Bacterial overgrowth, dysbiosis, inflammation, and dysmotility in the Cystic Fibrosis intestine

Dorsey, Jill; Gonska, Tanja

doi:10.1016/j.jcf.2017.07.014

Cited by 94 publications

(93 citation statements)

References 68 publications

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“…While a great deal of attention has been focused on therapies to treat the chronic airway infections that are often the proximal cause of mortality, it is the gastrointestinal complications that are the cause of significant morbidity for CF patients in early life (7)(8)(9)(10). Infants and young children with CF experience difficulty with absorbing nutrients secondary to meconium ileus, pancreatic insufficiency, and small bowel bacterial overgrowth (9,(11)(12)(13). Poor weight gain is common, resulting in the need for a high-calorie diet beginning early in life and treatment with pancreatic enzyme replacement therapy (14).…”

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confidence: 99%

Altered Stool Microbiota of Infants with Cystic Fibrosis Shows a Reduction in Genera Associated with Immune Programming from Birth

et al. 2019

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Previous work from our group indicated an association between the gastrointestinal microbiota of infants with cystic fibrosis (CF) and airway disease in this population. Here we report that stool microbiota of infants with CF demonstrates an altered but largely unchanging within-individual bacterial diversity (alpha diversity) over the first year of life, in contrast to the infants without CF (control cohort), which showed the expected increase in alpha diversity over the first year. The beta diversity, or between-sample diversity, of these two cohorts was significantly different over the first year of life and was statistically significantly associated with airway exacerbations, confirming our earlier findings. Compared with control infants, infants with CF had reduced levels of Bacteroides, a bacterial genus associated with immune modulation, as early as 6 weeks of life, and this significant reduction of Bacteroides spp. in the cohort with CF persisted over the entire first year of life. Only two other genera were significantly different across the first year of life: Roseburia was significantly reduced and Veillonella was significantly increased. Other genera showed differences between the two cohorts but only at selected time points. In vitro studies demonstrated that exposure of the apical face of polarized intestinal cell lines to Bacteroides species supernatants significantly reduced production of interleukin 8 (IL-8), suggesting a mechanism whereby changes in the intestinal microbiota could impact inflammation in CF. This work further establishes an association between gastrointestinal microbiota, inflammation, and airway disease in infants with CF and presents a potential opportunity for therapeutic interventions beginning in early life. IMPORTANCE There is growing evidence for a link between gastrointestinal bacterial communities and airway disease progression in CF. We demonstrate that infants with CF ≤1 year of age show a distinct stool microbiota versus that of control infants of a comparable age. We detected associations between the gut microbiome and airway exacerbation events in the cohort of infants with CF, and in vitro studies provided one possible mechanism for this observation. These data clarify that current therapeutics do not establish in infants with CF a gastrointestinal microbiota like that in healthy infants, and we suggest that interventions that direct the gastrointestinal microbiota closer to a healthy state may provide systemic benefits to these patients during a critical window of immune programming that might have implications for lifelong health.

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confidence: 99%

Altered Stool Microbiota of Infants with Cystic Fibrosis Shows a Reduction in Genera Associated with Immune Programming from Birth

et al. 2019

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“…The mucus layer, especially in the small bowel, is thick and adherent, contributing to problems with small bowel overgrowth, a change in the microbiome, gut inflammation, and dysmotility. 27 Gut microbiome changes are implicated in inflammatory arthritides including rheumatoid and spondyloarthropathies. Some of these changes may be driven by changes in T-cell differentiation associated with dysbiosis.…”

Section: Possible Pathogenesis Of Cfamentioning

confidence: 99%

Assessing arthritis in the context of cystic fibrosis

Clarke

Watson

Freeston

et al. 2019

Pediatric Pulmonology

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Inflammatory arthritis in the context of cystic fibrosis (CF) can represent a diagnostic and therapeutic challenge. Poor recognition and under‐treatment of musculoskeletal conditions increases symptom burden, affects quality of life, and may lead to changes to an individual's ability to carry out activities of daily living and to exercise. A careful assessment and multidisciplinary approach is essential when considering a diagnosis of CF‐associated arthritis (CFA), both in terms of identifying other treatable conditions, such as rheumatoid arthritis, and effectively addressing symptoms. In this collaboration between CF specialists and Rheumatologists, we consider joint symptoms in patients with CF, with a focus on CFA. We offer a differential diagnosis list and consider steps to assess and manage CF patients presenting with arthralgia including appropriate up‐to‐date rheumatological assessment.

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“…19 Laboratory findings associated with SIBO are related to nutrient malabsorption and may include deficiencies of fat-soluble vitamins, vitamin B12, and/or iron. 22,23 The gold standard for diagnosis of SIBO is the direct aspiration and culture of duodenal fluid; however, this is an invasive approach, and may underestimate bacterial burden in patients with CF due to increased concentration of bacteria in the adherent mucus layer. 23,24 Breath testing is a noninvasive testing modality that measures exhaled hydrogen or methane produced by bacterial fermentation after ingestion of a lactulose or glucose load.…”

Section: Testmentioning

confidence: 99%

“…22,23 The gold standard for diagnosis of SIBO is the direct aspiration and culture of duodenal fluid; however, this is an invasive approach, and may underestimate bacterial burden in patients with CF due to increased concentration of bacteria in the adherent mucus layer. 23,24 Breath testing is a noninvasive testing modality that measures exhaled hydrogen or methane produced by bacterial fermentation after ingestion of a lactulose or glucose load. The inclusion of the methane measurement is of particular importance as individuals with CF are more likely to not produce hydrogen from lactulose than non-CF patients.…”

Section: Testmentioning

confidence: 99%

Gastrointestinal and Hepatobiliary Disease in Cystic Fibrosis

Gabel

Galante

Freedman

2019

Semin Respir Crit Care Med

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Cystic fibrosis (CF) is a multiorgan disease, and gastrointestinal (GI) manifestations can contribute to significant morbidity and mortality for individuals with CF. Up to 85% of patients with CF experience GI symptoms, thus addressing the GI aspects of this disease is paramount. With the advent of highly effective CF transmembrane conductance regulator modulators that are increasingly available, many individuals with CF now have significantly improved life expectancy. With these advances, GI manifestations that can be a detriment to quality of life such as gastroesophageal reflux disease, dysbiosis, and chronic abdominal pain have become a priority for patients and caregivers. In addition, as individuals have increased longevity, it has become essential for care providers to be aware of topics such as hepatobiliary disease and colorectal cancer screening. An understanding of the wide scope of GI manifestations in CF can enable providers to optimize the overall health and well-being of their patients. In this review, we aim to provide an up-to-date overview of key aspects of GI and hepatic disease in CF.

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Bacterial overgrowth, dysbiosis, inflammation, and dysmotility in the Cystic Fibrosis intestine

Cited by 94 publications

References 68 publications

Altered Stool Microbiota of Infants with Cystic Fibrosis Shows a Reduction in Genera Associated with Immune Programming from Birth

Altered Stool Microbiota of Infants with Cystic Fibrosis Shows a Reduction in Genera Associated with Immune Programming from Birth

Assessing arthritis in the context of cystic fibrosis

Gastrointestinal and Hepatobiliary Disease in Cystic Fibrosis

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