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

• Published in: PloS one Vol. 11; no. 11; p. e0166178
• Main Authors: Nadeem Aslam, Muhammad, Bassis, Christine M, Zhang, Li, Zaidi, Sameer, Varani, James, Bergin, Ingrid L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.11.2016; Public Library of Science (PLoS)
• Subjects: Acids; Akkermansia muciniphila; Amino acids; Animals; Bile; Bile Acids and Salts - metabolism; Biology and Life Sciences; Biomarkers - blood; Body weight; Calcium; Calcium (dietary); Calcium - pharmacology; Carbohydrates; Cecum; Cecum - microbiology; Cytokines - blood; Deoxycholic acid; Diet; Diet, High-Fat - adverse effects; Dietary supplements; Fatty liver; Feces - microbiology; Fibrosis; Gastrointestinal Microbiome - drug effects; High fat diet; House mouse; Hyperplasia; Injury prevention; Intestinal microflora; Laboratory animals; Liver; Liver - injuries; Liver - metabolism; Liver - pathology; Liver Cirrhosis - blood; Liver Cirrhosis - pathology; Liver diseases; Male; Medicine and Health Sciences; Metabolism; Mice; Mice, Inbred C57BL; Microbial activity; Microbiota; Microorganisms; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - pathology; Nutrient deficiency; Nutrition research; Obesity; Pathology; Research and Analysis Methods; Risk factors; Rodents; rRNA 16S; Steatosis; Studies; Weight control; Ann Arbor Michigan; United States > US; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0166178

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.