Abstract
Background: Butyrate protects against ischemic injury to the small intestine by reducing inflammation and maintaining the structure of the intestinal barrier, but is expensive, short-lived, and cannot be administered easily due to its odor. Lactate, both economical and more palatable, can be converted into butyrate by the intestinal microbiome. This study aimed to assess in a rat model whether lactate perfusion can also protect against intestinal ischemia.Materials and Methods: Rat intestinal segments were loaded in an in vitro bowel perfusion device, and water absorption or secretion was assessed based on fluorescence of FITC-inulin, a fluorescent marker bound to a biologically inert sugar. Change in FITC concentration was used as a measure of ischemic injury, given the tendency of ischemic cells to retain water. Hematoxylin and eosin-stained sections at light level microscopy were examined to evaluate intestinal epithelium morphology. Comparisons between the data sets were paired Student t-tests or ANOVA with p < 0.05 performed on GraphPad.Results: Lactate administration resulted in a protective effect against intestinal ischemia of similar magnitude to that observed with butyrate. Both exhibited approximately 1.5 times the secretion exhibited by control sections (p = 0.03). Perfusion with lactate and methoxyacetate, a specific inhibitor of lactate-butyrate conversion, abolished this effect (p = 0.09). Antibiotic treatment also eliminated this effect, rendering lactate-perfused sections similar to control sections (p = 0.72). Perfusion with butyrate and methoxyacetate did not eliminate the observed increased secretion, which indicates that ischemic protection was mediated by microbial conversion of lactate to butyrate (p = 0.71).Conclusions: Lactate's protective effect against intestinal ischemia due to microbial conversion to butyrate suggests possible applications in the transplant setting for reducing ischemic injury and ameliorating intestinal preservation during transport.
Highlights
Ischemia occurs when the blood supply to the small bowel is occluded, and if ischemia is followed by reperfusion, reoxygenation of the tissue occurs
We hypothesized that the normal gut microbiome could locally protect against ischemia in the gut epithelium by metabolism of lactate to butyrate: here we present novel data using an intestinal perfusion unit (IPU) as well as histopathology to confirm this hypothesis
After hematoxylin and eosin staining, cross-sections of rat ileum showed an overall normal morphology in control intestines not exposed to ischemia, exhibiting only sub-epithelial blebbing at the tip of the villus (Figure 2A, grade 1 in the Park-Chiu ischemia histopathological classification)
Summary
Ischemia occurs when the blood supply to the small bowel is occluded, and if ischemia is followed by reperfusion, reoxygenation of the tissue occurs. Intestinal ischemia and ischemia reperfusion injury (IRI) are commonly encountered in several clinical conditions including: atherosclerosis, hypotension, blood clots, hernias, cardiac and mesenteric surgery, venous thrombosis, necrotizing enterocolitis, trauma, shock, abdominal aortic surgery, and small bowel transplantation. Butyrate protects against ischemic injury to the small intestine by reducing inflammation and maintaining the structure of the intestinal barrier, but is expensive, short-lived, and cannot be administered due to its odor. Lactate, both economical and more palatable, can be converted into butyrate by the intestinal microbiome. This study aimed to assess in a rat model whether lactate perfusion can protect against intestinal ischemia
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