Modulation of gut microbiota mediates berberine‐induced expansion of immuno‐suppressive cells to against alcoholic liver disease

Abstract

Background Berberine is an isoquinoline alkaloid compound derived from many herbs, which has been used extensively to improve liver function. But action mechanism of its hepatoprotection in alcoholic liver disease (ALD) is far from being clear. Aim To investigate the underlying mechanism of berberine's therapeutic effect on ALD associated with gut microbiota‐immune system axis. Method An animal model fed with ethanol that mimics drinking pattern ideally in ALD patients was established. Liver function was evaluated by biochemical test and histological examination. Immune cells were detected by flow cytometry and feces samples were collected for 16S rRNA gene amplicon sequencing. Results We first reported the promising beneficial effect of berberine on ameliorating acute‐on‐chronic alcoholic hepatic damage and explored the underlying mechanism involving gut microbiota‐immune system axis. Notably, berberine activated a population with immune suppressive function, defined as granulocytic‐ myeloid‐derived suppressor cell (G‐MDSC)‐like population, in the liver of mice with alleviating alcohol‐induced hepatic injury. Berberine remarkably enhanced the increase of G‐MDSC‐like cells in blood and liver and decreased cytotoxic T cells correspondingly. Suppression of G‐MDSC‐like population significantly attenuated the protective effect of berberine against alcohol. Berberine activated IL6/STAT3 signaling in in vitro culture of G‐MSDCs‐like population, while inhibition of STAT3 activity attenuated the activation of this population by berberine. Moreover, berberine changed the overall gut microbial community, primarily increased the abundance of Akkermansia muciniphila. Of note, depletion of gut microbiota abolished the inducing effect of berberine on G‐MDSC‐like population, and attenuated its hepatoprotective effect against alcohol in mice, suggesting intestinal flora might be involved in mediating the expansion of this protective population. Conclusion Collectively, this study delivered insight into the role of immunosuppressive response in ALD, and facilitated the understanding of the pharmacological effects and action mechanisms of berberine.

Prebiotic Effect of Berberine and Curcumin Is Associated with the Improvement of Obesity in Mice

“…level. In addition, an important increase in Akkermansia was only observed after berberine intake, in line with other studies showing berberine’s impact on this interesting bacterium [ 45 , 46 , 47 , 49 ]. The limitation is that we cannot exclude that other bacteria than the ones measured have been affected by the dietary treatments and may contribute to the effects demonstrated in the present study.…”

“…Other bacteria belonging to Lachnospiraceae and Desulfovibrionaceae may also decrease upon berberine treatment in diabetic mice [ 45 ]. Furthermore, the abundance of Terrisporobacter and Helicobacter has been shown to increase while that of Pseudoflavonifractor, Mucisirillum, Alistipes, Ruminiclostridium and Lachnoclostridium decreased after berberine treatment in an animal model of alcoholic liver disease, even if A. muciniphila was the one that was most remarkably influenced by berberine administration [ 49 ]. By which mechanisms would berberine intake affect the composition of the gut microbiota?…”

Protective Mechanism of Edible Food Plants against Alcoholic Liver Disease with Special Mention to Polyphenolic Compounds

“…Additionally, it was also reported that BBR changes the overall gut microbial composition, mainly by increasing the abundance of Akkermansia muciniphila . Collectively, their results reveal that BBR attenuates ALD by modulating the gut microbiota and immunosuppressive response in ALD [ 115 ].…”

The Relationship between Hepatic Myeloid-Derived Suppressor Cells and Clinicopathological Parameters in Patients with Chronic Liver Disease

“…As one of the important compo-nents of the immunosuppressive network, MDSCs have been shown to facilitate tumor formation by blocking the host immune system [6]. Recent studies support the role of MDSCs as essential regulators of chronic inflammatory liver diseases, and MDSCs are expanded in pathological conditions such as malignancy or infection and suppress antitumor immunity [10], and the liver is an important site of MDSC induction for extrahepatic infections and cancer [20][21][22]. The expression of CD33 and CD11b on activated monocytes and macrophages was associated with the disease progression and poor survival of patients [23].…”