Introduction: The role of short-chain fatty acids (SCFAs) in colonic motility is controversial. Germ free (GF) mice are unable to produce SCFAs and serve as a model to study how their absence affects colonic motility. GF transit is slower than controls and colonization of these mice improves gastrointestinal (GI) transit and serotonin (5-HT) levels. Our aim was to determine the role SCFAs play in improving transit, and whether this is dependent on mucosal 5-HT signaling. Methods: Motility was assessed in GF mice via spatiotemporal mapping with intraluminal perfusion of either PBS or SCFA cocktail. Outflow from the colon was recorded to quantify propulsive contractions. Motility was then assessed in TPH1-KO mice with PBS, butyrate and then propionate. GPR43 and 5-HT staining was performed in control and GF colons. Mice were then given chow diet or high sugar diet (HSD) and motility was recorded. Fecal pellets were taken at baseline and just prior to motility experiments and SCFA levels were measured with mass spectrometry. Results: GF mice exhibit significantly lower proportion of propulsive contractions, lower volume of outflow per contraction and slower velocity of contractions compared to controls. SCFAs changed the motility patterns to that of the controls in all parameters. Butyrate administration significantly increased the proportion of propulsive contractions in controls, yet failed to in TPH1 KO mice. Propionate significantly inhibited propulsive contractions in both mice. HSD-fed mice were not different from chow-fed mice in any parameter. No SCFA was significantly reduced, but the change in butyrate concentration was significantly associated with LDC frequency. Conclusions: Our results reveal significant abnormalities in the propulsive nature of colon motor patterns in GF mice, explaining the decreased transit time in in vivo studies. We show that butyrate, not propionate, activates propulsive motility and that this requires mucosal 5-HT, possibly released by ECs. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22160 |
| Date | 11 1900 |
| Creators | Vincent, Alexander |
| Contributors | Huizinga, Jandirk, Medical Sciences (Division of Physiology/Pharmacology) |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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