Article: Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects
Authors: Marwa Abu El Haija, Yuanchao Ye, Yi Chu, Hussein Herz, Benjamin Linden, Shailesh K Shahi, Kasra Zarei, Ashutosh K Mangalam, Steven J Mcelroy, Mohamad Mokadem
Journal: Surg Obes Relat Dis. 2021 Dec;17(12):1996-2006
Background: Toll-like receptor 4 (TLR4) has been suggested as one of the forefront cross-communicators between the intestinal bacteria and the host to regulate inflammatory signals and energy homeostasis. High-fat diet-induced inflammation is mediated by changes in gut microbiota and requires a functional TLR-4, the deficiency of which renders mice resistant to diet-induced obesity and its associated metabolic dysfunction. Furthermore, gut microbiota was suggested to play a key role in the beneficial effects of Roux-en-Y gastric bypass (RYGB), a commonly performed bariatric procedure.
Objectives: To explore whether TLR4, myeloid differentiation factor 8 (MyD88; 1 of its key downstream signaling regulators) and gut microbiota play an integrative role in RYGB-induced metabolic outcomes.
Setting: Animal- based study.
Method: We performed RYGB in TLR4 and MyD88 knock-out (KO) mice and used fecal microbiota transplant (FMT) from RYGB-operated animals to these genetic mouse models to address our questions.
Results: We demonstrate that RYGB reduces TLR4 expression explicitly in the small and large intestine of C57Blc/6J mice. We also show that TLR4 KO mice have an attenuated glucoregulatory response to RYGB. In addition, we reveal that MyD88 KO mice fail to respond to all RYGB-induced metabolic effects. Finally, fecal microbiota transplant from RYGB-operated mice into TLR4 KO and MyD88 KO naïve recipients fails to induce a metabolic phenotype similar to that of the donors, as it does in wild-type recipients.
Conclusion: TLR4 and MyD88 are required for RYGB-induced metabolic response that is likely mediated by gut microbiome.
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