This study aimed to evaluate the potential of two new fat-protected butyrate or heptanoate salts to improve gut health and control post-weaning colibacillosis in weaning piglets challenged with enterotoxigenic Escherichia coli (ETEC) F4⁺, particularly focusing on their impact on intestinal microbiota and fermentative activity along the gastrointestinal tract (GIT). Seventy-two 21-d-old pigs were fed a plain diet (CTR) or supplemented with sodium butyrate (BUT) or sodium heptanoate (HPT), both at 0.3%. After a week of adaptation, animals were orally challenged at days 8 and 9 with 5.8 · 10⁹ and 6.6 · 10¹⁰ cfu, respectively, and were euthanised on d 4 and d 8 post-inoculation (PI) (n = 8) to collect blood, digesta and tissue samples and characterise microbial groups, pathogen loads (qPCR), fermentation, ileal histomorphometry and immune markers. Colonic microbiota was analysed by 16S rRNA gene MiSeq sequencing. Supplementing both acid salts did not compensate clinical challenge effects nor performance impairments and neither histomorphometry nor serum biomarkers. Changes in the gastric fermentative activity were registered, BUT reducing lactic acid concentrations (day 8 PI), and with HPT fewer animals presenting detectable concentrations of propionic, butyric and valeric acids. At ileum BUT increased acetic acid concentration (day 8 PI), and both additives reduced short-chain fatty acids (SCFA) in the colon. Increases in enterobacteria and coliforms counts in ileal digesta (day 4 PI, p < 0.10) and mucosa scrapes (p < 0.05) were registered although E. coli F4 gene copies were unaffected. Regarding changes in the colonic microbiota (day 4 PI), Prevotellaceae and Prevotella were promoted with BUT supplementation whereas only minor groups were modified in HPT-treated animals. Summarising, although the pathogen loads or inflammatory mediators remained unresponsive, butyrate and heptanoate showed a significant impact on microbial fermentation along the whole GIT, being able to modify different bacterial groups at the colon. It could be hypothesised that these effects might be mediated by a carry-over effect of the changes observed in gastric fermentation, but possibly also to a better nutrient digestion in the foregut as a result of the reduced colonic SCFA concentrations.

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