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

Abstract

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.

Keywords: carbohydrate metabolism; gut microbiota; health and well-being; personalised nutrition; prebiotics; short-chain fatty acids.

Figure 1

Nutrient acquisition strategies in two common trophic behaviours. The archetypal starch utilisation system (SUS) operon, a model system for starch uptake described in the commensal Bacteroides thetaiotaomicron at the origin of the polysaccharide utilisation locus (PUL). Intimately associated, the SusD cell-surface glycan binding proteins (SGBPs) initially adhere to and recruit the substrate from the outer membrane. The SusG endoglucanase proteins (GHs and PLs) hydrolyse starch into smaller malto-oligosaccharides that are further imported into the periplasm by the SusC Ton-B dependent transporter (TBDT). Carbohydrate-binding proteins and endoglucanase proteins vary substantially between PULs. Subsequently, oligosaccharides are catalysed into single sugars by the SusA and SusB exoglucosidases in the periplasmic space, before being imported into the cytoplasm for primary metabolism. In response to the presence of malto-oligosaccharides, the prototypic PUL regulator SusR protein senses degradation products to control the transcriptional activation of the PUL machinery. In the intestinal environment, the products of carbohydrate breakdown can be either slotted into primary metabolic pathways, which could be called selfish behaviour, or act for the public good. These latter show cooperative behaviour, where polymers and hydrolytic enzymes can simply diffuse or can be shared in outer membrane vesicles (OMVs). P, phosphorus; H⁺, hydrogen ions; SusA–SusD, SusG, SusR, SUS homologs; TonB, ExbB, ExbD, outer membrane receptors.

Figure 2

Short-chain fatty acid (SCFA) biosynthesis pathways by the gut microbiota. The different pathways involved in SCFA production are presented for acetate, butyrate, and propionate. SCFA-producing bacteria for each pathway are also shown. Acetate is mainly produced in the gut from pyruvate via acetyl-coenzyme A (CoA). Three pathways have been described for propionate synthesis, namely acrylate, succinate, and propanediol. The first two start from phosphoenolpyruvate (PEP) and the latter uses deoxysugars, such as fucose and rhamnose. Butyrate is produced via two pathways: the butyryl-CoA: acetate CoA-transferase and the butyrate kinase.

Figure 3

The determination of individual characteristics to direct an efficient prebiotic intervention. Individual and environmental shaping factors and interindividual variability of microbiomes modulate differential clinical responses to prebiotics. The description of microbiome signatures at the compositional and functional levels can provide insights to define a targeted nutritional strategy. A standardisation of multi-criteria aims to match the prebiotic intervention with individuals that would likely respond efficiently.