Diet Regulates the Engineering of the Gut Microbiota by a Minimal Defined Bacterial Consortium

Meaningfully modifying the gut microbiota in a predictable manner is one way to harness its potential benefits in preventing and/or treating disease. We have recently demonstrated this principle whereby Altered Schaedler Flora (ASF) was used to nucleate a rich microbiota and produce a reduction in ammonia production that had beneficial effects in the setting of liver injury. Since diet alters the composition of the microbiota, herein we investigated the effects of a low protein diet (LPD) on ASF engraftment and its ability to engineer the microbiota. Initially, ASF inoculation was similar between mice fed normal chow or LPD, but the enrichment of microbiota over the next month became strikingly different. Most notable was the inability of the dominant Parabacteroides ASF taxon to exclude other taxa belonging to the Bacteroidetes phylum. Instead, a poorly classified yet highly represented family of Bacteroidetes, S24-7, returned within 4 weeks of inoculation in mice fed a LPD, demonstrating a reduction in ASF resilience in response to dietary stress. Nevertheless, fecal ammonia was sustained at levels significantly lower than those observed in mice on a LPD that received a transplant of normal feces. No deleterious effects were observed in host physiology due to ASF transplantation into mice on LPD. In total, these results demonstrate that diet can have a pronounced effect on engineering the gut microbiota but that these effects may not have significant effects on functionality.