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

Abstract

Objective 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. Methods We compared the effect of fecal microbiota transfer (FMT) from post-Roux-en-Y gastric bypass (RYGB) donors vs oral butyrate supplementation on ( 123 I-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. Results 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. Conclusions 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. NTR registration 4488.

Contribution of Gut Microbiota to Immunological Changes in Alzheimer’s Disease

“…So far, no studies have investigated the effect of FMT in AD patients. However, an effect of FMT on the brain was demonstrated in obese patients, where FMT increased dopamine transporter binding which was associated with an concomitant increase in Bacteroides uniformis ( 174 ).…”

Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future?

“…This is important as adverse metabolic traits can be transferred (de Groot et al, 2020a). In this regard, it is also likely that the metabolic phenotype of the FMT donor can affect gut-brain axis in human subjects (Hartstra et al, 2020).…”

“…It is also increasingly appreciated that gut microbes may produce a range of metabolites that alter human behaviors, either directly by metabolites that pass the blood-brain barrier, or indirectly through modulation of the autonomous nervous activity of the gut leading to altered satiety and mood. FMTs may therefore target the gut-brain axis (Figure 4F), regulating metabolites associated with mood and satiety, key players in the development of insulin resistance (Hartstra et al, 2020).…”

The Role of the Gut Microbiota in the Gut–Brain Axis in Obesity: Mechanisms and Future Implications

“…Furthermore, ex vivo treatment of human adipose tissue biopsies with propionic acid increased the expression of the anorexigenic hormone leptin and reduced inflammatory factors [ 78 , 79 ]. Most studies in humans are associative, and our group recently showed that oral administration of SCFA butyrate does not improve glucose metabolism or vagal tone in metabolic syndrome subjects [ 76 , 80 ]. Additional human trials are needed to further identify the possible role of other SCFAs as intervention in obesity and obesity-related metabolic disorders.…”

“…The role of serotonin in obesity is complex, and the role the microbiota have on central serotonin is still unclear. However, our recent pilot study using SPECT imaging in humans suggested that the gut microbiota can directly or indirectly affect brain serotonin (and dopamine) transporter binding potential in humans with obesity via sympathetic tone [ 80 ].…”