Infusion of donor feces affects the gut-brain axis in humans with metabolic syndrome

Objectives: There is increasing evidence that intestinal microbiota play a role in diverse metabolic processes via intestinal butyrate production. Based on bariatric surgery data in humans it has been suggested that the gut-brain axis is also involved in this process, however the underlying mechanisms are still unknown.

Design: We therefore compared the effect of fecal microbiota transfer (FMT) from post-Roux-en-Y gastric bypass (RYGB) donors versus oral butyrate supplementation on (¹²³I-FP-CIT determined) brain dopamine transporter (DAT) and serotonin transporter (SERT) binding as well as stable isotope determined insulin sensitivity at baseline and after 4 weeks in 24 male and female treatment-naïve metabolic syndrome subjects. Also, plasma metabolites and fecal microbiota were determined at these timepoints.

Results: We observed an increase in brain DAT upon donor FMT compared to oral butyrate that reduced this binding. However, no effect on body weight and insulin sensitivity was seen upon post-RYGB donor feces transfer in either humans with metabolic syndrome. In line, increases in fecal levels of Bacteroides uniformis were significantly associated with an increase in DAT whereas increases in Prevotella spp. showed an inverse association. Furthermore, changes in the plasma metabolites glycine, betaine, methionine and lysine (associated with the S-adenosylmethionine cycle) were also associated with altered striatal DAT expression.

Conclusion: Although more and larger studies are needed, our data suggest a potential gut microbiota-driven modulation of brain dopamine and serotonin transporters in human obese metabolic syndrome subjects. Moreover, these data suggest the presence of a gut-brain axis in humans,that can be modulated. NTR registration: 4488.