Effect of Short‐Chain Fatty Acids on the Human Colonic Mucosa in Vitro

Abstract

Fermentable dietary fiber components are known to stimulate colonic crypt proliferation. As these compounds are rapidly degraded to short-chain fatty acids (SCFAs) by the anaerobic microflora, the hypothesis was tested that this trophic effect of fiber may be mediated by SCFAs. Biopsies were taken from normal cecal mucosa of 45 individuals during routine colonoscopy. They were incubated for 3 hours with sodium salts of SCFAs at physiological concentrations (three SCFAs = acetate 60 mmol/L + propionate 25 mmol/L + butyrate 10 mmol/L; acetate 60 mmol/L; propionate 25 mmol/L; butyrate 10 mmol/L) or equimolar NaCl (control). Cell proliferation was measured autoradiographically by subsequent pulse labeling with [3H]thymidine (1 hour). The labeling index (number of labeled cells divided by the total number of cells) was computed for the crypt as a whole and for five equal crypt compartments (compartment 1 = crypt base, compartment 5 = crypt surface). Cecal crypt proliferation was raised significantly in all incubation experiments with SCFAs. Butyrate (10 mmol/L, increase + 89%) and propionate (25 mmol/L, + 70%) were as effective in stimulating proliferation as the combination of three SCFAs (+103%), although the effect of acetate (+31%) was minor. Increasing the butyrate concentration to 25 mmol/L or 60 mmol/L did not result in a further increase of cell labeling. SCFAs stimulated proliferation in the basal three crypt compartments only. An expansion of the proliferative zone to compartments 4 and 5 was not observed. SCFAs, especially butyrate and propionate, are luminal trophic factors for the cecal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Influência da irrigação de soluções nutricionais no colo excluso de trânsito intestinal: estudo experimental em ratos

“…(23) Quanto a outros aspectos funcionais, sabe-se que os ácidos graxos de cadeia curta aumentam absorção de água e de sódio da luz intestinal. (24,25) Estudos experimentais imputaram à glicose hipertônica, fatores positivos na cicatrização de anastomoses. (19) Outras pesquisas em ratos concluíram que instilação de soluções com concentração elevada de glicose na luz do colo apresenta efeito protetor quanto a prevenção do aparecimento de neoplasias.…”

“…Essa diminuição encontrada encontra-se de acordo com outros estudos anteriormente publicados. (3,8,9,17,25,27,28,29) A totalidade das alterações histológicas, que ocorrem na colite de exclusão (30) , não foi identificada no presente estudo, provavelmente em decorrência do curto espaço de tempo de observação considerado. Pode-se imaginar que com maior tempo de exclusão e a manutenção da condição de derivação intestinal, poderiam encontrar-se alterações histopatológicas mais acentuadas, aproximando-se com achados observados por outros autores.…”

Butyric acid in gastrointestinal tract

“…Według Scheepach i wsp. [7] fizjologiczne stężenie kwasu masło-wego w treści jelita grubego człowieka mieści się w granicach 1-10 mmol/l treści. Z przeglądu piśmiennictwa wynika, że zdecydowana większość publikowanych badań in vitro i in vivo wykonywano z użyciem takich właśnie stężeń kwasu masłowego lub maślanu sodu.…”

Roles of Short-Chain Fatty Acids and their Receptors in Colonic Motility

“…Luminal SCFAs are not only absorbed as nutrients by the intestinal epithelia but also influence various physiological and pathophysiological actions in the intestine as chemical stimuli. For example, SCFAs have been reported to stimulate smooth muscle contractions (19,38,39,42,43), transepithelial chloride secretion (26,67), colonocyte proliferation (48,51), and to prevent colorectal cancer (13). As a remote effect, infusion of SCFAs into the colon (47) or ileum (10,11) have also been reported to inhibit proximal intestinal motility which is variously known as the "colonic brake", "ileal brake" or "ileocolonic brake".…”