The Intestinal Effect of Atorvastatin: Akkermansia muciniphila and Barrier Function

Abstract

Studies have shown that the cholesterol-lowering medicine statins alter the gut microbiome, induce chronic metabolic inflammation, and disrupt glycemic homeostasis. In this study, we aimed to investigate whether effects of atorvastatin (Ator) on gut microbiome and metabolic inflammation could be causally correlated. Mice at 8-week age were fed with high-fat diet (HFD) or HFD with Ator (HFD+Ator) for 16 weeks. 16S rRNA sequencing of stool and RNA sequencing of colon tissue were employed to analyze the intestinal alterations that could be induced by Ator. A human colon carcinoma cell line (Caco2) was used for in vitro experiments on barrier function. Compared to HFD, HFD+Ator induced more weight gain, impaired glucose tolerance, and led to gut microbiota dysbiosis, such as suppressing Akkermansia muciniphila in mice. The expressions of tight junction (TJ) proteins were attenuated in the colon, and the serum LPS-binding-protein (LBP) level was elevated in HFD+Ator mice, so as to transcriptionally activate the intestinal nuclear factor-k-gene binding (NF-κB) signaling pathway. Consistently, Ator impaired the barrier function of Caco2, and treatment of supernatant of A. Muciniphila culture could decrease the intestinal permeability and recover the attenuated expression of TJ proteins induced by Ator. In conclusion, long-term use of Ator with HFD may alter gut microbiota, induce intestinal barrier dysfunction, and hence promote chronic inflammation that contributes to disrupted glycemic homeostasis.

A thousand metagenome-assembled genomes of Akkermansia reveal phylogroups and geographical and functional variations in the human gut

“…Lv et al 10.3389/fcimb.2022.957439 In recent years, the geographic deviation among different subspecies has been described in several gut bacteria such as Prevotella copri (Tett et al, 2019) and Eubacterium rectale (Karcher et al, 2020). These findings suggested that not only the geographical factor but also other unknown factors (e.g., diet difference between populations (Cheng et al, 2021;Dıéz-Sainz et al, 2022), or movement of individuals) are probably the forces for speciation of the gut bacteria. Similarly, except for Amuc III, Amuc I, II, and IV were observed in the gut microbiota of American children in the study of Kirmiz et al (2020).…”

Fecal and Urinary Adipokines as Disease Biomarkers

“…Further complexity in the interpretation of urinary adipokine levels may arise from the fact that their serum concentrations can differ between sexes and are often related to BMI and metabolic diseases [ 2 , 21 , 48 , 50 , 151 , 165 , 226 ]. Commonly used drugs such as atorvastatin may promote intestinal barrier dysfunction and may also affect fecal and urinary protein levels [ 227 ]. However, how these parameters may influence urinary or fecal adipokine levels has not yet been thoroughly analyzed, and further research is required to clarify these issues.…”

Metabolome combined with gut microbiome revealed the lipid-lowering mechanism of Xuezhiping capsule on hyperlipidemic hamster induced by high fat diet

“…Studies have shown that long-term fed with high fat diet may alter gut microbiota, induce intestinal barrier dysfunction, and hence promote chronic inflammation that contributes to disrupted glycemic homeostasis ( He et al, 2020 ; Ahrens et al, 2021 ; Cheng et al, 2021 ). GP as one of the constituent drugs of XZP, reduced the Firmicutes/Bacteroidetes ratio ( Li S. et al, 2022 ), enriched the abundance of Lactococcus spp.…”