{"id":1005,"date":"2016-03-18T11:00:51","date_gmt":"2016-03-18T11:00:51","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=1005"},"modified":"2017-08-21T11:03:40","modified_gmt":"2017-08-21T11:03:40","slug":"primary-care-corner-with-geoffrey-modest-md-microbiome-changes-and-severity-of-nafld","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/03\/18\/primary-care-corner-with-geoffrey-modest-md-microbiome-changes-and-severity-of-nafld\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Microbiome Changes and Severity of NAFLD"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>There is not a great understanding as to which patients with\u00a0non-alcoholic fatty liver disease (NAFLD), the most common liver disorder\u00a0in the US\/Western countries, are among the\u00a020-30% who progress to\u00a0nonalcoholic steatohepatitis (NASH), or those who progress even further to fibrosis and cirrhosis. Certain genetic polymorphisms have been identified which predispose people to more aggressive disease: there are some data that\u00a0the I148M variant of the\u00a0PNPLA3 gene confers a 3.5-fold increased risk of NASH and a 3.2-fold increased risk of fibrosis. And there may be roles for epigentics, gender\/hormone status, and nutrition as well. This article looked at the potential role of the gut microbiome (see HEPATOLOGY 2016;63:764), since as noted in several blogs (see below), there may also be a role of microbiome changes in some related conditions (e.g.,\u00a0obesity, metabolic syndrome, diabetes).<\/p>\n<p>Details:<\/p>\n<ul>\n<li>30 patients with no\/only periportal F0\/F1 fibrosis (10 with\u00a0NASH) and 27 patients with significant F\u22652\u00a0fibrosis (25 with NASH) had 16S ribosomal RNA gene sequencing of stool samples. All patients had liver biopsy diagnosis, did not drink alcohol\u00a0&gt;210 g\/week for men or &gt;140 g\/week for women, did not have chronic hepatitis B or C, and did not have evidence of other chronic liver diseases on biopsy.<\/li>\n<li>Mean age 57, 34 males\/23 females, BMI 31, 40% with diabetes, 50% elevated triglycerides, 75%\u00a0depressed HDL, 81% with metabolic syndrome, mean AST of 40 and ALT of 64.<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li>Bacteroides\u00a0was significantly more abundant in those with NASH and\u00a0F\u22652\u00a0fibrosis;\u00a0Prevotella was decreased (these two genera are competitors\u00a0with\u00a0an inverse abundance relationship). Also,\u00a0Ruminococcus\u00a0 was increased.<\/li>\n<li>On multivariate analysis (adjusting for BMI, BP, triglycerides, HDL, metabolic syndrome), Bacteroides was independently associated with NASH, and Ruminococcus with\u00a0F\u22652\u00a0fibrosis.<\/li>\n<li>\u200bThere was a dose-response curve: both the rate of NASH and F\u22652\u00a0fibrosis tracked with increasing abundance of Bacteroides and Ruminococcus, respectively<\/li>\n<li>\u200bIn the subgroup with metabolic syndrome (overall a group with\u00a0higher risk of more severe NAFLD lesions), those with more abundant Bacteroides and Ruminococcus had more severe NAFLD lesions. This was also found in those with diabetes and several of the components of metabolic syndrome<\/li>\n<li>In assessing the presumed functional effects of these bacterial changes, those with NASH had a microbiome enriched in ability to metabolize carbohydrates, lipids, and\u00a0amino acids.<\/li>\n<li>This study adds to the potential role of microbiome changes in causing clinical diseases. The study itself cannot imply causality, just an association: for example,\u00a0did the microbiome cause\u00a0the changes in the microbiome, or vs vice versa? Were there other nonetiologic\u00a0factors that caused both the microbiome changes in these patients\u00a0and\u00a0the NAFLD\/NASH\u00a0changes in the liver,such as eating too much p\u00e2t\u00e9 (this was a French study, after all)? But, arguments in favor of the microbiome changes being causal:\n<ul>\n<li>Animal studies\u00a0show that manipulating the gut microbiome can lead to changes in the liver lesions of NAFLD, including steatosis, NASH, fibrosis and liver cancer<\/li>\n<li>\u200bBacteroides is associated with increased fecal content of\u00a0deoxycholic acid, D-pinitol, choline, farrrinose, and stachyose (the last 2 containing glucose and fructose), and lower amounts of short-chain fatty acids (SFCAs)\u00a0and amino acids. And deoxycholic acid induces\u00a0apoptosis in the rat liver and is increased in NASH patients, fructose is associated with increased liver inflammation and fibrosis in NAFLD patients, and decreased SCFAs (esp. butyrate, propionate and acetate &#8212;\u00a0see Curr Opin Clin Nutr Metab Care 2014, 17:139)\u00a0may be detrimental to NAFLD<\/li>\n<li>Bacteroides is favored overall in the gut when people eat western diets (high in fat, animal proteins, and sugar), vs Prevotella being favored in those eating foods rich in fiber, starch and plant polysaccharides. In fact changing the diet to an animal-based one leads to a rapid shift in the gut microbiome to Bacteroides, and promotes insulin resistance.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>So, what are the implications of this study:<\/p>\n<ul>\n<li>This study and others on the microbiome (for example, see blogs: <a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/microbiome\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/microbiome\/<\/a>\u200b\u00a0) reinforce that there seems to be\u00a0a dynamic interrelationship between the gut microbiome and human disease, and that the changes in the microbiome lead to changes in bacterial metabolism and byproducts, which may be the mediators\/abettors of disease processes.<\/li>\n<li>There are several key players affecting the composition of the gut microbiome, including diet [see above microbiome blogs for articles on red meat and heart disease, medications (including one on metformin suggesting that much of its hypoglycemic role is as a promoter of healthy changes in the microbiome) as well as\u00a0on antibiotics, and exercise]<\/li>\n<li>And, I think that the associations with NAFLD above (even if not clearly causal) will expand my approach to patients with NAFLD\u00a0to include reinforcing a vegetable-based diet, as well as my usual approach of weight loss, lipid control, and exercise.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Microbiome Changes and Severity of NAFLD [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2016\/03\/18\/primary-care-corner-with-geoffrey-modest-md-microbiome-changes-and-severity-of-nafld\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":148,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[14283],"tags":[],"class_list":["post-1005","post","type-post","status-publish","format-standard","hentry","category-archive"],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1005","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/users\/148"}],"replies":[{"embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/comments?post=1005"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/1005\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=1005"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=1005"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=1005"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}