In-depth characterization of a selection of gut commensal bacteria reveals their functional capacities to metabolize dietary carbohydrates with prebiotic potential.

The microbial utilization of dietary carbohydrates is closely linked to the pivotal role of the gut microbiome in human health. Inherent to the modulation of complex microbial communities, a prebiotic implies the selective utilization of a specific substrate, relying on the metabolic capacities of targeted microbes. In this study, we investigated the metabolic capacities of 17 commensal bacteria of the human gut microbiome toward dietary carbohydrates with prebiotic potential. First, in vitro experiments allowed the classification of bacterial growth and fermentation profiles in response to various carbon sources, including agave inulin, corn fiber, polydextrose, and citrus pectin. The influence of phylogenetic affiliation appeared to statistically outweigh carbon sources in determining the degree of carbohydrate utilization. Second, we narrowed our focus on six commensal bacteria representative of the Bacteroidetes and Firmicutes phyla to perform an untargeted high-resolution liquid chromatography-mass spectrometry metabolomic analysis: Bacteroides xylanisolvens, Bacteroides thetaiotaomicron, Bacteroides intestinalis, Subdoligranulum variabile, Roseburia intestinalis, and Eubacterium rectale exhibited distinct metabolomic profiles in response to different carbon sources. The relative abundance of bacterial metabolites was significantly influenced by dietary carbohydrates, with these effects being strain-specific and/or carbohydrate-specific. Particularly, the findings indicated an elevation in short-chain fatty acids and other metabolites, including succinate, gamma-aminobutyric acid, and nicotinic acid. These metabolites were associated with putative health benefits. Finally, an RNA-Seq transcriptomic approach provided deeper insights into the underlying mechanisms of carbohydrate metabolization. Restricting our focus on four commensal bacteria, including B. xylanisolvens, B. thetaiotaomicron, S. variabile, and R. intestinalis, carbon sources did significantly modulate the level of bacterial genes related to the enzymatic machinery involved in the metabolization of dietary carbohydrates. This study provides a holistic view of the molecular strategies induced during the dynamic interplay between dietary carbohydrates with prebiotic potential and gut commensal bacteria. IMPORTANCE: This study explores at a molecular level the interactions between commensal health-relevant bacteria and dietary carbohydrates holding prebiotic potential. We showed that prebiotic breakdown involves the specific activation of gene expression related to carbohydrate metabolism. We also identified metabolites produced by each bacteria that are potentially related to our digestive health. The characterization of the functional activities of health-relevant bacteria toward prebiotic substances can yield a better application of prebiotics in clinical interventions and personalized nutrition. Overall, this study highlights the importance of identifying the impact of prebiotics at a low resolution of the gut microbiota to characterize the activities of targeted bacteria that can play a crucial role in our health.

Prebiotics and the Human Gut Microbiota: From Breakdown Mechanisms to the Impact on Metabolic Health.

The colon harbours a dynamic and complex community of microorganisms, collectively known as the gut microbiota, which constitutes the densest microbial ecosystem in the human body. These commensal gut microbes play a key role in human health and diseases, revealing the strong potential of fine-tuning the gut microbiota to confer health benefits. In this context, dietary strategies targeting gut microbes to modulate the composition and metabolic function of microbial communities are of increasing interest. One such dietary strategy is the use of prebiotics, which are defined as substrates that are selectively utilised by host microorganisms to confer a health benefit. A better understanding of the metabolic pathways involved in the breakdown of prebiotics is essential to improve these nutritional strategies. In this review, we will present the concept of prebiotics, and focus on the main sources and nature of these components, which are mainly non-digestible polysaccharides. We will review the breakdown mechanisms of complex carbohydrates by the intestinal microbiota and present short-chain fatty acids (SCFAs) as key molecules mediating the dialogue between the intestinal microbiota and the host. Finally, we will review human studies exploring the potential of prebiotics in metabolic diseases, revealing the personalised responses to prebiotic ingestion. In conclusion, we hope that this review will be of interest to identify mechanistic factors for the optimization of prebiotic-based strategies.