Lactobacillaceae could contribute to the hyperphagia observed in short bowel syndrome: an opening for therapeutic approaches based on the transplantation of simple or complex microbiota?

Short bowel syndrome (SBS), resulting from extensive small bowel resection, is the leading cause of chronic intestinal failure. Patients with SBS spontaneously develop intestinal hyperplasia, hyperphagia and altered gut microbiota. These adaptations reduce dependence on parenteral support, the gold standard of treatment, and therefore improve prognosis and quality of life. In these patients, colonic preservation plays a critical role in energy recovery through fermentation of undigested food by the gut microbiota.

In their paper published in Frontiers in Cellular and Infection Microbiology (March 3rd 2023), Salma Fourati and Johanne Le Beyec of the PIMS research team, led by M. Le Gall & A. Bado, in collaboration with members of JP Hugot’s team, evaluated the feasibility and efficacy of fecal microbiota transplantation (FMT) in SBS rats with jejuno-colic anastomosis.

The transplanted microbiota was obtained from the faeces of rats that had previously been fed an obesogenic diet, which favours a microbiota that is efficient at energy harvesting. Analysis of the microbiota after transplantation showed that the inoculated bacteria were successfully implanted in control rats, but not in SBS rats. This may be explained by the specific luminal environment in SBS colons (higher oxygen, lower pH, etc.) favouring aerotolerant bacteria over transplanted anaerobic bacteria.

FMT had no effect on body weight or food intake in either the control or SBS rats. However, this study was the first to show the development of hyperphagia in an animal model, as observed in patients. In fact, SBS rats doubled their food intake compared to control rats 4 weeks after bowel resection. This food intake was positively correlated with the abundance of Lactobacillaceae in their microbiota, suggesting that this family of bacteria may be involved in the adaptation of feeding behaviour.

This work suggests that signals from the microbiota could contribute to the establishment of adaptation mechanisms, in particular hyperphagia. A therapy based on microbiota transplantation could therefore be of interest if it contains strains of lactobacilli adapted to the specific environment of SBS. The team is now focusing on identifying and testing the best strains to use.