High fat and high protein foods have been studied in various health outcomes and diseases. For example, high fat foods that come close to eliminating all carbohydrates can induce a state of ketosis. Ketosis is characterized by the production of ketone bodies and has been associated with weight loss, insulin resistance, reduced inflammation, and shifts in the gut microbiome. As a result, these foods are used to manage conditions such as epilepsy and obesity, yet we still lack information on their mechanism of effect via the gut microbiome, particularly with respect to small molecule chemistry and shifts to gut microbiome metabolism.
We conducted a randomized cross-over study to understand the interaction of low-carb foods with the gut ecosystem in canines. Thirty-five healthy dogs were fed three different foods varying in fat and protein sources over 5 weeks each. Initially, all dogs were given a balanced (25%/37%/38% protein/fat/carb as percent of total metabolizable energy). They were then randomly assigned to one of two low carbohydrate foods: high-protein (53%/39%/8%) or high-fat (27%/68%/5%) for 5 weeks before switching to the other food for the final 5 weeks. Stool and blood samples collected at each 5-week interval underwent metabolome profiling, with stool samples also used for metagenomic sequencing.
We observed strong associations between food and overall fecal and serum chemical composition, as well as gut microbiome composition (p < 0.05). Bifidobacteria spp. were significantly reduced during consumption of both low-carb foods, whereas most Firmicutes increased. For instance, Peptostreptococcaceae SGB6132 was almost always present during low-carb food consumption and absent otherwise. In addition to broad taxonomic changes, we also found that several microbially associated metabolites shifted in abundance in response to differing low-carb diets. For example, we observed changes in pathways related to tryptophan metabolism, secondary bile acid metabolism, and short-chain fatty acid fermentation. Both low-carb diets reduced fecal levels of butyrate, while increasing levels of branched-chain fatty acids such as isobutyric acid and 2-methylbutyric acid (p < 0.05). Fecal amino acid levels decreased during low-carb foods, particularly when carbs were replaced with fat. Moreover, we identified similar decreases in fecal dipeptides, alongside increased fecal ammonia levels, suggesting elevated protein catabolism. This was associated with various microbial taxa, including a previously unidentified species in the Oscillospiraceae family.
Overall, we found that low-carb diets significantly alter gut microbiome communities and shift metabolite profiles within the gut, potentially towards increased protein catabolism. These findings highlight the potential for further mechanistic investigations and underscore the importance of microbial metabolism in the health effects of low-carb diets.