The influence of microbial metabolites on human intestinal epithelial cells and macrophages in vitro.
Microbial metabolites may influence the metabolic integrity of intestinal epithelial cells and induce mucosal immune responses. Therefore, we investigated the effects of the microbial metabolites butyrate, iso-valerate, and ammonium on Caco-2 cells and macrophages. Barrier functioning was determined by measuring transepithelial electrical resistance and basolateral recoveries of metabolites. The barrier function of Caco-2 cells remained intact after exposures. Basolateral recoveries ranged from 6.2% to 15.2%. Tumour necrosis factor-alpha and interleukin-10 were measured to determine immune reactions. The Caco-2 cells did not secrete both cytokines. Physiological concentrations of butyrate and iso-valerate stimulated the secretion of tumour necrosis factor-alpha and suppressed the secretion of interleukin-10 by macrophages that are not protected by an epithelial barrier. In contrast, ammonium concentrations as high as those produced by microbiotas of IBD patients suppressed the release of both cytokines when the barrier function is impaired.
van Nuenen
Marleen H M C
MH
TNO Quality of Life, P.O. Box 360, Utrechtseweg 48, 3700 AJ, Utrecht, Zeist, The Netherlands. nuenen@voeding.tno.nl
de Ligt
Rianne A F
RA
Doornbos
Robert P
RP
van der Woude
Janneke C J
JC
Kuipers
Ernst J
EJ
Venema
Koen
K
D000643:Ammonium Chloride / Q000378:metabolism / Q000494:pharmacology; D002087:Butyrates / Q000378:metabolism / Q000494:pharmacology; D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D045782:Hemiterpenes; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000209:etiology / Q000276:immunology / Q000382:microbiology; D016753:Interleukin-10 / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D010421:Pentanoic Acids / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020298:U937 Cells
D002087:Butyrates; D045782:Hemiterpenes; D010421:Pentanoic Acids; D014409:Tumor Necrosis Factor-alpha; D000643:Ammonium Chloride; D016753:Interleukin-10; C008216:isovaleric acid