Robustness of the non-neuronal cholinergic system in rat large intestine against luminal challenges
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Acetylcholine and atypical esters of choline such as propionyl- and butyrylcholine are produced by the colonic epithelium and are released when epithelial receptors for short-chain fatty acids (SCFA) are stimulated by propionate. It is assumed that the SCFA used by the choline acetyltransferase (ChAT), the central enzyme for the production of these choline esters, originate from the colonic lumen, where they are synthesized during the bacterial fermentation of carbohydrates. Therefore, it seemed to be of interest to study whether the non-neuronal cholinergic system in the colonic epithelium is affected by maneuvers intended to stimulate or to inhibit colonic fermentation by changing the intestinal microbiota. In two series of experiments, rats were either fed with a high fiber diet (15.5% (w/v) crude fibers in comparison to 4.6% (w/w) in the control diet) or treated orally with the antibiotic vancomycin. High fiber diet induced an unexpected decrease in the luminal concentration of SCFA in the colon, but an increase in the caecum, suggesting an upregulation of colonic SCFA absorption, whereas vancomycin treatment resulted in the expected strong reduction of SCFA concentration in colon and caecum. MALDI MS analysis revealed a decrease in the colonic content of propionylcholine by high fiber diet and by vancomycin. High fiber diet caused a significant downregulation of ChAT expression on protein and mRNA level. Despite a modest increase in tissue conductance during the high fiber diet, main barrier and transport properties of the epithelium such as basal short-circuit current (Isc), the flux of the paracellularly transported marker, fluorescein, or the Isc induced by epithelial acetylcholine release evoked by propionate remained unaltered. These results suggest a remarkable stability of the non-neuronal cholinergic system in colonic epithelium against changes in the luminal environment underlying its biological importance for intestinal homeostasis.
KeywordsAcetylcholine Antibiotics Caecum Colon Epithelium Rat Short-chain fatty acids
The diligent technical assistance of Mrs. Marion Burmester, Brigitta Buss, Bärbel Schmidt, and Alice Stockinger is a pleasure to acknowledge. Financial support by the Deutsche Forschungsgemeinschaft (DFG) under project Sp314/13-1 is gratefully acknowledged.
- 4.Argenzio RA, Southworth M (1974) Sites of organic acid production and absorption in gastrointestinal tract of the pig. Am J Phys 228:454–460Google Scholar
- 5.Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Ap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen HM, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, De Vos WM, Brunak S, Doré J, MetaHIT Consortium, Weissenbach J, Ehrlich S, Bork P (2011) Enterotypes of the human gut microbiota. Nature 473:174–180CrossRefGoogle Scholar
- 11.Breves G, Gädeken D (1988) Volumen und Retentionszeit der partikelfreien Flüssigkeit im Dickdarm von wachsenden Schweinen. Landbauforsch Völkenrode 38:349–352Google Scholar
- 12.Bugaut M (1987) Occurence, absorption and metabolism of short chain fatty acids in the digestive tract of mammals. Comp Biochem Physiol 86B:439–472Google Scholar
- 17.Farrell DJ, Johnson KA (1972) Utilization of cellulose by pigs and its effects on caecal function. Anim Sci 14:209–217Google Scholar
- 30.Schemann M, Sann H, Schaaf C, Mäder M (1993) Identification of cholinergic neurons in enteric nervous system by antibodies against choline acetyltransferase. Am J Phys 265:G1005–G1009Google Scholar
- 39.Yajima M, Kimura S, Karaki S, Nio-Kobayashi J, Tsuruta T, Kuwahara A, Yajima T, Iwanaga T (2016) Non-neuronal, but atropine-sensitive ileal contractile responses to short-chain fatty acids: age-dependent desensitization and restoration under inflammatory conditions in mice. Phys Rep 4:e12759CrossRefGoogle Scholar