Foals commonly experience diarrhoea in the first weeks of life. Although this condition is rarely life-threatening, it can have significant health consequences. This study investigated whether new-born foals can benefit from a dietary supplement of nucleotides, as already demonstrated in other species. Dietary nucleotides have positive effects on rapidly proliferating tissues and are considered "semi-essential nutrients" since cells have only a limited capacity to synthesize these compounds. The aim of this study was to investigate whether providing foals with a dietary nucleotide supplementation, in the form of an oral paste, was able to affect diarrhoea incidence, systemic immunity, intestinal microbiota and volatile fatty acid production. Thirty new-born standardbred foals, from 3 different premises within the same area, were equally distributed between two groups: one group received an oral paste containing dietary nucleotides (NUCL group), while the other received a placebo paste (CTRL group). Faecal and blood samples were collected on days 1 and 35 after birth. No statistical differences in cytokines (TNF-α, IFN-γ, IL-6, IL-12) or faecal calprotectin levels were found between the two groups, suggesting that the level of nucleotide supplementation used in this study did not have significant effects on the systemic immune system and on the levels of faecal calprotectin. However, the NUCL group showed a lower relative frequency of number of days with diarrhoea (6.12% vs 13.33%
p <
0.002) and greater weight gain compared with the CTRL group (50.3 ± 5.65 kg vs 44.0 ± 8.65 kg
p <
0.05). Total volatile fatty acids, branched volatile fatty acids, acetic acid, propionic acid, butyric acid, succinic acid and iso-butyric acids in faecal samples were all higher in the NUCL group compared with the CTRL group. This outcome may explain an earlier establishment of a gut microbiota in the foals of the NUCL group that was closer to that typical of an adult horse, characterised by predominant fibrolytic populations. Volatile fatty acid production (especially butyric acid) has also been shown to correlate with the intestinal well-being of the horse, supporting the use of dietary nucleotide supplements for improved health and well-being in new-born foals. Although we noted no clear differences in the faecal microbial communities between the two groups, dietary nucleotide supplementation did appear to have a positive clinical outcome, reducing the number of days of diarrhoea and increasing the levels of volatile fatty acids.