Intestinal expression of toll-like receptor gene changes early after gastric bypass surgery and association with type 2 diabetes remission

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2020-11, Vol.79-80, p.110885-110885, Article 110885
• Main Authors: Sala, Priscila, Torrinhas, Raquel Susana Matos de Miranda, Fonseca, Danielle C., Machado, Natasha Mendonça, Singer, Joelle, Singer, Pierre, Ravacci, Graziela Rosa, Belarmino, Giliane, Ferreira, Beatriz A.M., Marques, Mariane, Ishida, Robson Kiyoshi, Guarda, Ismael Francisco Mota Siqueira, de Moura, Eduardo Guimarães Hourneaux, Sakai, Paulo, Santo, Marco Aurélio, Sunaga, Daniele Yumi, Heymsfield, Steven B., Bezerra, Daniele Pereira dos Santos, Corrêa-Giannella, Maria Lúcia, Waitzberg, Dan Linetzky
• Format: Article
• Language: English
• Subjects: Bariatric surgery; Biomarkers; Biopsy; Body mass index; Body weight loss; Cholesterol; Correlation; Diabetes; Diabetes mellitus (non-insulin dependent); Digestive system; DNA microarrays; Dysbacteriosis; Energy; Energy balance; Gastric bypass; Gastrointestinal surgery; Gastrointestinal tract; Gene expression; Genes; Homeostasis; Inflammation; Insulin resistance; Intestinal bypass; Intestinal microflora; Intestine; Lipoproteins; Metabolism; Microbiota; Obesity; Patients; Peptides; Permeability; Polymerase chain reaction; Principal components analysis; Receptors; Remission; Remission (Medicine); Standard deviation; Surgery; TLR4 protein; TLR7 protein; Toll-like receptors; Triglycerides; Type 2 diabetes; Weight loss
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2020.110885

Abnormal activation of toll-like receptors (TLRs) is observed in obese rodents and is correlated with local dysbiosis and increased gut permeability. These purported changes trigger systemic inflammation associated with obesity-related comorbidities, including type 2 diabetes (T2D). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for severe obesity and known to induce changes in the gut microbiota and decrease systemic inflammation in humans. This study examined the intestinal expression of TLR-encoding genes in obese women (n = 20) treated with RYGB surgery and the relationship of these genes with T2D remission (T2Dr Intestinal biopsies were performed before and 3 months after RYGB surgery. Partial and complete T2Dr after 1 year was assessed using the American Diabetes Association criteria. Affymetrix Human GeneChip 1.0 ST array (microarray) and TaqMan assay (real-time quantitative polymerase chain reaction) were used to analyze intestinal gene expression, and associations with systemic markers of energy homeostasis were examined. Patients experienced significant weight loss (P < 0.001) and altered gut TLR gene expression 3 months after surgery. The main effects were a reduction in jejunal TLR4 expression in patients with complete and partial T2Dr (P < 0.05). There was a postoperative decrease in jejunal TLR7 expression in patients with complete T2Dr that correlated inversely with high-density lipoprotein cholesterol and positively with triglyceride concentrations, but not with weight loss. RYGB-induced weight loss–independent changes in the expression of intestinal TLR-encoding genes in obese women and complete T2Dr that was correlated with systemic markers of energy homeostasis. The modulation of intestinal TLRs may mediate inflammatory mechanisms linked to T2Dr after RYGB surgery. •In obesity models, abnormal toll-like receptor (TLR) activation by dysbiosis increases gut permeability•Gut dysbiosis and permeability have been associated with chronic inflammation in type 2 diabetes•Roux-en-Y gastric bypass (RYGB) surgery influences gut microbiota and can lead to the remission of obesity-related type 2 diabetes•Decreases in gut TLR-4 and TLR-7 expression were observed after RYGB surgery•Decreased gut TLR expression may be enrolled in post-RYGB surgery glycemic homeostasis