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1. Development of the intestinal microbiome in cystic fibrosis in early life

   https://doi.org/10.1128/msphere.00046-23  

   Price, Courtney E. ; Hampton, Thomas H. ; Valls, Rebecca A. ; Barrack, Kaitlyn E. ; O’Toole, George A. ; Madan, Juliette C. ; Coker, Modupe O. ( August 2023 , mSphere)

   Young, Vincent B. (Ed.)

   Cystic fibrosis is a heritable disease that disrupts ion transport at mucosal surfaces, causing a buildup of mucus and dysregulation of microbial communities in both the lungs and the intestines. Persons with CF are known to have dysbiotic gut microbial communities, but the development of these communities over time beginning at birth has not been thoroughly studied. Here, we describe an observation study following the development of the gut microbiome of cwCF throughout the first 4 years of life, during the critical window of both gut microbiome and immune development. Our findings indicate the possibility of the gut microbiota as a reservoir of airway pathogens and a surprisingly early indication of a microbiota associated with inflammatory bowel disease. 

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2. Cystic fibrosis transmembrane conductance regulator function, not TAS2R38 gene haplotypes, predict sinus surgery in children and young adults with cystic fibrosis

   https://doi.org/10.1002/alr.22548  

   Dalesio, Nicholas M. ; Aksit, Melis A. ; Ahn, Kwangmi ; Raraigh, Karen S. ; Collaco, Joseph M. ; McGrath‐Morrow, Sharon ; Zeitlin, Pamela L. ; An, Steven S. ; Cutting, Garry R. ( April 2020 , International Forum of Allergy & Rhinology)

   Chronic rhinosinusitis symptomatology begins in early childhood individuals with cystic fibrosis (CF). Cystic fibrosis transmembrane conductance regulator (CFTR) function contributes to sinus development and disease. Genetic variants of the bitter taste receptorTAS2R38have been suggested to contribute to sinus disease severity in individuals without CF. Our objective was to explore whether functionalTAS2R38haplotypes and CFTR function are associated with sinus disease or the need for sinus surgery in individuals with CF.

   We conducted a retrospective study using prospectively collected data from the CF Twin‐Sibling Study. The function of CFTR was assessed via chloride conductance. Genotyping of theTAS2R38gene identified patients who were homozygous for the functional haplotype, heterozygous, or homozygous for nonfunctional haplotypes. Clustered multivariate logistic regression was performed, controlling for sex and family relationship.

   A total of 1291 patients were evaluated. Patients with ≤1% CFTR function were 1.56 times more likely to require sinus surgery than those with >1% CFTR function (p= 0.049). CFTR function did not correlate significantly with the presence of sinus disease (p= 0.30). In addition, there were no statistically significant differences in diagnosis of sinus disease or need for sinus surgery between patients with functional and nonfunctionalTAS2R38haplotypes.

   CFTR function correlates with need for sinus surgery, whereasTAS2R38function does not appear to contribute to sinus disease or the need for sinus surgery in patients with CF.

    

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3. Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis

   https://doi.org/10.1126/scitranslmed.aav3488  

   Esther, Charles R. ; Muhlebach, Marianne S. ; Ehre, Camille ; Hill, David B. ; Wolfgang, Matthew C. ; Kesimer, Mehmet ; Ramsey, Kathryn A. ; Markovetz, Matthew R. ; Garbarine, Ian C. ; Forest, M. Gregory ; et al ( April 2019 , Science Translational Medicine)

   Although destructive airway disease is evident in young children with cystic fibrosis (CF), little is known about the nature of the early CF lung environment triggering the disease. To elucidate early CF pulmonary pathophysiology, we performed mucus, inflammation, metabolomic, and microbiome analyses on bronchoalveolar lavage fluid (BALF) from 46 preschool children with CF enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) program and 16 non-CF disease controls. Total airway mucins were elevated in CF compared to non-CF BALF irrespective of infection, and higher densities of mucus flakes containing mucin 5B and mucin 5AC were observed in samples from CF patients. Total mucins and mucus flakes correlated with inflammation, hypoxia, and oxidative stress. Many CF BALFs appeared sterile by culture and molecular analyses, whereas other samples exhibiting bacterial taxa associated with the oral cavity. Children without computed tomography–defined structural lung disease exhibited elevated BALF mucus flakes and neutrophils, but little/no bacterial infection. Although CF mucus flakes appeared “permanent” because they did not dissolve in dilute BALF matrix, they could be solubilized by a previously unidentified reducing agent (P2062), but not N -acetylcysteine or deoxyribonuclease. These findings indicate that early CF lung disease is characterized by an increased mucus burden and inflammatory markers without infection or structural lung disease and suggest that mucolytic and anti-inflammatory agents should be explored as preventive therapy. 

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4. Profiling the human intestinal environment under physiological conditions

   https://doi.org/10.1038/s41586-023-05989-7  

   Shalon, Dari ; Culver, Rebecca Neal ; Grembi, Jessica A. ; Folz, Jacob ; Treit, Peter V. ; Shi, Handuo ; Rosenberger, Florian A. ; Dethlefsen, Les ; Meng, Xiandong ; Yaffe, Eitan ; et al ( May 2023 , Nature)

   The spatiotemporal structure of the human microbiome^1,2, proteome³and metabolome^4,5reflects and determines regional intestinal physiology and may have implications for disease⁶. Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals⁷. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.

    

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5. Gut Microbiome: Profound Implications for Diet and Disease

   https://doi.org/10.3390/nu11071613  

   Hills, Ronald D. ; Pontefract, Benjamin A. ; Mishcon, Hillary R. ; Black, Cody A. ; Sutton, Steven C. ; Theberge, Cory R. ( July 2019 , Nutrients)

   The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease. 

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