Megasphaera-valerate

Background. The human gut hosts an ecosystem of microbes contributing to the production of short-chain carboxylic acids (SCCA) through fermentation (acetate, butyrate, propionate, formate succinate and lactate) and chain elongation (valerate). This process can be modulated through diet. Valerate is frequently recovered from human fecal samples, but little is known about the microbial contributors and cross-feeding interactions that drive intestinal valerate formation. In this study, we combined co-culture studies and in vitro human fecal microbiota batch fermentations (n=20) with the analysis of a female cohort (n=49) that monitored and modified dairy consumption, to study the role of lactose and lactate in the gut microbial formation of valerate. Results. While the valerate producer Megasphaera elsdenii DSM 20460 was not able to use lactose in single culture, valerate was formed (6.2 ± 1.3 mM) in co-culture with the lactose-utilizing and lactate-producing Streptococcus thermophilus LMG 18311. In vitro, valerate was produced by fecal microbiota of most donors (15/20) in the control medium. Lactose addition increased valerate formation of fecal microbiota that harboured Megasphaera at levels = 4 log cells/mL (n=4), while valerate formation was decreased when Megasphaera < 4 log cells/mL (79%). The addition of M. elsdenii to fecal fermentations increased valerate production in 90% of donors. In vivo, the occurrence of Megasphaera in the cohort participants was higher in women that consumed fermented dairy (18 versus 6 %) compared to those who did not at baseline. Consumption of fermented dairy (intervention and regular consumers) during the three-months study period increased Megasphaera positive carriers (from n=13 to n=16). Intervention with drained yogurt (skyr) led to higher fecal microbial diversity (p<0.05) and relative abundance of Streptococcaceae. Compared to the control group; fecal levels of lactate and valerate were higher (p<0.05) in the intervention group. Both in vitro and in vivo data, with linear regression analysis showed co-occurrence (p<0.05) of the lactate-producer Lactobacillus and Megasphaera. Conclusion. Our findings identified Megasphaera as a key microbe in lactate-driven valerate production. This study brings forward new mechanistic understanding of the intestinal microbial formation of the SCCA valerate during fermented dairy consumption.