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The bioavailability of catechin highly relies on gut microbiota which may determine its metabolic profile, resulting in different health outcomes. Here, we investigated in vitro (+)-catechin metabolism by human microbial communities. There were substantial interindividual differences in the metabolic profiles of (+)-catechin, with 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone being the major contributor. Furthermore, the microbial metabolic rate of catechin enabled stratification of 12 participants (fast, medium, and slow converters), despite the interference from the strong intrinsic interindividual variability in fecal microbiota. Correlations were established between this stratified population and microbiota features, such as ecosystem diversity. Additionally, fast converters had significantly higher prevalences of amplicon sequence variants (ASVs) with potential capacity of C-ring cleavage (ASV233_Eggerthella and ASV402_Eubacterium), B-ring dihydroxylation (ASV402_Eubacterium), and short-chain fatty acid (SCFA)-producing ASVs. In conclusion, metabolic-capability-based stratification allows us to uncover differences in microbial composition between fast and slow converters, which could help to elucidate interindividual variabilities in the health benefits of catechins.

Inter-individual variability in the microbial gene complement encoding for carbohydrate-active enzymes (CAZymes) can profoundly regulate how the host interacts with diverse carbohydrate sources thereby influencing host health. CAZy-typing, characterizing the microbiota-associated CAZyme-coding genes within a host individual, can be a useful tool to predict carbohydrate pools that the host can metabolize, or identify which CAZyme families are underrepresented requiring supplementation via microbiota transplantation or probiotics. CAZy-typing, moreover, provides a novel framework to search for disease biomarkers. As a proof of concept, we used publicly available metagenomes (935) representing 310 type strain bacterial genomes to establish the link between disease status and CAZymes in the oral and gut microbial ecosystem. The abundance and distribution of 220 recovered CAZyme families in saliva and stool samples from patients with colorectal cancer, rheumatoid arthritis, and type 1 diabetes were compared with healthy subjects. Based on the multivariate discriminant analysis, the disease phenotype did not alter the CAZyme profile suggesting a functional conservation in carbohydrate metabolism in a disease state. When disease and healthy CAZyme profiles were contrasted in differential analysis, CAZyme markers that were underrepresented in type 1 diabetes (15), colorectal cancer (12), and rheumatoid arthritis (5) were identified. Of interest, are the glycosyltransferase which can catalyze the synthesis of glycoconjugates including lipopolysaccharides with the potential to trigger inflammation, a common feature in many diseases. Our analysis has also confirmed the expansive carbohydrate metabolism in the gut as evidenced by the overrepresentation of CAZyme families in the gut compared to the oral site. Nevertheless, each site exhibited specific CAZyme markers. Taken together, our analysis provides an insight into the CAZyme landscape in health and disease and has demonstrated the diversity in carbohydrate metabolism in host-microbiota which can be a sound basis for optimizing the selection of pre, pro, and syn-biotic candidate products.

This study compares the metabolic properties of kojibiose, trehalose, sucrose and xylitol upon incubation with representative oral bacteria as monocultures, synthetic communities or with human salivary bacteria in a defined medium. As compared to sucrose and trehalose, kojibiose resisted metabolism during a 48h incubation with monocultures, except for Actinomyces viscosus. Incubations with Lactobacillus spp. based communities, as well as salivary bacteria displayed kojibiose metabolism, yet to a lesser extent than sucrose and trehalose. Concurring with our in vitro findings, screening for carbohydrate active enzymes revealed that only Lactobacillus spp. and A. viscosus possess enzymes from glycohydrolase (GH) families GH65 and GH15 respectively that are associated with kojibiose metabolism. Donor-dependent differences in salivary microbiome composition were noted and differences in pH drop during incubation indicated different rates of sugar metabolism. Yet, functional analysis indicated lactate, acetate and formate to evenly dominate the metabolic profile for all sugars except for xylitol. 16S rRNA gene sequencing analysis and α-diversity markers revealed that significant shift of microbiome community by sugars was more pronounced in sucrose and trehalose than in kojibiose and xylitol. Streptococcus spp. a taxon linked to cariogenesis dominated in sucrose (91.8±6.4%) and trehalose (55.9±38.6%) representing a high diversity loss. In contrast, Streptococcus (5.1±3.7%) was less abundant in kojibiose which instead was dominated by Veillonella (26.8±19.6%) while for xylitol Neisseria (29.4±19.1%) was most abundant. Overall, kojibiose and xylitol incubations less stimulated cariogenic species yet closely maintained an abundance of key phyla and genera of salivary microbiome, suggesting that kojibiose has low cariogenic properties. IMPORTANCE This study provides a detailed scientific insight on the metabolism of a rare disaccharide; kojibiose whose mass production methodology has recently been made possible. While the resistance of kojibiose was established with monocultures, a delayed utilization of kojibiose was observed with communities containing lactobacilli and A. viscosus as well as with complex communities of bacteria from human saliva. Kojibiose is therefore, less metabolizable as compared to sucrose and trehalose. Moreover, although conventional sugars cause distinct shifts in salivary microbial communities, our study has revealed that kojibiose is able to closely maintain the salivary microbiome composition suggesting its low cariogenic properties. This study furthermore underscores the importance and relevance of microbial culture and ex vivo mixed cultures to study cariogenicity and substrate utilization, this is in sharp contrast with tests that solely rely on monocultures such as S. mutans, which clearly fail to capture complex interaction between oral microbiota.

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