Cystic fibrosis transmembrane conductance regulator modulates enteric cholinergic activities and is abnormally expressed in the enteric ganglia of patients with slow transit constipation

Yeh, Ka Ming; Johansson, Ӧlle; Le, Huy; Rao, K. A.; Markus, Irit; Perera, Dayashan Shevy; Lubowski, David Z.; King, D. W.; Zhang, Li; Chen, Hongzhuan; Liu, Lu

doi:10.1007/s00535-019-01610-9

Cited by 16 publications

(12 citation statements)

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“…CFTR is found in the human central and enteric nervous systems, especially myenteric ganglia, and may be modulated by enteric cholinergic neurotransmitters [ 30 , 31 ]. Yeh et al found downregulated CFTR and choline acetyltransferase in myenteric ganglia of slow transit human colon compared to control [32] . The literature on human studies of CFTR in the GI muscle and nervous system is limited compared to animal (mouse and piglet) studies, yet these observations in animals pave the path for new research to delineate causes of dysmotility in CF [ 26 , 27 , 30 , 32 , 33 ].…”

Section: Pathophysiology Of Cf-related Gut Dysfunctionmentioning

confidence: 98%

Review of Gastrointestinal Motility in Cystic Fibrosis

Henen

Denton

Teckman

et al. 2021

Journal of Cystic Fibrosis

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Gastrointestinal manifestations in patients with cystic fibrosis (CF) are extremely common and have recently become a research focus. Gastrointestinal (GI) dysfunction is poorly understood in the CF population, despite many speculations including the role of luminal pH, bacterial overgrowth, and abnormal microbiome. Nevertheless, dysmotility is emerging as a possible key player in CF intestinal symptoms. Our review article aims to explore the sequelae of defective cystic fibrosis transmembrane conductance regulator (CFTR) genes on the GI tract as studied in both animals and humans, describe various presentations of intestinal dysmotility in CF, review newer diagnostic motility techniques including intraluminal manometry, and review the current literature regarding the potential role of dysmotility in CF-related intestinal pathologies.

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Section: Pathophysiology Of Cf-related Gut Dysfunctionmentioning

confidence: 98%

Review of Gastrointestinal Motility in Cystic Fibrosis

Henen

Denton

Teckman

et al. 2021

Journal of Cystic Fibrosis

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“…Evidence has also emerged to indicate that CFTR may have critical functions beyond ion transport. It has been demonstrated that CFTR is present in myenteric ganglia and may modulate enteric neurotransmission by mediating acetylcholine release, thereby regulating gut motility [75,76]. As such, dysmotility in CF and subsequent inflammation may, in part, be due to an aberrant enteric nervous system; however, this hypothesis has not yet been extensively explored.…”

Section: Intestinal Dysmotilitymentioning

confidence: 99%

Intestinal Inflammation and Alterations in the Gut Microbiota in Cystic Fibrosis: A Review of the Current Evidence, Pathophysiology and Future Directions

Tam

Dorst

McKay

et al. 2022

JCM

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Cystic fibrosis (CF) is a life-limiting autosomal recessive multisystem disease. While its burden of morbidity and mortality is classically associated with pulmonary disease, CF also profoundly affects the gastrointestinal (GI) tract. Chronic low-grade inflammation and alterations to the gut microbiota are hallmarks of the CF intestine. The etiology of these manifestations is likely multifactorial, resulting from cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction, a high-fat CF diet, and the use of antibiotics. There may also be a bidirectional pathophysiological link between intestinal inflammation and changes to the gut microbiome. Additionally, a growing body of evidence suggests that these GI manifestations may have significant clinical associations with growth and nutrition, quality of life, and respiratory function in CF. As such, the potential utility of GI therapies and long-term GI outcomes are areas of interest in CF. Further research involving microbial modulation and multi-omics techniques may reveal novel insights. This article provides an overview of the current evidence, pathophysiology, and future research and therapeutic considerations pertaining to intestinal inflammation and alterations in the gut microbiota in CF.

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“…ACh released by cholinergic nerves is the most important excitatory neurotransmitter in the gastrointestinal tract (Yeh et al 2019). ACh binds to muscarinic receptor 3 (M3) to mediate the contraction of gastrointestinal smooth muscle.…”

Section: Effects Of Anwulignan On the Content Of Ach The Activity Of Chat And The Expression Of M3 In The Jejunal Tissuementioning

confidence: 99%

“…ACh binds to muscarinic receptor 3 (M3) to mediate the contraction of gastrointestinal smooth muscle. ChAT (choline acetyltransferase) is an important catalytic enzyme in the synthesis of ACh, and its activity is positively correlated with the level of ACh (Yeh et al 2019). The experimental results (Figure 6) showed that compared with those in Sham group, the content of ACh, the activity of ChAT and the expression of M3 protein in the jejunal tissue of rats were significantly decreased in II/R group (P < 0.01); but all of them were significantly increased in II/R+Anwu group (P < 0.01) compared with those in II/R group, indicating that anwulignan could protect the contractile function of jejunal smooth muscle by increasing the ACh content, ChAT activity and M3 protin expression in the jejunal tissue of II/R rats.…”

Section: Effects Of Anwulignan On the Content Of Ach The Activity Of Chat And The Expression Of M3 In The Jejunal Tissuementioning

confidence: 99%