Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes

Abstract

Akkermansia muciniphila is a Gram-negative anaerobic mucus-layer-degrading bacterium that colonizes the intestinal mucosa of humans and rodents. Metagenomic data have shown an inverse correlation between the abundance of A. muciniphila and diseases such as inflammatory bowel disease (IBD), obesity, and diabetes. Thus, in recent decades, the potential of this bacterium as an immunomodulatory probiotic for autoimmune and chronic inflammatory diseases has been explored in experimental models. Corroborating these human correlation data, it has been reported that A. muciniphila slows down the development and progression of diabetes, obesity, and IBD in mice. Consequently, clinical studies with obese and diabetic patients are being performed, and the preliminary results are very promising. Therefore, this mini review highlights the main findings regarding the beneficial roles of A. muciniphila and its action mechanisms in autoimmune and chronic inflammatory diseases.

Keywords: Akkermansia muciniphila; diabetes; gut dysbiosis; inflammatory bowel diseases; obesity.

Figure 1

Regulatory effects of A. muciniphila on obesity, T2D, and T1D. In the models of diet-induced obesity (DIO), oral treatment with A. muciniphila reduces weight gain, controls fat accumulation, increases regulatory T cells (T regs), and decreases the production of pro-inflammatory cytokines in the adipose tissue of mice fed with a high-fat diet (HFD). In the intestine, this probiotic increases goblet cells and mucus production, in addition to inducing a greater production of glucagon-like peptide-1 (GLP-1), which controls glucose absorption. The administration of pasteurized A. muciniphila to obese subjects decreased body weight and hip circumference, improved insulin sensitivity, and reduced the markers of liver damage. In NOD mice, the model of T1D (autoimmune), A. muciniphila improved mucus production and increased the antimicrobial peptide RegIIIγ, which contributes to improved intestinal barrier function and the lower translocation of LPS into the circulation. In parallel, the probiotic increases the production of anti-inflammatory cytokines in pancreatic lymph nodes (PLNs) and potentiates the recruitment of T regs in the pancreas, culminating in a delay in the development of T1D. Vancomycin-treated NOD mice showed an enrichment of A. muciniphila in the gut, which is correlated with a lower degree of insulitis and glycemic control. Figure created with BioRender.com. TNF-α: tumor necrosis factor-α; IL-6: interleukin-6, GLP-1: glucagon-like peptide-1; GLUT2, glucose transporter 2; SGLT1, sodium-glucose cotransporter 1; GLUT5, glucose transporter 5; RegIIIγ: regeneration islet-derived III, IL-10: inyerleukin-10; TGF-β, transforming growth factor beta; TLR2/4, Toll-like receptor 2/4; TJs, tight junctions.