Calcium Reduces Liver Injury in Mice on a High-Fat Diet: Alterations in Microbial and Bile Acid Profiles

Abstract

A high-fat “Western-style” diet (HFWD) promotes obesity-related conditions including non-alcoholic steatohepatitis (NASH), the histologic manifestation of non-alcoholic fatty liver disease (NAFLD). In addition to high saturated fat and processed carbohydrates, the typical HFWD is deficient in calcium. Calcium-deficiency is an independent risk factor for many conditions associated with the Western-style diet. However, calcium has not been widely evaluated in the context of NAFLD. The goal of the present study was to determine if dietary calcium supplementation could protect mice fed a HFWD from NAFLD, specifically by decreasing non-alcoholic steatohepatitis (NASH) and its down-stream consequences. Male C57BL/6NCrl mice were maintained for 18-months on a HFWD containing dietary calcium at either 0.41 gm/kg feed (unsupplemented) or 5.25 gm/kg feed (supplemented). Although there was no difference in body weight or steatosis, calcium-supplemented mice were protected against downstream consequences of hepatic steatosis, manifested by lower inflammation, less fibrosis, and by lower overall histologic NAFLD activity scores (NAS). Calcium supplementation correlated with distinctly segregating gut fecal and cecal microbial communities as defined by 16S rRNA gene sequence. Further, calcium supplementation also correlated with decreased hepatic concentration of the major conjugated murine primary bile acid, tauro-β-muricholic acid (as well as a decrease in the parent unconjugated bile acid). Thus, calcium was protective against progression of diet-induced hepatic steatosis to NASH and end-stage liver disease, suggesting that calcium supplementation may effectively protect against adverse hepatic consequences of HFWD in cases where overall diet modification cannot be sustained. This protective effect occurred in concert with calcium-mediated gut microbial community shifts and alterations of the hepatic bile acid pool.

The nasopharyngeal, ruminal, and vaginal microbiota and the core taxa shared across these microbiomes in virgin yearling heifers exposed to divergent in utero nutrition during their first trimester of gestation and in pregnant beef heifers in response to mineral supplementation

“…while reducing Bifidobacterium spp. in healthy men or mice (Nadeem Aslam et al, 2016; Trautvetter et al, 2018; Li et al, 2019). The impact of dietary supplementation with selenium, magnesium, iron or zinc on certain gut commensal or pathogenic microbes was also reported in children and mice (Yang et al, 2020).…”

Compositional alterations of gut microbiota in children with primary nephrotic syndrome after initial therapy

“…In addition, the medications of initial therapy in PNS included the compound of vitamin D3 and calcium carbonate. Lactococcus significantly enriched in adults treated with vitamin D3 for 12 weeks, and calcium supplementation could also increase the numbers of intestinal microbiota such as Ruminococcaceae,Akkermansia and Turicibacter [29, 30]. Therefore, the combination of prednisone, compound of Vitamin D3 and calcium carbonate might have a synergistic effect on gut microbiota in patients with PNS.…”

Qualitative and Quantitative Evaluation of Dietary Intake in Patients with Non-Alcoholic Steatohepatitis

“…Moreover, calcium seems to have a role in NASH pathogenesis and development: a 2016 research by Aslam et al showed that, in HFD diet-feed mice with calcium supplementation for 18 months, compared to only HFD diet mice, the first one had low inflammation and fibrosis, together with a reduced NAS score at histology. That was explained by its action on gut microbiota, that in calcium supplemented mice appeared to be colonized especially by Ruminococcaceae and Akkermansia, known to be associated with the so-called “healthy gut” for degrading polyglucans and for their action on lipid metabolism, but also by reducing total biliary acids pool (especially taurine-conjugated β-muricholic acid (MCA) and main murine biliary acid) that demonstrated to have citotossic capacity in NASH when present in high concentrations [ 72 ].…”