Daily fluctuation of colonic microbiome in response to nutrient substrates in a pig model.

Studies on rodents indicate the daily oscillations of the gut microbiota have biological implications for host. However, the responses of fluctuating gut microbes to the dynamic nutrient substrates are not fully clear. In the study, we found that the feed intake, nutrient substrates, microbiota and metabolites in the colon underwent asynchronous oscillation within a day. Short-chain fatty acids (SCFAs) including acetate, propionate, butyrate and valerate peaked during T24 ~ T27 (Timepoint 24, 12:00 pm, T27, 03:00 am) whereas branched SCFAs isobutyrate and isovalerate peaked during T09 ~ T12. Further extended local similarity analysis (eLSA) revealed that the fluctuation of feed intake dynamically correlated with the colonic carbon substrates which further influenced the oscillation of sugar metabolites and acetate, propionate, butyrate and valerate with a certain time shift. The relative abundance of primary degrader Ruminococcaceae taxa was highly related to the dynamics of the carbon substrates whereas the fluctuations of secondary degraders Lactobacillaceae and Streptococcaceae taxa were highly correlated with the sugar metabolites. Meanwhile, colonic nitrogen substrates were correlated with branched amino acids and the branched SCFAs. Furthermore, we validated the evolution of gut microbes under different carbohydrate and protein combinations by using an in vitro fermentation experiment. The study pictured the dynamics of the micro-ecological environment within a day which highlights the implications of the temporal dimension in studies related to the gut microbiota. Feed intake, more precisely substrate intake, is highly correlated with microbial evolution, which makes it possible to develop chronotherapies targeting the gut microbiota through nutrition intervention.