Summary
The human gut microbiota ferments dietary non‐digestible carbohydrates into short‐chain fatty acids (SCFA). These microbial products are utilized by the host and propionate and butyrate in ...particular exert a range of health‐promoting functions. Here an overview of the metabolic pathways utilized by gut microbes to produce these two SCFA from dietary carbohydrates and from amino acids resulting from protein breakdown is provided. This overview emphasizes the important role played by cross‐feeding of intermediary metabolites (in particular lactate, succinate and 1,2‐propanediol) between different gut bacteria. The ecophysiology, including growth requirements and responses to environmental factors, of major propionate and butyrate producing bacteria are discussed in relation to dietary modulation of these metabolites. A detailed understanding of SCFA metabolism by the gut microbiota is necessary to underpin effective strategies to optimize SCFA supply to the host.
Many factors shape the ability of different microbes to coexist in microbial communities. In the human gut, dietary and host-derived nutrients largely drive microbial community structure. How gut ...microbes with very similar nutrient profiles are able to coexist over time within the same host is not fully understood. Tuncil et al. (mBio 8:e01068-17, 2017, https://doi.org/10.1128/mBio.01068-17) explored glycan prioritization in two closely related human gut bacteria,
and
, on complex glycan mixtures that both organisms can degrade. Determining depletion of the individual glycans over time in pure cultures and cocultures revealed that the bacteria seem to have hardwired differences in their preferences for different glycans which likely contribute to their stable coexistence. The researchers also established that gene expression changes of the corresponding polysaccharide utilization loci did not always mirror glycan depletion, which highlights that additional regulatory mechanisms must be present.
Accumulating evidence suggests that the human intestinal microbiota contributes to the aetiology of colorectal cancer (CRC), not only via the pro-carcinogenic activities of specific pathogens but ...also via the influence of the wider microbial community, particularly its metabolome. Recent data have shown that the short-chain fatty acids acetate, propionate and butyrate function in the suppression of inflammation and cancer, whereas other microbial metabolites, such as secondary bile acids, promote carcinogenesis. In this Review, we discuss the relationship between diet, microbial metabolism and CRC and argue that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Butyrate-producing bacteria play a key role in colonic health in humans. This review provides an overview of the current knowledge of the diversity, metabolism and microbial ecology of this ...functionally important group of bacteria. Human colonic butyrate producers are Gram-positive firmicutes, but are phylogenetically diverse, with the two most abundant groups related to Eubacterium rectale/Roseburia spp. and to Faecalibacterium prausnitzii. Five different arrangements have been identified for the genes of the central pathway involved in butyrate synthesis, while in most cases butyryl-CoA : acetate CoA-transferase, rather than butyrate kinase, appears to perform the final step in butyrate synthesis. Mechanisms have been proposed recently in non-gut Clostridium spp. whereby butyrate synthesis can result in energy generation via both substrate-level phosphorylation and proton gradients. Here we suggest that these mechanisms also apply to the majority of butyrate producers from the human colon. The roles of these bacteria in the gut community and their influence on health are now being uncovered, taking advantage of the availability of cultured isolates and molecular methodologies. Populations of F. prausnitzii are reported to be decreased in Crohn's disease, for example, while populations of Roseburia relatives appear to be particularly sensitive to the diet composition in human volunteer studies.
The release of energy from particulate substrates such as dietary fiber and resistant starch (RS) in the human colon may depend on the presence of specialist primary degraders (or 'keystone species') ...within the microbial community. We have explored the roles of four dominant amylolytic bacteria found in the human colon in the degradation and utilization of resistant starches. Eubacterium rectale and Bacteroides thetaiotaomicron showed limited ability to utilize RS2- and RS3-resistant starches by comparison with Bifidobacterium adolescentis and Ruminococcus bromii. In co-culture, however, R. bromii proved unique in stimulating RS2 and RS3 utilization by the other three bacterial species, even in a medium that does not permit growth of R. bromii itself. Having previously demonstrated low RS3 fermentation in vivo in two individuals with undetectable populations of R. bromii-related bacteria, we show here that supplementation of mixed fecal bacteria from one of these volunteers with R. bromii, but not with the other three species, greatly enhanced the extent of RS3 fermentation in vitro. This argues strongly that R. bromii has a pivotal role in fermentation of RS3 in the human large intestine, and that variation in the occurrence of this species and its close relatives may be a primary cause of variable energy recovery from this important component of the diet. This work also indicates that R. bromii possesses an exceptional ability to colonize and degrade starch particles when compared with previously studied amylolytic bacteria from the human colon.
The gut microbiota and its metabolic products interact with the host in many different ways, influencing gut homoeostasis and health outcomes. The species composition of the gut microbiota has been ...shown to respond to dietary change, determined by competition for substrates and by tolerance of gut conditions. Meanwhile, the metabolic outputs of the microbiota, such as SCFA, are influenced both by the supply of dietary components and via diet-mediated changes in microbiota composition. There has been significant progress in identifying the phylogenetic distribution of pathways responsible for formation of particular metabolites among human colonic bacteria, based on combining cultural microbiology and sequence-based approaches. Formation of butyrate and propionate from hexose sugars, for example, can be ascribed to different bacterial groups, although propionate can be formed via alternative pathways from deoxy-sugars and from lactate by a few species. Lactate, which is produced by many gut bacteria in pure culture, can also be utilised by certain Firmicutes to form butyrate, and its consumption may be important for maintaining a stable community. Predicting the impact of diet upon such a complex and interactive system as the human gut microbiota not only requires more information on the component groups involved but, increasingly, the integration of such information through modelling approaches.
The microbial communities that colonize different regions of the human gut influence many aspects of health. In the healthy state, they contribute nutrients and energy to the host via the ...fermentation of nondigestible dietary components in the large intestine, and a balance is maintained with the host's metabolism and immune system. Negative consequences, however, can include acting as sources of inflammation and infection, involvement in gastrointestinal diseases, and possible contributions to diabetes mellitus and obesity. Major progress has been made in defining some of the dominant members of the microbial community in the healthy large intestine, and in identifying their roles in gut metabolism. Furthermore, it has become clear that diet can have a major influence on microbial community composition both in the short and long term, which should open up new possibilities for health manipulation via diet. Achieving better definition of those dominant commensal bacteria, community profiles and system characteristics that produce stable gut communities beneficial to health is important. The extent of interindividual variation in microbiota composition within the population has also become apparent, and probably influences individual responses to drug administration and dietary manipulation. This Review considers the complex interplay between the gut microbiota, diet and health.
Highlights • Diet plays a major role in shaping the gut microbiota both in the short and long-term. • Non-digestible carbohydrates may often stimulate growth of a few specialized species. • Dietary ...impacts upon the gut microbiota influence metabolites that affect health.
Summary
Butyrate‐producing bacteria play an important role in the human colon, supplying energy to the gut epithelium and regulating host cell responses. In order to explore the diversity and ...culturability of this functional group, we designed degenerate primers to amplify butyryl‐CoA:acetate CoA‐transferase sequences from faecal samples provided by 10 healthy volunteers. Eighty‐eight per cent of amplified sequences showed > 98% DNA sequence identity to CoA‐transferases from cultured butyrate‐producing bacteria, and these fell into 12 operational taxonomic units (OTUs). The four most prevalent OTUs corresponded to Eubacterium rectale, Roseburia faecis, Eubacterium hallii and an unnamed cultured species SS2/1. The remaining 12% of sequences, however, belonged to 20 OTUs that are assumed to come from uncultured butyrate‐producing strains. Samples taken after ingestion of inulin showed significant (P = 0.019) increases in Faecalibacterium prausnitzii. Because several of the dominant butyrate producers differ in their DNA % G+C content, analysis of thermal melt curves obtained for PCR amplicons of the butyryl‐CoA:acetate CoA‐transferase gene provides a convenient and rapid qualitative assessment of the major butyrate producing groups present in a given sample. This type of analysis therefore provides an excellent source of information on functionally important groups within the colonic microbial community.
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