Interplay between the human gut microbiome and host metabolism

Abstract

The human gut is inhabited by a complex and metabolically active microbial ecosystem regulating host health. While many studies have focused on the effect of individual microbial taxa, the metabolic potential of the entire gut microbial ecosystem has been largely under-explored. We characterised the gut microbiome of 1,004 twins via whole shotgun metagenomic sequencing (average 39M reads per sample). We observed greater similarity, across unrelated individuals, for functional metabolic pathways (82%) than for taxonomic composition (43%). We conducted a microbiota-wide association study linking both taxonomic information and microbial metabolic pathways with 673 blood and 713 faecal metabolites (Metabolon, Inc.). Metabolic pathways associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species-level results identified less than 3,000 associations, suggesting that coordinated action of multiple taxa is required to affect the metabolome. Finally, we estimated that the microbiome mediated a crosstalk between 71% of faecal and 15% of blood metabolites, highlighting six key species (unclassified Subdoligranulum spp., Faecalibacterium prausnitzii, Roseburia inulinivorans, Methanobrevibacter smithii, Eubacterium rectale, and Akkermansia muciniphila). Because of the large inter-person variability in microbiome composition, our results underline the importance of studying gut microbial metabolic pathways rather than focusing purely on taxonomy to find therapeutic and diagnostic targets.

Temporal dynamics of the gut microbiome and metabolome in preterm and term infants from birth through the first year of life

“…In comparison to gut microbial composition, the metabolic profiles were relatively less sensitive to the infant development in terms of sampling time points. Temporal stability of the gut metabolome can be related to the concept of high redundancy of metabolic pathways across different microbial species (33,34). Our finding is also in line with previous literature suggesting that human metabolic profiles are more conserved than gut microbiome (34).…”

“…Temporal stability of the gut metabolome can be related to the concept of high redundancy of metabolic pathways across different microbial species (33,34). Our finding is also in line with previous literature suggesting that human metabolic profiles are more conserved than gut microbiome (34). Elevated serum MMA and stool glucose have been associated with vitamin B12 (35) and carbohydrate malabsorption (36) in children respectively.…”

Gut microbiota of obese subjects with Prader-Willi syndrome is linked to metabolic health

“…38 In addition, the abundance of M. smithii has been recently found to correlate negatively with the percentage of visceral fat. 39 Another large population study reported that Akkermansia, Christensenellaceae, the Tenericutes RF39 and Rikenellaceae are associated with lower serum triglycerides levels in addition to low BMI. 40 Interestingly, we found that the increase of the Archaea Methanobrevibacter and vadinCA11, and the decrease of the genus Dorea, are specifically associated with PWS, and not dependent on BFMI.…”

The crosstalk between microbiome and asthma: Exploring associations and challenges

“…The microbiome is thought to have host genetic background, cause epigenetic modulations, affect host metabolism and be influenced by environmental exposures . This necessitates integrating the microbiome with other omics layers, such as metabolomics, proteomics, transcriptomics, genomics, epigenomics and exposomics (environmental factors), which will help to provide more insight into the mechanisms of complex disease processes such as asthma.…”