevailing assumption in gut microbiome research equaling high bacterial diversity in the colon ecosystem to host health. This assumption has been put forward based on frequent observations of reduced diversity associated with disease. Based on the results published now, the Raes team links high bacteria diversity not only to slow transit, but also to depletion of carbohydrates in the large intestine and increased fermentation of proteins. The latter suggests that the link between diversity and health is not as straightforward as previously assumed.

Jeroen Raes (VIB/KU Leuven): "We found that high biodiversity enterotypes (generally considered as healthy) also have a high capacity to produce potentially unhealthy compounds as a result of protein fermentation. High colon ecosystem biodiversity is maybe not the Holy Grail in the ongoing quest to improve gut health."

The Raes team also demonstrated that bacteria fermenting proteins are slower growers. This knowledge could be used to make sure they get outcompeted by feeding our colon ecosystem carbohydrates in the form of prebiotic substrates. Prebiotics will give a selective advantage to faster growing carbohydrate fermenters that do not produce undesired metabolites.

Microbiome restoration diet improves digestion, cognition and physical and emotional wellbeing

http://journals.plos.org/plosone/art...l.pone.0179017

Abstract

Manipulating gut bacteria in the microbiome, through the use of probiotics and prebiotics, has been found to have an influence on both physical and emotional wellbeing. This study uses a dietary manipulation ‘The Gut Makeover’ designed to elicit positive changes to the gut bacteria within the microbiome. 21 healthy participants undertook ‘The Gut Makeover’ for a four week period. Weight and various aspects of health were assessed pre and post intervention using the Functional Medicine Medical Symptoms Questionnaire (MSQ). Paired sample t-tests revealed a significant reduction in self-reported weight at the end of the intervention. Adverse medical symptoms related to digestion, cognition and physical and emotional wellbeing, were also significantly reduced during the course of the dietary intervention. The intervention, designed to manipulate gut bacteria, had a significant impact on digestion, reducing IBS type symptoms in this non-clinical population. There was also a striking reduction in negative symptoms related to cognition, memory and emotional wellbeing, including symptoms of anxiety and depression. Dietary gut microbiome manipulations may have the power to exert positive physical and psychological health benefits, of a similar nature to those reported in studies using pre and probiotics. The small sample size and lack of control over confounding variables means that it will be important to replicate these findings in larger-scale controlled, prospective, clinical trials. This dietary microbiome intervention has the potential to improve physical and emotional wellbeing in the general population but also to be investigated as a treatment option for individuals with conditions as diverse as IBS, anxiety, depression and Alzheimer’s disease.

Introduction

The intestines of an average human contain trillions of gut bacteria. The diversity and strains of these bacteria vary dramatically between individuals. Research has shown that sub-optimal gut bacteria can have a profound impact on health. For example, the health of the microbiome, in terms of species and diversity of gut bacteria, has been found to be associated with digestive issues, such as nausea, bloating and diarrhoea [1] and Irritable Bowel Syndrome (IBS) [2]. Additionally, sub-optimal bacterial diversity is reported in a number of conditions that have a severe impact on health, from Crohn’s disease [3], and obesity [4] to type 2 diabetes [5].

Update 16/06/2017

[Jo Bowyer]

Retraction: Microbiome restoration diet improves digestion, cognition and physical and emotional wellbeing

After publication of this article [1], concerns were raised about the validity of the study design and conclusions reported. Following a post-publication assessment involving staff editors and members of our Editorial Board, the PLOS ONE Editors decided to retract this article due to methodological concerns that call into question the validity of the study and its conclusions which the peer review process did not adequately address.

The concerns include:

There was no control group for this study.
The participants were not blind to the treatment and were selected from a population for which placebo effects are anticipated. Furthermore, outcome data consist of self-reported measures including weight and symptoms. Self-reported weight data were not validated by the researchers, and no dietary measures were included to assess adherence to the diet. The validity and reliability of the tool used to assess participants' symptoms has not been demonstrated, and as no validated measures or scales were used to assess cognitive function or emotional well-being, the conclusions are not well-supported.
The authors did not report on potential confounding variables such as medication or dietary supplement use by participants before or during the study.
The prebiotic and probiotic components of the diet are not reported in sufficient detail to enable reproducibility. While described in general terms, quantities consumed per day and the range of such items consumed per participant are not reported.
The authors did not report a power calculation to support the sample size and demonstrate it as adequate to assess the anticipated effects.
Further concerns were raised about the statistical analysis methods and reporting: the authors did not report a statistical analysis plan and methodology clearly in their Methods section, and the application of Cronbach's alpha in the study has been questioned in light of the diverse symptoms assessed with the scale.
Reference to the intervention as a "microbiome restoration" diet is not supported, as the authors did not assess microbiome composition.
In light of the above concerns about the study design and methods used, the PLOS ONE Editors consider that the conclusions of this study are not supported by the data presented and retract this article.

KL and JH do not agree with the retraction and stand by the article’s conclusion.

[Jo Bowyer]

Retraction Watch have done an interesting analysis of this situation, which led to an editorial upheaval at PLOS

https://retractionwatch.com/2018/03/...proved-health/

[Jo Bowyer]

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis

http://journals.plos.org/plosone/art...l.pone.0157259

Abstract

Background

Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear.

Objective

We conducted this systematic review to assess the efficacy and safety of FMT in UC.

Data Sources

PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes.

Data Extraction and Synthesis

We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies.

Results

Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition.

Conclusion

FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.

[Jo Bowyer]

Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome

https://microbiomejournal.biomedcent...168-016-0171-4

Abstract

Background
Gastrointestinal disturbances are among symptoms commonly reported by individuals diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, whether ME/CFS is associated with an altered microbiome has remained uncertain. Here, we profiled gut microbial diversity by sequencing 16S ribosomal ribonucleic acid (rRNA) genes from stool as well as inflammatory markers from serum for cases (n = 48) and controls (n = 39). We also examined a set of inflammatory markers in blood: C-reactive protein (CRP), intestinal fatty acid-binding protein (I-FABP), lipopolysaccharide (LPS), LPS-binding protein (LBP), and soluble CD14 (sCD14).

Results
We observed elevated levels of some blood markers for microbial translocation in ME/CFS patients; levels of LPS, LBP, and sCD14 were elevated in ME/CFS subjects. Levels of LBP correlated with LPS and sCD14 and LPS levels correlated with sCD14. Through deep sequencing of bacterial rRNA markers, we identified differences between the gut microbiomes of healthy individuals and patients with ME/CFS. We observed that bacterial diversity was decreased in the ME/CFS specimens compared to controls, in particular, a reduction in the relative abundance and diversity of members belonging to the Firmicutes phylum. In the patient cohort, we find less diversity as well as increases in specific species often reported to be pro-inflammatory species and reduction in species frequently described as anti-inflammatory. Using a machine learning approach trained on the data obtained from 16S rRNA and inflammatory markers, individuals were classified correctly as ME/CFS with a cross-validation accuracy of 82.93 %.

Conclusions
Our results indicate dysbiosis of the gut microbiota in this disease and further suggest an increased incidence of microbial translocation, which may play a role in inflammatory symptoms in ME/CFS.

Keywords

Myalgic encephalomyelitis Chronic fatigue syndrome Inflammation Lipopolysaccharides Microbiome Microbial translocation Beta-diversity

[Jo Bowyer]

Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut

http://www.nature.com/articles/nmicrobiol201693

Abstract

Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transit time in humans, assessed using radio-opaque markers, is associated with overall gut microbial composition, diversity and metabolism. We find that a long colonic transit time associates with high microbial richness and is accompanied by a shift in colonic metabolism from carbohydrate fermentation to protein catabolism as reflected by higher urinary levels of potentially deleterious protein-derived metabolites. Additionally, shorter colonic transit time correlates with metabolites possibly reflecting increased renewal of the colonic mucosa. Together, this suggests that a high gut microbial richness does not per se imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies.

[Jo Bowyer]

Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota

http://journals.plos.org/plosone/art...l.pone.0158498

Introduction

Composed of 1011 to 1012 micro-organisms per gram of feces, and estimated to harbor more than 500 bacterial species, the human gastrointestinal microbiota is a large and diverse community of microorganisms and is in close cross-talk with its host [1–3]. Despite the vast number of bacteria and complexity found in the adult gut, the microbiota of the infant gut is initially a simple ecosystem which gradually undergoes successional changes until it reaches high diversity. For years, the infant gut was considered to be sterile, only becoming colonized after birth from the maternal microbiota, diet, and the environment [4–7]. However, recent findings suggest that microbial exposure may start already during gestation and colonization starts with the early settlers derived from the maternal microbiota and environment immediately from birth [8–11]. The development of the infant gut microbiota is profoundly influenced by host genotype, gestational age, antibiotic use, mode of delivery, diet and the context in which the infant is born (rural vs urban, presence of siblings, pets and other factors) [4, 5, 12–17].

The first colonizers of the infant gut are facultative anaerobic bacteria, such as Staphylococcus, Streptococcus, Enterococcus and Enterobacter spp, which by reducing the oxygen levels that initially exist, pave the way for anaerobes such as Bifidobacterium, Bacteroides and Clostridium spp. to start colonizing the gut. It is known that the type of bacteria that initially colonize the infant gut and the time frame in which this occurs, is highly dependent on the mode of delivery. Previous studies have demonstrated that strains originating from the maternal gut and vagina are transferred to the infant’s gut in case of a vaginal delivery (VD) [18–20], while infants born by cesarean section (CS) are suggested to be initially colonized by bacteria from the environment such as from maternal skin, hospital staff or other neonates [21].

The first weeks of life is a period in which the intestinal microbiota is very dynamic, with nutrition governing the developing ecosystem [15]. Breastfed infants typically have a bifidobacteria-dominated microbiota whereas formula-fed infants have a more diverse microbiota. After the introduction of solid foods, bacterial succession continues gradually diversifying with adult-like species such as Bacteroides spp. and Clostridium cluster IV and XIV. The exact age at which a stable adult-like composition is established is still unclear but it is thought to be around 3 years of age [22, 23]. However, this process continues past 3 years of age, and events occurring later in life, such as hormonal changes during puberty or changes in eating habits may also influence the microbiota composition [24, 25].

To what extend early colonization is influencing the microbiota composition in later life needs to be further elucidated. However, increasing evidence suggests that the initial colonization does influence gut maturation, immune, brain and metabolic development. Early-life events (ie., mode of delivery, type of feeding, antibiotic use) that are known to influence this process, may thus drive predisposition to diseases later in life [13, 26–31]. It is therefore critical to understand the early colonization process in great detail, including the confounding factors in early life that can be of long term importance.

This study aims to describe the dynamics of early colonization during the first six months of life and identify factors that can drive changes in the composition of the gut microbiota in early life.

Bacterial Clues in Baby’s Dirty Diapers Helps Predict Cognitive Development

http://neurosciencenews.com/bacteria...elopment-7103/

Using fecal samples taken from dozens of one-year-olds and cognitive assessments of the same children a year later, researchers in the lab of Rebecca Knickmeyer, PhD, associate professor of psychiatry, found an association between certain kinds of microbial communities and higher levels of cognitive development later on. The results were published in Biological Psychiatry.

“The big story here is that we’ve got one group of kids with a particular community of bacteria that’s performing better on these cognitive tests,” said Knickmeyer. “This is the first time an association between microbial communities and cognitive development has been demonstrated in humans.”

The gut is home to trillions of microbes that can have an enormous impact on the health of individuals, affecting everything from our ability to metabolize the nutrients in our food to our risk for developing gastrointestinal disorders like colitis. This community of microbes, also known as the microbiome, can be characterized in several ways, but one of the most common is to estimate the relative abundance of different kinds of bacteria using the combined genetic material of all microorganisms in a particular environment, in this case the gut.

Knickmeyer and her colleagues sought to determine whether there might be a relationship between the gut microbiome and brain development

Update 18/07/2017

[Jo Bowyer]

The Rapunzel syndrome. Report of a case.

Abstract

Trichobezoar is a rare pathology in which swallowed hairs accumulate in the stomach. An unusual form of bezoar extending from the stomach to the small intestine or beyond has been described as Rapunzel syndrome. Trichobezoars typically cause abdominal pain and nausea, but can also present as an asymptomatic abdominal mass, progressing to abdominal obstruction and perforation. Trichobezoar with Rapunzel syndrome is an uncommon diagnosis. It is predominantly found in emotionally disturbed or mentally retarded young people. The diagnosis may be suspected in young females with abdominal pain, epigastric mass and malnutrition, who have a history of trichophagia. The Authors present a case of successful laparotomy removal of a giant gastro-duodenal trichobezoar in a 9-year-old girl with a history of trichotillophagia. Physical examination revealed diffuse abdominal pain and an epigastric mass. Psychodynamic aspects, clinical manifestations, diagnosis and therapautic strategies are discussed.

It is described in 19th century medical textbooks as a disorder affecting young girls in the schoolroom who would chew on their plaits while writing on their slates. I have yet to see a case despite many years dealing with medically unexplained abdominal pain in children. Very occasionally a case will be reported in the press, usually before the bezoar gets to the stage where it invades the duodenum.

I do talk about them to young girls who chew their hair and explain that unlike the Harry Potter stories, having a bezoar in your stomach is not a good idea.

[Jo Bowyer]

These days fecal transplantation is no joke

https://www.sciencedaily.com/release...0712142633.htm

"This research is just getting started. It is driven by the new paradigm of the microbiome which recognizes that every plant and animal species harbors a collection of microbes that have significant and previously unrecognized effects on their host health, evolution and behavior," said Seth Bordenstein, associate professor of biological sciences and pathology, microbiology, and immunology at Vanderbilt University.

In an article titled "Fecal Transplants: What is Being Transferred" published July 12 in the journal PLOS Biology, Bordenstein reviews the growing scientific literature on the subject.

"There is no doubt that poo can save lives," said Bordenstein. Take the case of the use of fecal transplants to treat Clostridium difficile infections. According to the literature, it has a 95 percent cure rate. "Right now fecal transplants are used as the treatment of last resort, but their effectiveness raises an important question: When will doctors start prescribing them, or some derivative, first?" Bordenstein asked.

[Jo Bowyer]

Fecal Transplants: What Is Being Transferred?

http://journals.plos.org/plosbiology...l.pbio.1002503

[Jo Bowyer]

Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria

http://journals.plos.org/plosone/art...l.pone.0159030

Abstract

The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being.

[Jo Bowyer]

Biologists home in on paleo gut for clues to our evolutionary history

https://www.sciencedaily.com/release...0721151457.htm

A new study of the gut microbiomes of humans, chimps, bonobos and gorillas shows that at least two major groups of bacteria have cospeciated with these hosts, with a lineage going back at least 15 million years to our last common ancestor. Researchers hope to reconstruct the ancestral 'paleo gut' that went with our paleo diet, and use the gut bacteria to track human migration.

[Jo Bowyer]

Host Gut Motility Promotes Competitive Exclusion within a Model Intestinal Microbiota

http://journals.plos.org/plosbiology...l.pbio.1002517

Abstract

The gut microbiota is a complex consortium of microorganisms with the ability to influence important aspects of host health and development. Harnessing this “microbial organ” for biomedical applications requires clarifying the degree to which host and bacterial factors act alone or in combination to govern the stability of specific lineages. To address this issue, we combined bacteriological manipulation and light sheet fluorescence microscopy to monitor the dynamics of a defined two-species microbiota within a vertebrate gut. We observed that the interplay between each population and the gut environment produces distinct spatiotemporal patterns. As a consequence, one species dominates while the other experiences sudden drops in abundance that are well fit by a stochastic mathematical model. Modeling revealed that direct bacterial competition could only partially explain the observed phenomena, suggesting that a host factor is also important in shaping the community. We hypothesized the host determinant to be gut motility, and tested this mechanism by measuring colonization in hosts with enteric nervous system dysfunction due to a mutation in the ret locus, which in humans is associated with the intestinal motility disorder known as Hirschsprung disease. In mutant hosts we found reduced gut motility and, confirming our hypothesis, robust coexistence of both bacterial species. This study provides evidence that host-mediated spatial structuring and stochastic perturbation of communities can drive bacterial population dynamics within the gut, and it reveals a new facet of the intestinal host–microbe interface by demonstrating the capacity of the enteric nervous system to influence the microbiota. Ultimately, these findings suggest that therapeutic strategies targeting the intestinal ecosystem should consider the dynamic physical nature of the gut environment.