Search

Intestinal inflammation shifts microbiota composition and metabolism. How the host monitors and responds to such changes remains unclear. Here, we describe a protective mechanism by which mucosal-associated invariant T (MAIT) cells detect microbiota metabolites produced upon intestinal inflammation and promote tissue repair. At steady state, MAIT ligands derived from the riboflavin biosynthesis pathway were produced by aerotolerant bacteria residing in the colonic mucosa. Experimental colitis triggered luminal expansion of riboflavin-producing bacteria, leading to increased production of MAIT ligands. Modulation of intestinal oxygen levels suggested a role for oxygen in inducing MAIT ligand production. MAIT ligands produced in the colon rapidly crossed the intestinal barrier and activated MAIT cells, which expressed tissue-repair genes and produced barrier-promoting mediators during colitis. Mice lacking MAIT cells were more susceptible to colitis and colitis-driven colorectal cancer. Thus, MAIT cells are sensitive to a bacterial metabolic pathway indicative of intestinal inflammation. Editor's summary: Changes in the gut microbiota have been linked to intestinal inflammation, but how these shifts are sensed by the host is not completely understood. Using an experimental colitis model in mice, El Morr et al. defined a role for mucosal-associated invariant T (MAIT) cells in sensing increases in MAIT ligands associated with the expansion of riboflavin-producing aerotolerant bacteria in the gut lumen. MAIT cells are then activated upon sensing these ligands and produce anti-inflammatory molecules and mediators of tissue repair. In the absence of MAIT cells, mice are more susceptible to colitis pathology and progression to colorectal cancer. —Christiana Fogg [ABSTRACT FROM AUTHOR]

Host–microbial co-metabolism products are being increasingly recognised to play important roles in physiological processes. However, studies undertaking a comprehensive approach to consider host–microbial metabolic relationships remain scarce. Metabolomic analysis yielding detailed information regarding metabolites found in a given biological compartment holds promise for such an approach. This work aimed to explore the associations between host plasma metabolomic signatures and gut microbiota composition in healthy adults of the Milieu Intérieur study. For 846 subjects, gut microbiota composition was profiled through sequencing of the 16S rRNA gene in stools. Metabolomic signatures were generated through proton NMR analysis of plasma. The associations between metabolomic variables and α- and β-diversity indexes and relative taxa abundances were tested using multi-adjusted partial Spearman correlations, permutational ANOVA and multivariate associations with linear models, respectively. A multiple testing correction was applied (Benjamini–Hochberg, 10 % false discovery rate). Microbial richness was negatively associated with lipid-related signals and positively associated with amino acids, choline, creatinine, glucose and citrate (−0·133 ≤ Spearman's ρ ≤ 0·126). Specific associations between metabolomic signals and abundances of taxa were detected (twenty-five at the genus level and nineteen at the species level): notably, numerous associations were observed for creatinine (positively associated with eleven species and negatively associated with Faecalibacterium prausnitzii). This large-scale population-based study highlights metabolites associated with gut microbial features and provides new insights into the understanding of complex host–gut microbiota metabolic relationships. In particular, our results support the implication of a 'gut–kidney axis'. More studies providing a detailed exploration of these complex interactions and their implications for host health are needed. [ABSTRACT FROM AUTHOR]

Interactions between the prokaryotic microbiome and eukaryotic parasites in the vertebrate gut may affect overall host health and disease. While intertropical areas exhibit a high rate of parasites carriers, such interactions are understudied in these populations. Our objectives were to (1) describe the gut microbiome of individuals living in Madagascar, (2) identify potential associations between bacterial taxa and parasites colonizing the digestive tract and (3) highlight main determinants of the gut microbiota composition in this developing country. Metadata (socioeconomic, diet, clinical) and fecal samples were collected from 219 volunteers from North-West Madagascar (Mahajanga). Fecal microbiome was assessed through 16S rRNA gene sequencing and metabolomics, and related to dietary habits and parasites carriage. We highlight important Malagasy gut microbiome peculiarities. Out of three detected enterotypes, only one is similar to that observed in Westernized countries (Ruminococcus-driven). Functions associated with the two others (Clostridium sensu stricto-driven and Escherichia/Shigella-driven) are mostly directed toward amino acids biosynthesis and degradation, respectively. Diet and protozoan carriage were the main drivers of microbiota composition. High protozoan carriage was associated with higher diversity, richness and microbial functionalities. The gut microbiome of Malagasy strongly differs from that of Westernized countries. Asymptomatic protozoan carriage and dietary habits are the external factors with the deepest impact on gut microbiome. Further studies are needed to understand whether gut microbial richness constitute a predilection niche for protozoans colonization, due to their gazing features, or whether the parasites themselves induce a higher bacterial richness. [ABSTRACT FROM AUTHOR]

Background Diet is widely recognized as one of the main modifiable drivers of gut microbiota variability, and its influence on microbiota composition is an active area of investigation. Objective The present work aimed to explore the associations between usual diet and gut microbiota composition in a large sample of healthy French adults. Methods Gut microbiota composition was established through sequencing of the 16S rRNA gene in stool samples from 862 healthy French adults of the Milieu Intérieur study. Usual dietary consumptions were determined through the administration of a food-frequency questionnaire. The associations between dietary variables and α- and β-diversity indexes and relative taxa abundances were tested using Spearman correlations, permutational ANOVAs, and multivariate analyses with linear models, respectively. Results Foods generally considered as healthy (raw fruits, fish) were positively associated with α-diversity, whereas food items for which a limited consumption is generally recommended (fried products, sodas or sugary drinks, fatty sweet products, processed meats, ready-cooked meals, and desserts) were negatively associated with α-diversity. Fruits, fried products, ready-cooked meals, and cheese contributed to shifts within microbiota composition (β-diversity). Our results also highlighted a number of associations between various food group intakes and abundances of specific phyla, genera, and species. For instance, the consumption of cheese was negatively associated with Akkermansia muciniphila abundance. Conclusions This large-scale population-based study supports that the usual consumption of certain food items is associated with several gut microbial features, and extends the mechanistic arguments linking Western diet to an altered microbiota composition. These results provide new insights into the understanding of complex diet–gut microbiota relations, and their implications for host health deserve further investigation because altered microbiota diversity was consistently linked to increased risk of several health outcomes. This trial was registered at clinicaltrials.gov as NCT01699893. [ABSTRACT FROM AUTHOR]

The microorganisms inhabiting the human gut are abundant (1014 cells) and diverse (approximately 500 species per individual). It is now acknowledged that the microbiota has coevolved with its host to achieve a symbiotic relationship, leading to physiological homeostasis. The gut microbiota ensures vital functions, such as food digestibility, maturation of the host immune system, and protection against pathogens. Over the last few decades, the gut microbiota has also been associated with numerous diseases, such as inflammatory bowel disease, irritable bowel syndrome, obesity, and metabolic diseases. In most of these pathologies, a microbial dysbiosis has been found, indicating shifts in the taxonomic composition of the gut microbiota and changes in its functionality. Our understanding of the influence of the gut microbiota on human health is still growing. Working with microorganisms residing in the gut is challenging since most of them are anaerobic and a vast majority (approximately 75%) are uncultivable to date. Recently, a wide range of new approaches (meta-omics) has been developed to bypass the uncultivability and reveal the intricate mechanisms that sustain gut microbial homeostasis. After a brief description of these approaches (metagenomics, metatranscriptomics, metaproteomics, and metabolomics), this review will discuss the importance of considering the gut microbiome as a structured ecosystem and the use of meta-omics to decipher dysfunctions of the gut microbiome in diseases. [ABSTRACT FROM AUTHOR]

The intestinal microbiota is known to regulate host energy homeostasis and can be influenced by high-calorie diets. However, changes affecting the ecosystem at the functional level are still not well characterized. We measured shifts in cecal bacterial communities in mice fed a carbohydrate or high-fat (HF) diet for 12 weeks at the level of the following: (i) diversity and taxa distribution by high-throughput 16S ribosomal RNA gene sequencing; (ii) bulk and single-cell chemical composition by Fourier-transform infrared- (FT-IR) and Raman micro-spectroscopy and (iii) metaproteome and metabolome via high-resolution mass spectrometry. High-fat diet caused shifts in the diversity of dominant gut bacteria and altered the proportion of Ruminococcaceae (decrease) and Rikenellaceae (increase). FT-IR spectroscopy revealed that the impact of the diet on cecal chemical fingerprints is greater than the impact of microbiota composition. Diet-driven changes in biochemical fingerprints of members of the Bacteroidales and Lachnospiraceae were also observed at the level of single cells, indicating that there were distinct differences in cellular composition of dominant phylotypes under different diets. Metaproteome and metabolome analyses based on the occurrence of 1760 bacterial proteins and 86 annotated metabolites revealed distinct HF diet-specific profiles. Alteration of hormonal and anti-microbial networks, bile acid and bilirubin metabolism and shifts towards amino acid and simple sugars metabolism were observed. We conclude that a HF diet markedly affects the gut bacterial ecosystem at the functional level. [ABSTRACT FROM AUTHOR]

Advances in sequencing technology and the development of metagenomic and bioinformatics methods have opened up new ways to investigate the 1014 microorganisms inhabiting the human gut. The gene composition of human gut microbiome in a large and deeply sequenced cohort highlighted an overall nonredundant genome size 150 times larger than the human genome. The in silico predictions based on metagenomic sequencing are now actively followed, compared and challenged using additional 'omics' technologies. Interactions between the microbiota and its host are of key interest in several pathologies and applying metaomics to describe the human gut microbiome will give a better understanding of this crucial crosstalk at mucosal interfaces. Adding to the growing appreciation of the importance of the microbiome is the discovery that numerous phages, that is, viruses of prokaryotes infecting bacteria (bacteriophages) or archaea with a high host specificity, inhabit the human gut and impact microbial activity. In addition, gene exchanges within the gut microbiota have proved to be more frequent than anticipated. Taken together, these innovative exploratory technologies are expected to unravel new information networks critical for gut homeostasis and human health. Among the challenges faced, the in vivo validation of these networks, together with their integration into the prediction and prognosis of disease, may require further working hypothesis and collaborative efforts. [ABSTRACT FROM AUTHOR]

Simple Summary: Antibiotics perturb the gastrointestinal microbiota by killing bacteria beneficial for animal health and favoring the emergence of potential pathogens. Furthermore, antibiotics favor the emergence of resistant bacteria. Current knowledge on animals' intestinal microbiota and effects of antibiotics is blurred by the various posology, administration routes, and implemented methodologies for its analysis. We summarized 71 studies analyzing the administration of antibiotics by different routes, conducted on the main food-producing and companion animals, highlighting differences in the methodology applied for the intestinal microbiota and antibiotic resistance analysis. Overall, therapeutic dosage decreased bacterial species diversity and richness in the microbiota and selected antibiotic resistance genes. For non-therapeutic dosage, information on the selection of antibiotic resistance was scarce and the effect on the intestinal microbiota scattered. Understanding the gut microbiota composition and function in animals could open up strategies for its modulation to improve animal health and performance, and to minimize the negative impact of antibiotics. Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential pathogens. Furthermore, the intestine is a reactor of antibiotic resistance emergence, and the presence of antibiotics exacerbates the selection of resistant bacteria that can disseminate in the environment and propagate to further hosts. We reviewed studies analyzing the effect of antibiotics on the intestinal microbiota and antibiotic resistance conducted on animals, focusing on the main food-producing and companion animals. Irrespective of antibiotic classes and animal hosts, therapeutic dosage decreased species diversity and richness favoring the bloom of potential enteropathogens and the selection of antibiotic resistance. These negative effects of antibiotic therapies seem ineluctable but often were mitigated when an antibiotic was administered by parenteral route. Sub-therapeutic dosages caused the augmentation of taxa involved in sugar metabolism, suggesting a link with weight gain. This result should not be interpreted positively, considering that parallel information on antibiotic resistance selection was rarely reported and selection of antibiotic resistance is known to occur also at low antibiotic concentration. However, studies on the effect of antibiotics as growth promoters put the basis for understanding the gut microbiota composition and function in this situation. This knowledge could inspire alternative strategies to antibiotics, such as probiotics, for improving animal performance. This review encompasses the analysis of the main animal hosts and all antibiotic classes, and highlights the future challenges and gaps of knowledge that should be filled. Further studies are necessary for elucidating pharmacodynamics in animals in order to improve therapy duration, antibiotic dosages, and administration routes for mitigating negative effects of antibiotic therapies. Furthermore, this review highlights that studies on aminoglycosides are almost inexistent, and they should be increased, considering that aminoglycosides are the first most commonly used antibiotic family in companion animals. Harmonization of experimental procedures is necessary in this research field. In fact, current studies are based on different experimental set-up varying for antibiotic dosage, regimen, administration, and downstream microbiota analysis. In the future, shotgun metagenomics coupled with long-reads sequencing should become a standard experimental approach enabling to gather comprehensive knowledge on GIM in terms of composition and taxonomic functions, and of ARGs. Decorticating GIM in animals will unveil revolutionary strategies for medication and improvement of animals' health status, with positive consequences on global health. [ABSTRACT FROM AUTHOR]

Alterations of gut microbiota may play a role in Anorexia Nervosa (AN) through perturbations of the gut-brain axis. Some studies found differences in the gut microbiota of patients with AN compared to healthy controls, but results are heterogeneous. The aim of this work was to systematically review the existing studies comparing gut microbial composition in AN and healthy controls, and to perform a quantitative synthesis of the pooled clinical and microbiological data, when available. A comprehensive literature search was performed to identify human studies investigating relationships between AN and gut microbiota. Microbiome datasets from studies were pooled and analysed focusing on alpha and beta-diversity and the relative abundance of microbial species in patients' gut microbiota compared to healthy controls. Nine studies were eligible for the systematic review, of which 4 were included in the quantitative synthesis. Preserved alpha-diversity and decreased beta-diversity in AN emerged from the qualitative synthesis, while a slight increase of alpha-diversity (d < 0.4) and comparable beta-diversity were reported by the quantitative synthesis. Out of the 46 common species compared, three had a large combined effect size (d ≥ 0.9) to differentiate patients from controls, namely Alistipes , Parabacterioides and Roseburia. The latter was also correlated with BMI (ρ = 0.29). The decrease of butyrate-producing species and the increase of mucine-degrading species may represent hallmarks of the gut microbiota alterations in AN, and therefore potentially interesting therapeutic targets. The heterogeneity of clinical and methodological characteristics hampers the generalizability of the results. Standardized research methods could improve comparability among studies to better identify the alterations of gut microbiota in AN. • Gut dysbiosis may play a role in Anorexia Nervosa by altering the Gut-Brain Axis. • Nine studies explored the gut microbiota in Anorexia Nervosa and healthy controls. • An increase of intestinal mucine-degrading bacteria was found in gut microbiota of patients with Anorexia Nervosa. • A decrease of butyrate producing species was found in gut microbiota of patients with Anorexia Nervosa. • Great heterogeneity of methodologies limits comparability among studies. [ABSTRACT FROM AUTHOR]

The gut microbiota is increasingly implicated in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC) although the identity of the bacteria that underpin these diseases has remained elusive. The pathobiont Bacteroides vulgatus has been associated with both diseases although relatively little is known about how its growth and functional activity might drive the host inflammatory response. We identified an ATP Binding Cassette (ABC) export system and lipoprotein in B. vulgatus ATCC 8482 and B. vulgatus PC510 that displayed significant sequence similarity to an NF-κB immunomodulatory regulon previously identified on a CD-derived metagenomic fosmid clone. Interestingly, the ABC export system was specifically enriched in CD subjects suggesting that it may be important for colonization and persistence in the CD gut environment. Both B. vulgatus ATCC 8482 and PC510 activated NF-κB in a strain and growth phase specific manner in a HT-29/kb-seap-25 enterocyte like cell line. B. vulgatus ATCC 8482 also activated NF-κB in a Caco-2-NF-κ Bluc enterocyte like and an LS174T-NF-κB luc goblet cell like cell lines, and induced NF-κB-p65 subunit nuclear translocation and IL-6, IL-8, CXCL-10 and MCP-1 gene expression. Despite this, NF-κB activation was not coincident with maximal expression of the ABC exporter or lipoprotein in B. vulgatus PC510 suggesting that the regulon may be necessary but not sufficient for the immunomodulatory effects. [ABSTRACT FROM AUTHOR]