Digital dermatitis (DD) poses a major animal welfare concern for the dairy industry, with even broader economic implications for the agricultural industry worldwide. The postbiotic, a Saccharomyces cerevisiae fermentation product (SCFP), has had a positive influence on the innate immune system of cattle, which makes it a potential candidate as a feed supplement as part of a prevention strategy for DD. This study investigated the effect of a commercial SCFP feed supplement compared to a control feed supplement on the production of pro-inflammatory cytokines (IL-1β and IL-6) by peripheral blood mononuclear cells (PBMCs) in Holstein Friesian steers experimentally infected with DD. The results showed that SCFP supplementation was associated with an overall reduced IL-1β production (p = 0.005), particularly prior to experimental inoculation with a DD lesion homogenate. However, the results of the analysis suggest that the innate immune system in the SCFP group became prepared to respond more rapidly to DD infection post-inoculation. During active (M2), chronic (M4), and focal flare-ups (M4.1) of DD, SCFP supplementation resulted in a more rapid secretion of IL-1β (M2: p = 0.038; M4/M4/1: p = 0.034). A more rapid response to DD infection for IL-6 was only found for chronic (M4) and focal flare-ups (M4.1) of DD (p = 0.006). These findings emphasize the difference in cytokine response between various stages of DD in the SCFP group compared to the control, highlighting implications for DD prevention and treatment.

Highly pathogenic avian influenza (HPAI) is a lethal disease of poultry that has recently spilled over into mammals, including dairy cattle and humans, heightening concerns for livestock health, food security, and pandemic emergence. While vaccines that induce neutralizing antibodies against hemagglutinin and neuraminidase provide strain-specific protection, durable cross-subtype immunity requires T-cell responses targeting conserved internal antigens such as nucleoprotein (NP). To leverage these conserved targets, we utilized a previously engineered mosaic nucleoprotein (MNP) incorporating T-cell epitopes from thousands of influenza A virus (IAV) strains, conferring broad protection against epidemic (H3N2) and pandemic (H1N1) IAV in mice. Here, we tested whether precision adjuvancy could differentially imprint adaptive immunity to MNP in cattle. Combination formulations paired the carbomer-based nano-emulsion Adjuplex (ADJ) with either a STING agonist (cyclic dinucleotides; CdN) or a TLR4 agonist (glucopyranosyl lipid A; GLA) to program distinct inflammatory milieus. Both formulations elicited circulating IFN-γ–producing T cell responses and NP-specific antibodies in serum and milk. However, STING activation via CdN generated more potent and consistent cellular and humoral immunity than TLR4 engagement. These data demonstrate that selective activation of innate sensing pathways functionally imprints adaptive immune magnitude and quality in a large animal host. By advancing a broadly protective, T-cell-focused vaccine strategy in cattle, this work supports a One Health framework to mitigate H5N1 transmission risk at the human–animal interface.

Digital dermatitis (DD) is the leading cause of lameness in cattle, posing major animal welfare and economic concerns. Effective prevention strategies are increasingly important given emerging antimicrobial resistance associated with common DD treatments. Supplementation with Saccharomyces cerevisiae fermentation postbiotics (SCFP) has been shown to enhance innate immunity and reduce DD lesion development. This study evaluated the effect of a commercial SCFP supplement on the microbial composition of DD lesions using shotgun metagenomic sequencing to characterize microbial communities and associated antimicrobial resistance genes. Beta diversity analysis revealed that stage M4 DD lesions from SCFP-supplemented cows had a trend for different microbial compositions compared with controls ( P = 0.051). At the genus level, M2 lesions were found to have statistically significant lower abundance of the genera Desulfovibrio , Pseudomonas , Staphylococcus , Anaerotignum , Caproicibacterium , and Bacteroides in the SCFP treatment group compared with the control ( P < 0.05). M2 lesions from the SCFP treatment group were also found to have statistically significant higher abundance of the genera Fusobacterium , Citricoccus , Listeria , and Fundicoccus as compared with the control ( P < 0.05). M4 lesions were found to have statistically significant lower abundance of the genera Blautia and Petrimonas in the SCFP treatment group compared with the control ( P < 0.05). At the species level, M2 lesions were found to have statistically significant lower abundance of the species Desulfovibrio sp. G11 , Anaerotignum sp. MB30-C6 , Caproicibacterium argilliputei , and Prevotella intermedia in the SCFP treatment group compared with the control ( P < 0.05). M2 lesions from the SCFP treatment group were also found to have statistically significant higher abundance of the species Fundicoccus culcitae and Helcococcus ovis as compared with the control ( P < 0.05). Metagenomic analysis identified antimicrobial resistance genes associated with multiple antibiotics commonly used for DD treatment, including tetracyclines, lincosamides, and pleuromutilins. These findings demonstrate the potential for SCFP supplementation to alter the microbial composition of DD lesions while highlighting the ongoing concerns regarding antimicrobial resistance in DD management. IMPORTANCE: Digital dermatitis (DD) causes substantial economic loss and welfare concerns in cattle production systems worldwide. Our findings show that dietary supplementation with Saccharomyces cerevisiae fermentation postbiotics (SCFP) has the potential to alter the microbial ecology of DD lesions. Importantly, this work identifies antimicrobial resistance genes within DD lesions, underscoring the limitations of antibiotic-based control strategies. By linking nutritional supplementation to changes in microbial communities and resistance gene profiles, this study advances understanding of non-antibiotic approaches to disease mitigation and supports the development of sustainable, microbiome-informed management practices in food animal production.