Trotta, M.; Agustini, C.; Rohr, C.; Ame, R. M.; Giordano, L.; Balderramo, D.; Romagnoli, P.; vazquez, m.

Carbohydrate-active enzyme (CAZyme) activity in the gut microbiome has significant implications for health, including the release of nutrients otherwise inaccessible to the host and the enhancement of digestive efficiency. The primary end products of indigestible carbohydrate fermentation are short-chain fatty acids (SCFAs). We hypothesized that increased dietary fiber consumption could lead to greater SCFA production in the human gut. To investigate this, we examined the relationship between complex carbohydrate intake, CAZyme activity in the human gut microbiome, and SCFA production at the whole metagenomic level across three cohorts: a healthy reference-controlled cohort, an average cohort of individuals living in industrialized cities, and a cohort of patients with inflammatory bowel disease (IBD). Metagenomic sequencing and bioinformatic analyses were utilized to assess the diversity, abundance, and functionality of CAZymes, as well as the metabolic capacity for SCFA production. The average cohort exhibited higher alpha diversity of CAZyme families compared to the reference-controlled cohort, although subfamily composition was similar between both. A moderate negative correlation was identified between CAZyme abundance and SCFA production, indicating that a higher number of these enzymes does not directly translate to increased SCFA synthesis. In IBD patients, a decrease in the diversity and composition of CAZyme subfamilies was observed, suggesting a disruption in enzymatic functions associated with the disease. However, the overall functionality of CAZymes remained relatively stable across different health conditions, highlighting the resilience of the gut microbiome for these functions. These findings deepen our understanding of the gut microbiome role in health and disease, emphasizing that despite variations in microbial diversity, key enzymatic functions persist. The study underscores the complexity of the non-linear relationship between complex carbohydrate metabolism and SCFA production, laying the groundwork for future research on microbiome-targeted therapeutic/dietary profile interventions in both non-disease and chronic diseases conditions.