Human gut microbiota after bariatric surgery alters intestinal morphology and glucose absorption in mice independently of obesity

• Published in: Gut Vol. 72; no. 3; pp. 460 - 471
• Main Authors: Anhê, Fernando F, Zlitni, Soumaya, Zhang, Song-Yang, Choi, Béatrice So-Yun, Chen, Cassandra Y, Foley, Kevin P, Barra, Nicole G, Surette, Michael G, Biertho, Laurent, Richard, Denis, Tchernof, André, Lam, Tony K T, Marette, Andre, Schertzer, Jonathan
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.03.2023; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Original research
• Subjects: Animal models; Animals; Bariatric Surgery; Blood glucose; Body fat; Body mass index; Catheters; Colonization; Diabetes; diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - surgery; Digestive system; Digestive tract; Feces; Female; Food intake; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal surgery; Germfree; Glucose; glucose metabolism; Glucose tolerance; Gut Microbiota; Humans; Insulin; Insulin Resistance; intestinal absorption; intestinal microbiology; Intestinal microflora; Intestine; Jejunum; Laboratories; Laparoscopy; Mice; Microbiota; Microorganisms; Morphology; Na+/glucose cotransporter; Obesity; Obesity - surgery; Obesity, Morbid - surgery; Patients; Rats; Small intestine; Sodium-glucose cotransporter; Specific pathogen free; Surgery; Vascular surgery; Villus; Weight control; intestinal microbiology; diabetes mellitus; intestinal absorption; obesity surgery; glucose metabolism
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2022-328185

ObjectiveBariatric surgery is an effective treatment for type 2 diabetes (T2D) that changes gut microbial composition. We determined whether the gut microbiota in humans after restrictive or malabsorptive bariatric surgery was sufficient to lower blood glucose.DesignWomen with obesity and T2D had biliopancreatic diversion with duodenal switch (BPD-DS) or laparoscopic sleeve gastrectomy (LSG). Faecal samples from the same patient before and after each surgery were used to colonise rodents, and determinants of blood glucose control were assessed.ResultsGlucose tolerance was improved in germ-free mice orally colonised for 7 weeks with human microbiota after either BPD-DS or LSG, whereas food intake, fat mass, insulin resistance, secretion and clearance were unchanged. Mice colonised with microbiota post-BPD-DS had lower villus height/width and crypt depth in the distal jejunum and lower intestinal glucose absorption. Inhibition of sodium-glucose cotransporter (Sglt)1 abrogated microbiota-transmissible improvements in blood glucose control in mice. In specific pathogen-free (SPF) rats, intrajejunal colonisation for 4 weeks with microbiota post-BPD-DS was sufficient to improve blood glucose control, which was negated after intrajejunal Sglt-1 inhibition. Higher Parabacteroides and lower Blautia coincided with improvements in blood glucose control after colonisation with human bacteria post-BPD-DS and LSG.ConclusionExposure of rodents to human gut microbiota after restrictive or malabsorptive bariatric surgery improves glycaemic control. The gut microbiota after bariatric surgery is a standalone factor that alters upper gut intestinal morphology and lowers Sglt1-mediated intestinal glucose absorption, which improves blood glucose control independently from changes in obesity, insulin or insulin resistance.