An in vitro medium for modeling gut dysbiosis associated with cystic fibrosis.

The gut physiology of pediatric and adult persons with cystic fibrosis (pwCF) is altered relative to healthy persons. The CF gut is characterized, in part, as having excess mucus, increased fat content, acidic pH, increased inflammation, increased antibiotic perturbation, and the potential for increased oxygen availability. These physiological differences shift nutritional availability and the local environment for intestinal microbes, thus likely driving significant changes in microbial metabolism, colonization, and competition with other microbes. The impact of any specific change in this physiological landscape is difficult to parse using human or animal studies. Thus, we have developed a novel culture medium representative of the CF gut environment, inclusive of all the aforementioned features. This medium, called CF-MiPro, maintains CF gut microbiome communities, while significantly shifting nonCF gut microbiome communities toward a CF-like microbial profile, characterized by low Bacteroidetes and high Proteobacteria abundance. This medium is able to maintain this culture composition for up to 5 days of passage. Additionally, microbial communities passaged in CF-MiPro produce significantly less immunomodulatory short-chain fatty acids (SCFA), including propionate and butyrate, than communities passaged in MiPro, a culture medium representative of healthy gut physiology, confirming not only a shift in microbial composition but also altered community function. Our results support the potential for this in vitro culture medium as a new tool for the study of CF gut dysbiosis. IMPORTANCE Cystic fibrosis is an autosomal recessive disease that disrupts ion transport at mucosal surfaces, leading to mucus accumulation and altered physiology of both the lungs and the intestines, among other organs, with the resulting altered environment contributing to an imbalance of microbial communities. Culture media representative of the CF airway have been developed and validated; however, no such medium exists for modeling the CF intestine. Here, we develop and validate a first-generation culture medium inclusive of features that are altered in the CF colon. Our findings suggest this novel medium, called CF-MiPro, as a maintenance medium for CF gut microbiome samples and a flexible tool for studying key drivers of CF-associated gut dysbiosis.

An In Vitro Medium for Modeling Gut Dysbiosis Associated with Cystic Fibrosis.

The gut physiology of pediatric and adult persons with cystic fibrosis (pwCF) is altered relative to healthy persons. The CF gut is characterized, in part, as having excess mucus, increased fat content, acidic pH, increased inflammation, increased antibiotic perturbation and the potential for increased oxygen availability. These physiological differences shift nutritional availability and the local environment for intestinal microbes, thus likely driving significant changes in microbial metabolism, colonization and competition with other microbes. The impact of any specific change in this physiological landscape is difficult to parse using human or animal studies. Thus, we have developed a novel culture medium representative of the CF gut environment, inclusive of all the aforementioned features. This medium, called CF-MiPro, maintains CF gut microbiome communities, while significantly shifting non-CF gut microbiome communities toward a CF-like microbial profile, characterized by low Bacteroidetes and high Proteobacteria abundance. This medium is able to maintain this culture composition for up to 5 days of passage. Additionally, microbial communities passaged in CF-MiPro produce significantly less immunomodulatory short chain fatty acids (SCFA), including propionate and butyrate, than communities passaged in MiPro, a culture medium representative of healthy gut physiology, confirming not only a shift in microbial composition but altered community function. Our results support the potential for this in vitro culture medium as a new tool for the study of gut dysbiosis in CF.

Use of proton pump inhibitors is associated with lower hemoglobin levels in people with cystic fibrosis.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine H2-receptor antagonists (H2RAs) are commonly prescribed to people with cystic fibrosis (PwCF) to treat gastroesophageal reflux disease (GERD) and/or protect pancreatic enzymes from degradation in the stomach. Acid suppressive medications (ASMs) could theoretically reduce hemoglobin (Hgb) levels by restricting enteral iron absorption, but evidence of an association between use of ASMs and lower Hgb levels is lacking in PwCF. METHODS: We used unadjusted and covariate-adjusted generalized linear mixed models (GLMMs) to estimate the fixed effects of using versus never using ASMs on annual Hgb levels of PwCF in the U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) from 2011 to 2017. RESULTS: There were 9850 users and 9007 never-users of ASMs from 2011 to 2017 who met inclusion criteria. Not adjusting for covariates, Hgb estimates were lower for male and female H2RA and/or PPI users versus never-users. Adjusting for covariates, mean Hgb was 0.1 g/dl (95% CI: 0.03, 0.17) lower for males that exclusively used PPIs than it was for male never-users of ASMs (p = .008). Adjusting for covariates, mean Hgb levels were 0.11 g/dl (95% CI: 0.04, 0.18) lower for females that exclusively used PPIs and 0.16 g/dl (95% CI: 0.05, 0.27) lower for females that used PPIs and H2RAs concurrently than it was for female never-users of ASMs (p = .005 and p = .002 for respective comparisons). CONCLUSIONS: Males and females with cystic fibrosis (CF) who used PPIs and females with CF who concurrently used PPIs and H2RAs had lower Hgb levels than never-users of ASMs of the same sex in the CFFPR from 2011 to 2017.