Microbial metabolites: cause or consequence in gastrointestinal disease?

Abstract

Systems biology studies have established that changes in gastrointestinal microbiome composition and function can adversely impact host physiology. Notable diseases synonymously associated with dysbiosis include inflammatory bowel diseases, cancers, metabolic disorders, opportunistic and recurrent pathogen infections. However, there is a scarcity of mechanistic data that advances our understanding of taxonomic correlations with pathophysiologic host-microbiome interactions. Generally, in order to survive a hostile gut environment, microbes are highly metabolically active and produce trans-kingdom signaling molecules to interact with competing microorganisms and the host. These specialized metabolites likely play important homeostatic roles and identifying disease-specific taxa and their effector pathways can provide better strategies for diagnosis, treatment, and prevention, as well as the discovery of innovative therapeutics. The signaling role of microbial biotransformation products such as bile acids, short chain fatty acids, polysaccharides and dietary tryptophan is increasingly recognized, but little is known about the identity and function of metabolites that are synthetized by microbial biosynthetic gene clusters. Here we consider how bioactive natural products directly encoded by the human microbiome can contribute to the pathophysiology of gastrointestinal disease, cancer, autoimmune, antimicrobial-resistant bacterial and viral infections (including COVID-19). We also present strategies used to discover these compounds and the biological activities they exhibit, with consideration of therapeutic interventions that could emerge from understanding molecular causation in gut microbiome research.

Multiomics and quantitative modelling disentangle diet, host, and microbiota contributions to the host metabolome

“…Other enrichments are diet-specific: for example, fatty acid esters were enriched in Group VIII (positive cecum host metabolism parameter on HFD), whereas organic sulfides and sulfoxides were enriched in Group IX (positive cecum host metabolism parameter on HCD), consistent with expected host metabolism products of the corresponding diet ingredients. Metabolites from Group X (characterized by a high microbial metabolism parameter) were enriched in organic acids, benzenoids, carbonyl compounds and polyketides, which is in line with prior reports of microbiota-associated compounds 44–47 .…”

Inhibition of the Occurrence and Development of Inflammation-Related Colorectal Cancer by Fucoidan Extracted from Sargassum fusiforme

“…In addition, intestinal microbial dysbiosis and impaired intestinal barrier are key to this inflammatory process. 7 Although the causal relationship between microorganisms and their metabolites and intestinal diseases is not yet fully understood, 32 under normal circumstances, intestinal microbes maintain a dynamic balance. Once this balance is upset, an increase in the number of "bad" microbes may exacerbate intestinal inflammation.…”

The Diversity of Gut Microbiota at Weaning Is Altered in Prolactin Receptor-Null Mice

“…Most terpenoids are terpene derivatives not encoded by microbiome genomes but represent microbial metabolites from dietary products or bile acid derivatives, and some of them are the result of the activities of oxidizing enzymes, such as terpene cyclases or synthases, and the addition of carbohydrates, amino acids, and fatty acid chains into polycyclic terpene backbones [66,67]. Some terpenes are widely synthesized by Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes and display a wide range of biological properties, but little information regarding their colonic biosynthesis and effects has been reported [68]. On the other hand, polyketides are secondary metabolites produced mainly by Actinobacteria, Proteobacteria, Bacteroidetes, and Firmicutes, and they exhibit antimicrobial properties against select populations [69].…”