Butyrate is a natural substance present in biological liquids and tissues. The present paper aims to give an update on the biological role of butyrate in mammals, when it is naturally produced by the gastrointestinal microbiota or orally ingested as a feed additive. Recent data concerning butyrate production delivery as well as absorption by the colonocytes are reported. Butyrate cannot be detected in the peripheral blood, which indicates fast metabolism in the gut wall and/or in the liver. In physiological conditions, the increase in performance in animals could be explained by the increased nutrient digestibility, the stimulation of the digestive enzyme secretions, a modification of intestinal luminal microbiota and an improvement of the epithelial integrity and defence systems. In the digestive tract, butyrate can act directly (upper gastrointestinal tract or hindgut) or indirectly (small intestine) on tissue development and repair. Direct trophic effects have been demonstrated mainly by cell proliferation studies, indicating a faster renewal of necrotic areas. Indirect actions of butyrate are believed to involve the hormono–neuro–immuno system. Butyrate has also been implicated in down-regulation of bacteria virulence, both by direct effects on virulence gene expression and by acting on cell proliferation of the host cells. In animal production, butyrate is a helpful feed additive, especially when ingested soon after birth, as it enhances performance and controls gut health disorders caused by bacterial pathogens. Such effects could be considered for new applications in human nutrition.

The consequences of early-life nutritional programming in man and other mammalian species have been studied chiefly at the metabolic level. Very few studies, if any, have been performed in the gastrointestinal tract (GIT) as the target organ, but extensive GIT studies are needed since the GIT plays a key role in nutrient supply and has an impact on functions of the entire organism. The possible deleterious effects of nutritional programming at the metabolic level were discovered following epidemiological studies in human subjects, and confirmed in animal models. Investigating the impact of programming on GIT structure and function would need appropriate animal models due to ethical restrictions in the use of human subjects. The aim of the present review is to discuss the use of pigs as an animal model as a compromise between ethically acceptable animal studies and the requirement of data which can be interpolated to the human situation. In nutritional programming studies, rodents are the most frequently used model for man, but GIT development and digestive function in rodents are considerably different from those in man. In that aspect, the pig GIT is much closer to the human than that of rodents. The swine species is closely comparable with man in many nutritional and digestive aspects, and thus provides ample opportunity to be used in investigations on the consequences of nutritional programming for the GIT. In particular, the ‘sow–piglets’ dyad could be a useful tool to simulate the ‘human mother–infant’ dyad in studies which examine short-, middle- and long-term effects and is suggested as the reference model.

The effect of sodium butyrate (SB) supplementation in milk replacer (MR) or in starter mixture (SM) or in both MR and SM on performance, selected blood parameters, and rumen development in newborn calves was determined. Twenty-eight male calves with a mean age of 5 (±1) d were randomly allocated into 1 of 4 groups (7 animals per group) and fed (1) MR and SM, both without SB (MR(-) and SM(-), respectively); (2) MR(-) and SM supplemented with SB encapsulated within a triglyceride matrix (SM(+), 0.6% as fed; 30:70 butyrate-to-triglyceride matrix); (3) MR supplemented with crystalline SB (MR(+), 0.3% as fed) and SM(-); or (4) MR(+) and SM(+). The MR was offered in an amount equal to 10% of the initial body weight (BW) of each calf. The SM was blended with whole corn grain (50/50; wt/wt) and offered ad libitum as a starter diet (0.3% encapsulated-within-triglyceride matrix SB when SM(+) was fed) from the first day of the trial. Calves were slaughtered at d 21 of a trial (mean age 26±1 d). Addition of SB into MR (MR(+)) positively affected BW and average daily gain, tended to decrease the number of days with electrolyte therapies from d 0 to 7, and tended to positively affect fecal consistency from d 8 to 14 of the trial. Inclusion of SB into SM (SM(+)) increased starter diet intake from d 15 to 21, decreased the number of days with scours, and tended to decrease the number of days with electrolyte therapies in the whole trial period. Both MR(+) and SM(+) increased plasma glucose in the whole trial period and MR(+) increased total serum protein at d 14. The SM(+) increased plasma glucagon-like peptide-2 (GLP-2) concentration at d 7 of the trial when compared with the concentration at d 0. Both MR(+) and SM(+) increased reticulorumen weight and papillae length and width. Based on these results, it can be concluded that addition of SB in MR positively affected BW gain, health, and some metabolic intermediates of calves and it stimulated rumen development indirectly, whereas SB supplementation in SM stimulated rumen development directly. Addition of SB both in MR and SM could be recommended for rearing calves.

In milk-fed calves, the effects of sodium-butyrate (Na-butyrate) to replace flavomycin on growth performance and some mechanisms involved were studied. Pancreatic and intestinal morphology, digestive enzyme activities, plasma gut regulatory peptide concentrations, and expression of their receptors in the gastrointestinal tract were measured. Gastrointestinal tract defense systems were examined by measuring protein levels of 2 heat-shock proteins (HSP27 and HSP70). The calves were randomly allocated into 2 groups fed the same basic diet with flavomycin as an antimicrobial growth promoter or with Na-butyrate (3 g/kg of dry matter). Sodium-butyrate disappeared quickly in the upper gut and was not found in circulating blood. Supplementation with Na-butyrate enhanced growth rate and improved feed conversion into body weight gain compared with the flavomycin group. Supplementation with Na-butyrate was likely associated with an improvement in efficacy of the gastrointestinal tract digestive capacities expressed by enhanced production of digestive enzymes and increased absorptive capacities in the upper small intestine. The effects could have been controlled by insulin-like growth factor-1 but probably not by any of the cholecystokinin/gastrin peptide family. Concentrations of HSP27 and HSP70 were increased in stomach and colon of calves receiving Na-butyrate, thereby assuring protection of cells with intensive metabolism (chaperone function). In conclusion, beneficial effects of Na-butyrate on maturation of gastrointestinal functions were shown in milk-fed calves and may be applied to young mammals of other species.

Promotion of microbial butyrate production in the reticulorumen is a widely used method for enhancing forestomach development in calves. Additional acceleration of gastrointestinal tract (GIT) development, both the forestomach and lower parts of the GIT (e.g., abomasum, intestine, and also pancreas), can be obtained by dietary butyrate supplementation. For this purpose, different sources (e.g., butyrate salts or butyrins), forms (e.g., protected or unprotected), methods (e.g., in liquid feed or solid feed), and periods (e.g., before or after weaning) of butyrate administration can be used. The aim of this paper was to summarize the knowledge in the field of butyrate supplementation in feeds for newborn calves in practical situations, and to suggest directions of future studies. It has been repeatedly shown that supplementation of unprotected salts of butyrate (primarily sodium salt) in milk replacer (MR) stimulates the rumen, small intestine, and pancreas development in calves, with a supplementation level equating to 0.3% of dry matter being sufficient to exert the desired effect on both GIT development and growth performance. On the other hand, the effect of unprotected butyrins and protected forms of butyrate supplementation in MR has not been extensively investigated, and few studies have documented the effect of butyrate addition into whole milk (WM), with those available focusing mainly on the growth performance of animals. Protected butyrate supplementation at a low level (0.3% of protected product in DM) in solid feed was shown to have a potential to enhance GIT development and performance of calves fed MR during the preweaning period. Justification of this form of butyrate supplementation in solid feed when calves are fed WM or after weaning needs to be documented. After weaning, inclusion of unprotected butyrate salts in solid feed was shown to increase solid feed intake, but the effect on GIT development and function has not been determined in detail, and optimal levels of supplementation are also difficult to recommend based on available reports. Future studies should focus on comparing different sources (e.g., salts vs. esters), forms (e.g., protected vs. unprotected), and doses of supplemental butyrate in liquid feeds and solid feeds and their effect not only on the development of rumen, abomasum, and small intestine but also the omasum and large intestine. Furthermore, the most effective source, form, and dose of supplemental butyrate in solid feed depending on the liquid feed program (e.g., MR or WM), stage of rearing (e.g., pre- or postweaning), and solid composition (e.g., lack or presence of forage in the diet) need to be determined.

The objective of the study was to determine the effect of different liquid feeds on calf small intestine and rumen development. Twenty-one bull calves (5 ± 1 d old) were randomly allocated to 3 groups and fed whole milk (WM), milk replacer (MR; 22% CP and 17.5% fat), or MR supplemented with sodium butyrate (MR+SB; 0.3% as fed). Liquid feed dry matter intake was equal between treatments and amounted to 1% of BW at the beginning of the trial. Starter diet was offered ad libitum. Animals were slaughtered at 26 (± 1) d of age. Calves fed WM had higher average daily gain in the whole trial and higher starter diet dry matter intake between d 15 to 21 of the trial as compared with calves fed MR and MR+SB. Calves fed MR lost on average 1.4 kg of BW within first 14 d of the trial and their BW tended to be lower at d 7, 14, and 21 of the study as compared with calves fed MR+SB. The empty jejunum and ileum weight, crypt depth, mitotic index in the middle jejunum were higher, and apoptotic index tended to be lower in calves fed WM as compared with calves fed MR and MR+SB. Calves fed WM also had higher aminopeptidase N activity in the middle jejunum and tended to have higher maltase activity in the distal jejunum as compared with calves fed MR and MR+SB. The mitotic index was higher and apoptotic index was lower in the middle jejunum, and aminopeptidase A activity tended to be higher in the distal jejunum of calves fed MR+SB as compared with those fed MR. Calves fed WM had greater papillae length and width, and tended to have greater muscle layer thickness as compared with calves fed MR and MR+SB. Reticulorumen weight, reticulorumen weight expressed as percent of whole stomach weight, and papillae length and width were higher in calves fed MR+SB as compared with those fed MR. Additionally, calves fed WM had higher plasma glucose and urea in the whole trial period as compared with calves fed MR and MR+SB, and plasma glucose was higher in calves fed MR+SB as compared with those fed MR. Significant positive Pearson correlations were found between small intestine and reticulorumen weights as well as between activity of brush border lactase, maltase, aminopeptidase A, and aminopeptidase N and reticulorumen weight. Different liquid feeds affect small intestine development, animal growth, solid feed intake and metabolic status of calves and this effect can indirectly influence the development of forestomachs.