Faecal microbiota transplantation (FMT) is a promising procedure to restore dysbiosis of the gut microbiota. However, the efficacy and off-target effects of FMT are not yet well established. The gut microbiota exhibits distinct regional differences in composition and function, with the microbiota in the small bowel having a different community and functional impact on the host to the microbiota in the large bowel, which is dominated by anaerobes. Considering these regional differences, it remains unclear whether FMT is suitable to restore the gut microbiota at the regional level within the gut. In a recent study, DeLeon et al. show that regional mismatches between transplanted microbiota and the host gut environment alter the metabolic and immune states of host tissues as well as the composition of regional microbiomes.

The authors hypothesized that mismatches between the post-transplant microbiota and the host gut regional environments lead to changes in the functional output of the microbiome in different regions. To investigate this, they examined the regional metabolomes following microbiota transplant and reported differences in the levels of specific bile acids, carbohydrates and amino acids. Moreover, they found that jejunal and faecal microbiota transplants resulted in distinct systemic circulating metabolite pools in plasma.