The human gut is inhabited by trillions of microorganisms composing a dynamic ecosystem implicated in health and disease. The composition of the gut microbiota is unique to each individual and tends to remain relatively stable throughout life, yet daily transient fluctuations are observed. Diet is a key modifiable factor influencing the composition of the gut microbiota, indicating the potential for therapeutic dietary strategies to manipulate microbial diversity, composition, and stability. While diet can induce a shift in the gut microbiota, these changes appear to be temporary. Whether prolonged dietary changes can induce permanent alterations in the gut microbiota is unknown, mainly due to a lack of long-term human dietary interventions, or long-term follow-ups of short-term dietary interventions. It is possible that habitual diets have a greater influence on the gut microbiota than acute dietary strategies. This review presents the current knowledge around the response of the gut microbiota to short-term and long-term dietary interventions and identifies major factors that contribute to microbiota response to diet. Overall, further research on long-term diets that include health and microbiome measures is required before clinical recommendations can be made for dietary modulation of the gut microbiota for health.

Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration

Low concordance between studies that examine the role of microbiota in human diseases is a pervasive challenge that limits the capacity to identify causal relationships between host-associated microorganisms and pathology. The risk of obtaining false positives is exacerbated by wide interindividual heterogeneity in microbiota composition1, probably due to population-wide differences in human lifestyle and physiological variables2 that exert differential effects on the microbiota. Here we infer the greatest, generalized sources of heterogeneity in human gut microbiota profiles and also identify human lifestyle and physiological characteristics that, if not evenly matched between cases and controls, confound microbiota analyses to produce spurious microbial associations with human diseases. We identify alcohol consumption frequency and bowel movement quality as unexpectedly strong sources of gut microbiota variance that differ in distribution between healthy participants and participants with a disease and that can confound study designs. We demonstrate that for numerous prevalent, high-burden human diseases, matching cases and controls for confounding variables reduces observed differences in the microbiota and the incidence of spurious associations. On this basis, we present a list of host variables that we recommend should be captured in human microbiota studies for the purpose of matching comparison groups, which we anticipate will increase robustness and reproducibility in resolving the members of the gut microbiota that are truly associated with human disease.

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Host variables confound gut microbiota studies of human disease.

Objective The microbiome directly affects the balance of pro-inflammatory and anti-inflammatory responses in the gut. As microbes thrive on dietary substrates, the question arises whether we can nourish an anti-inflammatory gut ecosystem. We aim to unravel interactions between diet, gut microbiota and their functional ability to induce intestinal inflammation. Design We investigated the relation between 173 dietary factors and the microbiome of 1425 individuals spanning four cohorts: Crohn’s disease, ulcerative colitis, irritable bowel syndrome and the general population. Shotgun metagenomic sequencing was performed to profile gut microbial composition and function. Dietary intake was assessed through food frequency questionnaires. We performed unsupervised clustering to identify dietary patterns and microbial clusters. Associations between diet and microbial features were explored per cohort, followed by a meta-analysis and heterogeneity estimation. Results We identified 38 associations between dietary patterns and microbial clusters. Moreover, 61 individual foods and nutrients were associated with 61 species and 249 metabolic pathways in the meta-analysis across healthy individuals and patients with IBS, Crohn’s disease and UC (false discovery rate Conclusion We identified dietary patterns that consistently correlate with groups of bacteria with shared functional roles in both, health and disease. Moreover, specific foods and nutrients were associated with species known to infer mucosal protection and anti-inflammatory effects. We propose microbial mechanisms through which the diet affects inflammatory responses in the gut as a rationale for future intervention studies.

https://gut.bmj.com/content/gutjnl/70/7/1287.full.pdf

Long-term dietary patterns are associated with pro-inflammatory and anti-inflammatory features of the gut microbiome

Irritable bowel syndrome (IBS) remains one of the most common gastrointestinal disorders seen by clinicians in both primary and secondary care. Since publication of the last British Society of Gastroenterology (BSG) guideline in 2007, substantial advances have been made in understanding its complex pathophysiology, resulting in its re-classification as a disorder of gut-brain interaction, rather than a functional gastrointestinal disorder. Moreover, there has been a considerable amount of new evidence published concerning the diagnosis, investigation and management of IBS. The primary aim of this guideline, commissioned by the BSG, is to review and summarise the current evidence to inform and guide clinical practice, by providing a practical framework for evidence-based management of patients. One of the strengths of this guideline is that the recommendations for treatment are based on evidence derived from a comprehensive search of the medical literature, which was used to inform an update of a series of trial-based and network meta-analyses assessing the efficacy of dietary, pharmacological and psychological therapies in treating IBS. Specific recommendations have been made according to the Grading of Recommendations Assessment, Development and Evaluation system, summarising both the strength of the recommendations and the overall quality of evidence. Finally, this guideline identifies novel treatments that are in development, as well as highlighting areas of unmet need for future research.

https://gut.bmj.com/content/gutjnl/70/7/1214.full.pdf

British Society of Gastroenterology guidelines on the management of irritable bowel syndrome

Atherosclerosis, the main contributor to coronary heart disease, is characterised by an accumulation of lipids such as cholesterol in the arterial wall. Reverse cholesterol transport (RCT) reduces cholesterol via its conversion into bile acids (BAs). During RCT in non-hepatic peripheral tissues, cholesterol is transferred to high-density lipoprotein (HDL) particles and returned to the liver for conversion into BAs predominantly via the rate-limiting enzyme, cholesterol 7 α-hydroxylase (CYP7A1). Numerous reports have described that polyphenol induced increases in BA excretion and corresponding reductions in total and LDL cholesterol in animal and in-vitro studies, but the process whereby this occurs has not been extensively reviewed. There are three main mechanisms by which BA excretion can be augmented: (1) increased expression of CYP7A1; (2) reduced expression of intestinal BA transporters; and (3) changes in the gut microbiota. Here we summarise the BA metabolic pathways focusing on CYP7A1, how its gene is regulated via transcription factors, diurnal rhythms, and microRNAs. Importantly, we will address the following questions: (1) Can polyphenols enhance BA secretion by modulating the CYP7A1 biosynthetic pathway? (2) Can polyphenols alter the BA pool via changes in the gut microbiota? (3) Which polyphenols are the most promising candidates for future research? We conclude that while in rodents some polyphenols induce CYP7A1 expression predominantly by the LXRα pathway, in human cells, this may occur through FXR, NF-KB, and ERK signalling. Additionally, gut microbiota is important for the de-conjugation and excretion of BAs. Puerarin, resveratrol, and quercetin are promising candidates for further research in this area.

https://www.mdpi.com/2072-6643/11/11/2588/pdf

Polyphenol Effects on Cholesterol Metabolism via Bile Acid Biosynthesis, CYP7A1: A Review.

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal1, leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders.

/pdf/local-immune-response-to-food-antigens-drives-meal-induced-jxweadlqgb.pdf

Local immune response to food antigens drives meal-induced abdominal pain

Red Wine Consumption Associated With Increased Gut Microbiota α-Diversity in 3 Independent Cohorts

As wheat (Triticum aestivum) is an important staple food across the world, preservation of stable yields and increased productivity are major objectives in breeding programs. Drought is a global concern because its adverse impact is expected to be amplified in the future due to the current climate change. Here, we analyzed the effects of edaphic, environmental, and host factors on the wheat root microbiomes collected in soils from six regions in Belgium. Amplicon sequencing analysis of unplanted soil and wheat root endosphere samples indicated that the microbial community variations can be significantly explained by soil pH, microbial biomass, wheat genotype, and soil sodium and iron levels. Under drought stress, the biodiversity in the soil decreased significantly, but increased in the root endosphere community, where specific soil parameters seemingly determine the enrichment of bacterial groups. Indeed, we identified a cluster of drought-enriched bacteria that significantly correlated with soil compositions. Interestingly, integration of a functional analysis further revealed a strong correlation between the same cluster of bacteria and β-glucosidase and osmoprotectant proteins, two functions known to be involved in coping with drought stress. By means of this in silico analysis, we identified amplicon sequence variants (ASVs) that could potentially protect the plant from drought stress and validated them in planta. Yet, ASVs based on 16S rRNA sequencing data did not completely distinguish individual isolates because of their intrinsic short sequences. Our findings support the efforts to maintain stable crop yields under drought conditions through implementation of root microbiome analyses.

Jiyeon Si

Papers

Local immune response to food antigens drives meal-induced abdominal pain

Red Wine Consumption Associated With Increased Gut Microbiota α-Diversity in 3 Independent Cohorts

Interactions between soil compositions and the wheat root microbiome under drought stress: From an in silico to in planta perspective.