Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice

Abstract

Abnormal shifts in the composition of gut microbiota contribute to the pathogenesis of metabolic diseases, including obesity and type 2 diabetes (T2DM). The crosstalk between gut microbes and the host affects the inflammatory status and glucose tolerance of the individuals, but the underlying mechanisms have not been elucidated completely. In this study, we treated the lean chow diet-fed mice with Akkermansia muciniphila, which is thought to be inversely correlated with inflammation status and body weight in rodents and humans, and we found that A. muciniphila supplementation by daily gavage for five weeks significantly alleviated body weight gain and reduced fat mass. Glucose tolerance and insulin sensitivity were also improved by A. muciniphila supplementation compared with the vehicle. Furthermore, A. muciniphila supplementation reduced gene expression related to fatty acid synthesis and transport in liver and muscle; meanwhile, endoplasmic reticulum (ER) stress in liver and muscle was also alleviated by A. muciniphila. More importantly, A. muciniphila supplementation reduced chronic low-grade inflammation, as reflected by decreased plasma levels of lipopolysaccharide (LPS)-binding protein (LBP) and leptin, as well as inactivated LPS/LBP downstream signaling (e.g. decreased phospho-JNK and increased IKBA expression) in liver and muscle. Moreover, metabolomics profiling in plasma also revealed an increase in anti-inflammatory factors such as α-tocopherol, β-sitosterol and a decrease of representative amino acids. In summary, our study demonstrated that A. muciniphila supplementation relieved metabolic inflammation, providing underlying mechanisms for the interaction of A. muciniphila and host health, pointing to possibilities for metabolic benefits using specific probiotics supplementation in metabolic healthy individuals.

Black Raspberries and Their Anthocyanin and Fiber Fractions Alter the Composition and Diversity of Gut Microbiota in F-344 Rats

“…Decreased levels of Akkermansia have been observed in patients with inflammatory bowel diseases, such as ulcerative colitis, and metabolic disorders, such as obesity and diabetes, suggesting its potential anti-inflammatory effects (39). Supplementation of Akkermansia (40) or feeding certain natural compounds that can increase the abundance of Akkermansia , such as red pitaya ( Hylocereus polyrhizus ) betacyanins (41), could attenuate the inflammation in mice, suggesting an anti-inflammatory role of Akkermansia . In addition, decreased abundance of Desulfovibrio has been reported in the high-fat diet-induced obese mice, which were associated with elevated inflammation and the activation of the Wnt pathway (42).…”

Introduction to the human gut microbiota

“…The protective role of A. muciniphila could be recapitulated using A. muciniphila purified membrane protein or the pasteurised bacterium [86]. Recently, A. muciniphila supplementation was shown to significantly alleviate body weight gain and reduce fat mass in chow diet-fed mice by relieving metabolic inflammation [87]. These studies suggest the potential of A. muciniphila as a therapeutic option to target human obesity and associated disorders.…”

“…Colonisation with SFB may also direct post-natal maturation of the gut mucosal lymphoid tissue, trigger a potent and broad IgA response, stimulate the T-cell compartment and up-regulate intestinal innate defence mediators, suggesting immune-stimulatory capacities of SFB (as reviewed in [143]). A. muciniphila has been correlated with protection against several inflammatory diseases [84,87,166–170], suggesting that this strain possesses anti-inflammatory properties although the underlying mechanisms have not been completely elucidated [171]. Individuals with CD display mucosal dysbiosis characterised by reduced diversity of core microbiota and lower abundance of F. prausnitzii [172].…”

Function of Akkermansia muciniphila in Obesity: Interactions With Lipid Metabolism, Immune Response and Gut Systems

“…Diets rich in prebiotic fiber increased the number of A. muciniphila in the microbiome (Gomez-Gallego et al, 2016). Meanwhile, direct probiotic supplements can cause a >100-fold enrichment in the level of A. muciniphila (Everard et al, 2013;Zhao et al, 2017). Pomegranate extract promoted the growth of A. muciniphila in vivo and led to the formation of ellagic acid Henning et al, 2017).…”