AUTHOR=Bertacco Alessandra , Dehner Carina A. , Caturegli Giorgio , D'Amico Francesco , Morotti Raffaella , Rodriguez Manuel I. , Mulligan David C. , Kriegel Martin A. , Geibel John P. 

TITLE=Modulation of Intestinal Microbiome Prevents Intestinal Ischemic Injury

JOURNAL=Frontiers in Physiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2017.01064

DOI=10.3389/fphys.2017.01064

ISSN=1664-042X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Materials and Methods:</bold> Rat intestinal segments were loaded in an <italic>in vitro</italic> 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 <italic>t</italic>-tests or ANOVA with <italic>p</italic> &lt; 0.05 performed on GraphPad.</p><p><bold>Results:</bold> 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 (<italic>p</italic> = 0.03). Perfusion with lactate and methoxyacetate, a specific inhibitor of lactate-butyrate conversion, abolished this effect (<italic>p</italic> = 0.09). Antibiotic treatment also eliminated this effect, rendering lactate-perfused sections similar to control sections (<italic>p</italic> = 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 (<italic>p</italic> = 0.71).</p><p><bold>Conclusions:</bold> 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.</p>