A lack of information on the intestinal microbiome of neonatal calves prevents the use of microbial intervention strategies to improve calf gut health. This study profiled the taxonomic and functional composition of the small intestinal luminal microbiome of neonatal calves using whole-genome sequencing of the metagenome, aiming to understand the dynamics of microbial establishment during early life. Despite highly individualized microbial communities, we identified two distinct taxonomy-based clusters from the collective luminal microbiomes comprising a high level of either Lactobacillus or Bacteroides. Among the clustered microbiomes, Lactobacillus-dominant ileal microbiomes had significantly lower abundances of Bacteroides, Prevotella, Roseburia, Ruminococcus, and Veillonella compared to the Bacteroides-dominated ileal microbiomes. In addition, the upregulated ileal genes of the Lactobacillus-dominant calves were related to leukocyte and lymphocyte chemotaxis, the cytokine/chemokine-mediated signaling pathway, and inflammatory responses, while the upregulated ileal genes of the Bacteroides-dominant calves were related to cell adhesion, response to stimulus, cell communication and regulation of mitogen-activated protein kinase cascades. The functional profiles of the luminal microbiomes also revealed two distinct clusters consisting of functions related to either high protein metabolism or sulfur metabolism. A lower abundance of Bifidobacterium and a higher abundance of sulfur-reducing bacteria (SRB) were observed in the sulfur metabolism-dominant cluster (0.2% ± 0.1%) compared to the protein metabolism-dominant cluster (12.6% ± 5.7%), suggesting an antagonistic relationship between SRB and Bifidobacterium, which both compete for cysteine. These distinct taxonomic and functional clusters may provide a framework to further analyze interactions between the intestinal microbiome and the immune function and health of neonatal calves. IMPORTANCE Dietary interventions to manipulate neonatal gut microbiota have been proposed to generate long-term impacts on hosts. Currently, our understanding of the early gut microbiome of neonatal calves is limited to 16S rRNA gene amplicon based microbial profiling, which is a barrier to developing dietary interventions to improve calf gut health. The use of a metagenome sequencing-based approach in the present study revealed high individual animal variation in taxonomic and functional abundance of intestinal microbiome and potential impacts of early microbiome on mucosal immune responses during the preweaning period. During this developmental period, age- and diet-related changes in microbial diversity, richness, density, and the abundance of taxa and functions were observed. A correlation-based approach to further explore the individual animal variation revealed potential enterotypes that can be linked to calf gut health, which may pave the way to developing strategies to manipulate the microbiome and improve calf health.

Oxidative stress is the imbalanced redox status between oxidant production and their scavengers leading to intestinal physiological dysfunction. However, the role of systemic and local oxidative status during neonatal calf diarrhea is not known. This study assessed systemic (serum) and local (fecal) oxidative status when calves either naturally developed diarrhea or naturally recovered. Healthy calves were enrolled in the study at d 18 of age, and their health status was monitored from the enrollment. Based on their enteric health status on d 21 and 28, calves were grouped as continuous diarrhea from d 21 to 28 (n = 14), diarrhea at d 21 but recovered at d 28 (DH group, n = 19), healthy at d 21 but developed diarrhea at d 28 (HD group, n = 15), and healthy throughout the study (HH group, n = 16). Serum and fecal samples were collected at d 21 and 28 from all calves in the morning 2 h after feeding. Dynamics of oxidative stress indicators including reactive oxygen species (ROS), malondialdehyde (MDA), H₂O₂, 8-hydroxy-2'-deoxyguanosine (8-OHDG), glutathione peroxidase, superoxide dismutase, catalase (CAT), and total antioxidant capacity and inflammatory indicators TNF-α, IL-1β, IL-4, IL-6, IL-10, and IFN-γ were evaluated using serum samples. In addition, fecal oxidative stress indicators ROS and MDA were measured. Serum ROS, MDA, 8-OHDG, as well as fecal ROS and MDA, were higher, whereas serum CAT and H₂O₂ were lower in diarrheic calves than those of healthy calves. Serum ROS, MDA, and 8OHDG and fecal ROS and MDA increased in the HD group from d 21 to 28 as they developed diarrhea. In contrast, all these oxidative stress markers decreased in the DH group from d 21 to 28 as they recovered. However, serum H₂O₂ had an opposite changing trend, which became lower in the HD group and higher in the DH group at d 28. In conclusion, both systemic and local oxidative stress markers and cytokine profiles altered as calves moved from being healthy to having diarrhea or vice versa. Serum ROS, MDA, and 8-OHDG can be used to develop biomarkers to screen calves prone to enteric infections during the preweaning period.

This comprehensive review highlights the intricate interplay between maternal factors and the co-development of the microbiome and immune system in neonatal calves. Based on human and mouse studies, multiple prenatal and postnatal factors influence this process by altering the host-associated microbiomes (gut, respiratory tract, skin), microbial colonization trajectories, and priming of the immune systems (mucosal and systemic). This review emphasizes the importance of early-life exposure, highlighting postnatal factors that work in synergy with maternal factors in further fine-tuning the co-development of the neonatal microbiome and immunity. In cattle, there is a general lack of research to identify the maternal effect on the early colonization process of neonatal calves (gut, respiratory tract) and its impact on the priming of the immune system. Past studies have primarily investigated maternal effects on the passive transfer of immunity at birth. The co-development process of the microbiome and immune system is vital for lifelong health and production in cattle. Therefore, comprehensive research beyond the traditional focus on passive immunity is an essential step in this endeavor. Calf microbiome research reports the colonization of diverse bacterial communities in newborns, which is affected by the colostrum feeding method immediately after birth. In contrast to human studies reporting a strong link between maternal and infant bacterial communities, there is a lack of evidence to clearly define cow-to-calf transmission in cattle. Maternal exposure has been shown to promote the colonization of beneficial bacteria in neonatal calves. Nonetheless, calf microbiome research lacks links to early development of the immune system. An in-depth understanding of the influence of maternal factors on microbiomes and immunity will improve the management of pregnant cows to raise immune-fit neonatal calves. It is essential to investigate the diverse effects of maternal health conditions and nutrition during pregnancy on the gut microbiome and immunity of neonatal calves through collaboration among researchers from diverse fields such as microbiology, immunology, nutrition, veterinary science, and epidemiology.

The diverse pioneer microbial community colonizing the mammalian gastrointestinal tract is critical for the developing immune system. Gut microbial communities of neonates can be affected by various internal and external factors, resulting in microbial dysbiosis. Microbial dysbiosis during early life affects gut homeostasis by changing metabolic, physiological, and immunological status, which increases susceptibility to neonatal infections and long-term pathologies. Early life is crucial for the establishment of microbiota and the development of the host immune system. Therefore, it provides a window of opportunity to reverse microbial dysbiosis with a positive impact on host health. Recent attempts to use microbial interventions during early life have successfully reversed dysbiotic gut microbial communities in neonates. However, interventions with persistent effects on microbiota and host health are still limited. This review will critically discuss microbial interventions, modulatory mechanisms, their limitations, and gaps in knowledge to understand their roles in improving neonatal gut health.

Digital dermatitis (DD) is a costly hoof infection, causing lameness and pain in feedlot cattle. DD lesions can develop nonlinearly through a series of clinical stages, which can be classified by Dopfer’s M-stage scoring system. This widely adopted lesion scoring system recognizes five DD stages, where M1 (early lesion), M2 (acute ulcerative lesion), and M4.1 (chronic proliferative lesion with new developing lesion) are considered active but separate stages of the disease. This study assessed the skin surface microbiota of the active DD lesions of feedlot cattle. The DD lesions from three commercial feedlots were swabbed and then scored according to Dopfer’s M-stage scoring system. Swab samples were collected from 12 M2- and 15 M4.1-stage lesions. A total of 21 control swab samples from healthy contralateral feet (DD control) were classified as stage M0. An additional six skin swabs (M0) were collected from completely healthy (CH control) cattle with no lesions. The bacterial communities of active DD lesions (M2 and M4.1) and healthy skin (M0) were profiled using 16S amplicon sequencing. Diversity analyses showed that the hoof bacterial communities of M2 and M4.1 lesions were each distinct from those of M0 skin. However, the bacterial communities between the two active lesion stages were not different from each other. A significant increase in the relative abundance of Spirochaetota and Fusobacteriota and an overall decrease in bacterial diversity contributed to the altered bacterial communities in M2 and M4.1 lesions compared to those of healthy skin (M0). Although stages M2 and M4.1 are considered clinically different stages, the lesion-associated bacterial community is similar between the two active stages.

The effect of adding unhydrated calcium oxide (CaO) to corn silage (CS) or barley straw (BS) in a total mixed ration on growth performance, digestibility, blood parameters, and carcass characteristics was evaluated in backgrounding and finishing beef steers. Sixty Angus × beef steers were fed one of 4 diets, containing CS or BS (replacing CS at 12% diet dry matter (DM)) with or without 1% DM CaO replacing CaCO ₃ . During backgrounding, CaO reduced ( P ≤ 0.04) weight gain, average daily gain, and gain:feed while only final body weight was reduced ( P = 0.05) during finishing. Feed efficiency and diet digestibility were greater ( P ≤ 0.05) for CS than BS diets. During backgrounding and finishing, CaO increased ( P = 0.02) crude protein and reduced ( P < 0.01) neutral detergent fibre digestibility, respectively. Adding CaO to the backgrounding diet increased ( P ≤ 0.01) serum amyloid-A and serum cortisol concentrations. The CaO reduced ( P ≤ 0.02) hot carcass weight and dressing percentage compared to control, while BS reduced ( P ≤ 0.02) ribeye area and grade fat compared to CS. Substituting BS for CS and including CaO decreased feed efficiency, carcass yield, and income over feed cost in feedlot steers.