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

• Published in: Molecular metabolism (Germany) Vol. 42; p. 101076
• Main Authors: Hartstra, Annick V., Schüppel, Valentina, Imangaliyev, Sultan, Schrantee, Anouk, Prodan, Andrei, Collard, Didier, Levin, Evgeni, Dallinga-Thie, Geesje, Ackermans, Mariette T., Winkelmeijer, Maaike, Havik, Stefan R., Metwaly, Amira, Lagkouvardos, Ilias, Nier, Anika, Bergheim, Ina, Heikenwalder, Mathias, Dunkel, Andreas, Nederveen, Aart J., Liebisch, Gerhard, Mancano, Giulia, Claus, Sandrine P., Benítez-Páez, Alfonso, la Fleur, Susanne E., Bergman, Jacques J., Gerdes, Victor, Sanz, Yolanda, Booij, Jan, Kemper, Elles, Groen, Albert K., Serlie, Mireille J., Haller, Dirk, Nieuwdorp, Max
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.12.2020; Elsevier
• Subjects: Gut-brain axis; Gutmicrobiota; Metabolites; Obesity; Original; Obesity; Metabolites; Gutmicrobiota; Gut-brain axis
• ISSN: 2212-8778; 2212-8778
• DOI: 10.1016/j.molmet.2020.101076

Increasing evidence indicates that intestinal microbiota play a role in diverse metabolic processes via intestinal butyrate production. Human bariatric surgery data suggest that the gut-brain axis is also involved in this process, but the underlying mechanisms remain unknown. We compared the effect of fecal microbiota transfer (FMT) from post-Roux-en-Y gastric bypass (RYGB) donors vs 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. Plasma metabolites and fecal microbiota were also determined at these time points. We observed an increase in brain DAT after donor FMT compared to oral butyrate that reduced this binding. However, no effect on body weight and insulin sensitivity was demonstrated after post-RYGB donor feces transfer in humans with metabolic syndrome. Increases in fecal levels of Bacteroides uniformis were significantly associated with an increase in DAT, whereas increases in Prevotella spp. showed an inverse association. Changes in the plasma metabolites glycine, betaine, methionine, and lysine (associated with the S-adenosylmethionine cycle) were also associated with altered striatal DAT expression. Although more and larger studies are needed, our data suggest a potential gut microbiota-driven modulation of brain dopamine and serotonin transporters in human subjects with obese metabolic syndrome. These data also suggest the presence of a gut-brain axis in humans that can be modulated. 4488. What is already known about this subject?•Gut microbiota are involved in human health and metabolic disease.•Changes in gut microbiota are associated with brain disease.•Animal studies have suggested that fecal transplantation can alter brain (dopamine and serotonin) metabolism. What are the new findings?•Donor fecal microbiota transplantation affects (123I-FP-CIT-determined) cerebral serotonin transporters (SERT) and dopamine transporters (DAT) in obese humans with metabolic syndrome.•These differential changes are accompanied by alterations in plasma metabolites and fecal microbiota composition.•New correlations between changes in microbiota strains and plasma metabolites in relation to the gut-brain axis in human obesity are observed. How might it impact on clinical practice in the foreseeable future?•This study helps to quantify the magnitude of gut microbiota-driven effects on human serotonin and dopamine in obese humans.•This study provides a rationale for future sample size calculations for FMT trials in manipulating the gut-brain axis through gut microbiota interventions.•This study provides a rationale for future sample size calculations for FMT trials in manipulating the gut-brain axis through gut microbiota interventions.