{"id":916,"date":"2015-12-10T15:24:11","date_gmt":"2015-12-10T15:24:11","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=916"},"modified":"2017-08-21T11:17:04","modified_gmt":"2017-08-21T11:17:04","slug":"primary-care-corner-with-geoffrey-modest-md-troubling-microbiome-changes","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/12\/10\/primary-care-corner-with-geoffrey-modest-md-troubling-microbiome-changes\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Troubling Microbiome Changes"},"content":{"rendered":"<p><strong>By Dr. Geoffrey Modest<\/strong><\/p>\n<p>A couple of recent studies have found very troubling microbial changes, one dealing with the effect of PPIs on the gut microbiome, the other with the evolution of a very serious development in antibiotic resistance.<\/p>\n<p>I sent out a blog in\u00a0December 2014 on use of PPIs (proton-pump inhibitors) and changes in the microbiome (see\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2014\/12\/03\/primary-care-corner-with-geoffrey-modest-md-gastric-acid-suppression-and-the-microbiome\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2014\/12\/03\/primary-care-corner-with-geoffrey-modest-md-gastric-acid-suppression-and-the-microbiome\/<\/a> ), which noted that gastric acid suppression (mostly with PPIs)\u00a0in kids led to pretty profound changes in both the lung and gut microbiomes. Another study just came out looking at the PPI-associated\u00a0gut microbiome changes\u00a0in adults, which could predispose people to C. difficile infections (see\u00a0Gastroenterology 2015;149:883).<\/p>\n<p>Details:<\/p>\n<ul>\n<li>Background: C diff infections happen more often in those on PPIs. There are data showing that increases in gut\u00a0Enterococcaceae and Streptococcaceae\u00a0and decreases in\u00a0Clostridiales taxa are associated with increased risk of subsequent\u00a0C diff infections in hospitalized patients, with infections related to later\u00a0use of NSAIDs and antibiotics, esp. cephalosporins or fluoroquinolones\u00a0(see J Infect Dis 2010; 202 (12): 1877). The relationship with NSAIDs is new to me, but there may be\u00a0direct effects on the microbiome perhaps through\u00a0decreased inflammatory response and increased proliferation of certain bad microbes including C diff.<\/li>\n<li>Open-label cross-over study of 12 healthy volunteers, none of whom had taken antibiotics in the past year or had baseline C diff in their stool\u00a0(small study, but the cross-over design adds more credibility, though no comment overall on the volunteers in terms of other meds, diet, exercise&#8230; all of which could affect the baseline microbiome)<\/li>\n<li>Assessed 2 baseline stool samples, 4\u00a0weeks apart, then volunteers\u00a0took omeprazole 40mg bid and collected stool sample at week 8. 6 subjects took the PPI for an additional 4 weeks and had another stool sample then checked at week 12.<\/li>\n<\/ul>\n<p>Results:<\/p>\n<ul>\n<li>No significant difference in the individual patients&#8217; gut microbiome diversity comparing baseline and on-medication samples<\/li>\n<li>But: there were differences in the actual taxa in the gut, which are associated with C difficile infections (Enterococcaceae and Streptococcaceae were increased, Clostridiales decreased), as well as taxa associated with GI bacterial overgrowth (increased Micrococcaceae and Staphylococcaceae)<\/li>\n<li>Functional analysis showed not changes in bile acids when on PPIs, but there was an increase in genes involved in bacterial invasion\u00a0(especially Staph aureus) and the renin-angiotensin system<\/li>\n<li>Not much difference in the\u00a0microbiome at 12 weeks in those who continued the\u00a0PPI\u00a0vs those\u00a0stopped\u00a0at week 8.<\/li>\n<\/ul>\n<p>So, as I mentioned in the 2014 blog, there are several infections that seem to be increased with PPI use:\u00a0 C diff, but also community-acquired pneumonia, and likely campylobacter and salmonella (as well as other non-infectious\u00a0problems, including malabsorption of magnesium, vit B12, iron, calcium&#8211; and some studies finding decreased bone density and increased fracture risk; and also\u00a0more atrophic gastritis, which may be a cancer precursor, esp. in those with concurrent H Pylori infections). The important issue here is that our medical interventions typically have wide-spread collateral\u00a0effects in the body, and for PPIs in particular, we should use them sparingly and step-down therapy to less potent agents as soon as we can do so clinically. \u00a0This small study, by finding a reasonable putative mechanism for C diff through adverse changes in the microbiome, further supports this approach.<\/p>\n<p>For other blogs on the microbiome, see:\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/microbiome\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/microbiome\/<\/a><\/p>\n<p>Another very, very concerning article hit the popular press regarding polymixin-resistance\u00a0likely related to use of antibiotics in meat production in China. This resistance\u00a0was transferred to humans through a plasmid\u00a0(see\u00a0doi.org\/10.1016\/S1473-3099(15)00424-7). China is the world&#8217;s largest producer of poulty and pig products\u00a0and one of the largest veterinary\u00a0users of colistin.<\/p>\n<p>Details:<\/p>\n<ul>\n<li>Background: prior polymixin resistance has involved chromosomal mutations. colistin (aka,\u00a0polymixin E) is an old antibiotic, but has not been used much because of the advent of aminoglycosides which have fewer\u00a0adverse effects. But, colistin is\u00a0now being used for panresistant infections such as Pseudomonas, Acinetobacter spp. and in carbapenem-producing Enterobacteriaceae. Until this study, colistin was not known to spread from cell-to-cell (e.g.,\u00a0as by a plasmid)<\/li>\n<li>On routine surveillance of animals, they found a pig with an\u00a0E coli strain with colistin resistance\u00a0which could be transferred to another strain through possible plasmid-mediated polymixin resistance<\/li>\n<li>Polymixin resistance could be transferred\u00a0in vivo to mice<\/li>\n<li>Plasmids were then found\u00a0in 78 of 523 samples of raw pig\u00a0meat (15%) and 166 of 804 pigs (21%) during 2011-14<\/li>\n<li>AND, <strong>they found plasmid-induced\u00a0colistin resistance\u00a0in 16 of 1322 samples from inpatients with infections<\/strong>!! (4 from urine, 3 from sputum, 3 from drainage fluid, 3 from ascitic fluid, 2 from bile and 1 from a wound)<\/li>\n<\/ul>\n<p>So, this is rather profound. We have lived in a prolonged era of effective\u00a0antibiotics, with the ability to treat almost all bacterial\u00a0infections and to keep up with the emergence of resistant strains. Much of the issue of antibiotic\u00a0resistance is attributable to the wanton and extensive veterinary\u00a0use of antibiotics. It seems that the little\u00a0microbes are pretty adept at keeping ahead of us, but unless we can stop both the excessive routine\u00a0veterinary use of antibiotics as well as our\u00a0overprescribing them (and their easy availability without prescription in many countries), it is unclear that we will be able to\u00a0continue to catch up with the\u00a0increasing resistance. In this Chinese\u00a0case, the prior mechanism of polymixin resistance (chromosomal changes) has evolved into a spreadable, plasmid-mediated one, and this is happening\u00a0in an antibiotic of last resort for some infections.<\/p>\n<p>See\u00a0<a href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/antimicrobial-resistance\/\">https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/category\/antimicrobial-resistance\/<\/a> for a large number of blogs on this, including the WHO report and a US White House report. \u00a0(i.e., there are lots of concerns around the world on this. at this point\u00a0the issue is not one of knowledge but one of action.)\u200b<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Primary Care Corner with Geoffrey Modest MD: Troubling Microbiome Changes [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/12\/10\/primary-care-corner-with-geoffrey-modest-md-troubling-microbiome-changes\/\">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-916","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\/916","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=916"}],"version-history":[{"count":0,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/posts\/916\/revisions"}],"wp:attachment":[{"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/media?parent=916"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/categories?post=916"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/wp-json\/wp\/v2\/tags?post=916"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}