Systemic chronic inflammation (SCI) is a key driver of non-communicable diseases. Early-life stressors disrupt intestinal homeostasis, promoting SCI, but the mechanisms are unclear. Using translational models, we identify dysregulated iron homeostasis as a pivotal disruptor of intestinal barrier integrity. Single-cell profiling reveals that neutrophils and macrophages mediate iron-dependent mucosal defense. Stress induces iron overload in gut epithelial cells and macrophages, a process governed by the transcription factor MITF. MITF-mediated iron dysregulation in macrophages is associated with neutrophil recruitment to the lamina propria, concomitant with elevated levels of the CXCL8, synchronizing with hepatic inflammatory and metabolic dysregulation via the gut-liver axis. Mechanistically, abnormal iron homeostasis couples with interferon signaling, and MITF modulates iron-related genes (FTH1, TFRC, and FRRS1). Therapeutic mitigation of iron dyshomeostasis preserves barrier function and attenuates systemic inflammation. Our findings identify MITF as a key regulator of gut-liver inflammatory cascades and nominate abnormal iron homeostasis as a target for early-life inflammatory disorders.

This study was conducted to investigate the effects of coenzyme Q10 (CoQ) dietary supplementation on growth performance, rumen fermentation, diarrhea frequency, and serum biochemical metabolites of pre-weaned Holstein dairy calves. Forty-five Holstein female calves (37.86 ± 2.38 kg of body weight [BW]; 1 d of age) were randomly assigned into 1 of the 3 treatments: a control group (Q0; without CoQ supplementation) and CoQ supplementation at low dose (Q50; 50 mg/kg dry matter [DM] of CoQ) or high dose (Q100; 100 mg/kg of CoQ) (n = 15). All experimental calves were fed pasteurized whole milk twice daily (06:30 and 17:00) starting from d 2 of age. From d 61 to 70, the calves were gradually weaned following a step-down approach. Calves had free access to clean water and the starter diet, which was introduced from d 7 onward. The study terminated on d 70. The results showed that calves supplemented with both low and high doses of CoQ had significantly higher average daily gain (linear, P = 0.007) and dry matter intake (DMI, linear, P < 0.001) compared with the Q0 group. There was a treatment by age interaction for BW (P < 0.001), where BW at 10 weeks of age was greater at Q50 and Q100 groups than at the Q0 group. Diarrhea frequency from 1 to 5 weeks of age was significantly affected by treatment (P = 0.026), with Q100 calves showing the lowest values. At 10 weeks of age, the Q100 calves showed higher serum total antioxidant capacity (linear, P = 0.012), superoxide dismutase (linear, P = 0.018), glutathione peroxidase (linear, P = 0.012), and β-hydroxybutyrate (linear, P = 0.006) compared with the Q0 group. The serum malondialdehyde was lower in Q100 calves than Q0 calves (linear, P = 0.015). Compared with the Q50 and Q0 groups, serum contents of insulin, growth hormone, and non-esterified fatty acids increased in calves receiving high CoQ dose (linear, P = 0.006, 0.012, 0.006, respectively). Conversely, the Q50 calves showed higher serum glucose compared with the other treatments (quadratic, P = 0.003). The results of the present study suggest that the supplementation of CoQ to milk may promote growth performance, health status, blood metabolites, and hormones, and improve the antioxidant capacity of the Holstein dairy calves. The use of CoQ may be an alternative to feeding antibiotics at 100 mg/kg DM to improve calf health and decrease diarrhea frequency.

Dairy cow health involves host-microbiome interactions. This review characterized microbial landscapes across anatomical sites in dairy cows-including the gastrointestinal tract, respiratory system, reproductive tract, mammary gland, and skin-and examines their associations with diseases. We elucidated how site-specific dysbiosis drives systemic conditions such as mastitis and ketosis through inter-organ axes. Finally, we evaluated emerging microbiome-based modulation strategies and their application prospects in dairy farming.

Feeding patterns significantly influence goat meat aroma profiles, which are closely related to muscle lipid composition. This relationship is especially significant for indigenous breeds like the Arbas cashmere goat, whose distinctive meat aroma has been traditionally recognized. Despite the known correlation between lipid metabolism and aroma formation, the specific mechanisms by which grazing vs. housed feeding systems modulate these processes in indigenous goat breeds remain poorly characterized. This study employed a comparative approach using integrated foodomics and lipidomics to investigate aroma profiles and lipid compositions in the longissimus thoracis et lumborum (LTL) muscle of Arbas cashmere goats raised under contrasting grazing and housed feeding systems. The volatile profile suggests that fruity and milky notes primarily characterized the aroma of the LTL muscle in Arbas cashmere goats. However, notable differences were observed between grazing and housed feeding goats in terms of their aroma profiles. (Z)-4-Heptenal, ethyl hexanoate, ethyl decanoate, ethyl octanoate, ethyl acetate and ethyl 3-methylbutyrate were identified as key contributors to meat aroma. Differences in intramuscular fat, triglycerides, and phospholipid content were also detected between groups. Lipidomics analysis identified 1,465 lipid species, among which PC (15:0/22:6) was uniquely involved in glycerophospholipid metabolism, arachidonic acid metabolism and α-linolenic acid metabolism pathways, suggesting a central role in the synthesis of aroma-related compounds. These findings demonstrate that feeding systems modulate meat flavor through lipid metabolism pathways, particularly via differential accumulation of key aroma volatiles and targeted alterations in glycerophospholipid metabolism, providing a scientific basis for optimizing housed feeding strategies to enhance Arbas cashmere goat meat quality.

This study evaluated the effects of replacing alfalfa (Medicago sativa) with Sesbania cannabina hay on growth performance, nutrient digestibility, and ruminal microecology in fattening lambs. Forty 3-month-old Aohu crossbred lambs (initial BW: 22.08 ± 0.31 kg) received five isoenergetic, isonitrogenous diets in which S. cannabina hay replaced 0% (CON), 25%, 50%, 75%, or 100% of alfalfa during a 60-day trial. Growth traits, nutrient digestibility, rumen fermentation, enzyme activities, serum biochemical parameters, ruminal microbiota, and metabolomic profiles were evaluated. Substitution did not affect final body weight, average daily gain, or feed conversion ratio (p > 0.05), but nutrient utilization and ruminal fermentation differed among replacement treatments. The 50–100% replacement groups showed higher digestibility of crude protein, ether extract, and fiber, together with higher ruminal protease, cellulase, hemicellulase, and α-amylase activities (p < 0.05). Total volatile fatty acid concentrations were higher in the 50–100% replacement groups, whereas the acetate-to-propionate ratio was lower in all substituted groups. Serum biochemical parameters indicated changes related to protein metabolism without evidence of adverse health effects. Multi-omics analyses revealed distinct differences in ruminal bacterial communities and metabolic profiles among replacement treatments. The 25% replacement group showed relatively limited microbial and metabolic changes. The 75% replacement group exhibited greater bacterial diversity, enrichment of Prevotellaceae_NK3B31_group and Streptococcus, coordinated microbe–metabolite associations, and changes in bile acid and cholesterol metabolism. Complete substitution was associated with more extensive microbial remodeling and lower abundances of several functional metabolites, without additional benefits to growth performance.

[This corrects the article DOI: 10.3389/fvets.2025.1631972.].

ABSTRACT This study investigated the effects of a fermented compound Chinese herbal medicine (FCHM) on growth performance, antioxidant capacity, immune function, and gastrointestinal microbiota in suckling lambs. FCHM consisted of 10 herbs fermented with Candida utilis and Bacillus subtilis . Sixty twin Hu lambs (15 days) were randomly fed a basal diet (CON) or the diet supplemented with 0.6% FCHM (Treat) for 45 days. The results indicated that the Treat group exhibited a significant increase in average daily gain (ADG) ( P < 0.05). Serum analyses revealed elevated levels of growth hormone (GH), insulin-like growth factor-1 (IGF-1), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glucose (GLU), whereas malondialdehyde (MDA) and pro-inflammatory cytokines (IL-6 and TNF-α) were reduced ( P < 0.05). In the duodenal mucosa, SOD and GSH-Px activities and T-AOC levels were significantly elevated, while MDA content was notably decreased ( P < 0.05). Ruminal fermentation profiles showed increased concentrations of propionate and total volatile fatty acids (TVFA) in the Treat group ( P < 0.05). Microbiome analysis revealed that FCHM supplementation selectively modulated the ruminal microbial community, enriching beneficial genera such as Prevotellaceae_UC G-003 and Butyrivibrio, while reducing the abundance of potentially harmful genera like Streptococcus, despite no significant changes in the overall community diversity. Metagenomic sequencing further demonstrated the enrichment of KEGG enzymes and carbohydrate-active enzyme genes involved in carbohydrate metabolism and propionate biosynthesis. Correlation network analyses revealed significant associations among specific microbial taxa, serum antioxidant, immune biomarkers, and growth performance. In conclusion, dietary FCHM supplementation improves growth performance in suckling lambs by optimizing ruminal fermentation patterns, selectively regulating gastrointestinal microbiota, and enhancing systemic antioxidant capacity. These findings support the potential of FCHM as a functional feed additive in lamb production systems. IMPORTANCE Enhancing growth performance and ensuring gastrointestinal health during the suckling period are critical for lamb productivity and welfare. In the context of the antibiotic-free mandate in animal feed, we evaluated the effects of a fermented compound Chinese herbal medicine (FCHM) on growth, antioxidant status, immune parameters, and gastrointestinal microbiota in lambs. Our findings demonstrate that FCHM improves average daily gain, enhances systemic and mucosal antioxidant capacity, and modulates ruminal and hindgut microbiota by enriching beneficial taxa and suppressing potentially harmful bacteria. These effects are linked to upregulated microbial functions in carbohydrate metabolism and propionate biosynthesis. This study provides a microbial-based mechanism for FCHM as a natural feed additive to promote lamb growth and gastrointestinal resilience, offering a sustainable strategy to support early-life development in ruminant production systems.

Abstract Background Early weaning is a key strategy to improve lamb production efficiency; however, it inevitably compromises intestinal barrier integrity and function. This study aimed to investigate the effects of epigallocatechin (EGC) on growth performance and intestinal barrier function in weaned lambs, using metagenomics, metabolomics, and intestinal transcriptomics to elucidate the underlying mechanisms. Results Weaning induced oxidative stress, inflammation, and metabolic disruptions in the jejunum. Supplementation with 12.5 mg/kg EGC (LE) significantly improved growth performance, reduced diarrhea incidence (P < 0.05), enhanced mucosal antioxidant capacity (P < 0.001), and strengthened anti-inflammatory ability (P < 0.001). Metagenomic analysis showed that the LE intervention enriched Ruminococcus spp. and reduced the abundance of Slackia. This microbial shift was associated with elevated luminal concentrations of valeric acid and microbial metabolites derived from EGC. Transcriptomic profiling revealed that the intervention upregulated the PPAR signaling pathway, which supports nutrient metabolism and barrier repair. Concurrently, it attenuated aberrant IL-17 signaling and promoted the restoration of mucosal immune homeostasis, indicating a resolution of excessive inflammatory responses. Conclusions Supplementation with 12.5 mg/kg EGC alleviates weaning stress by fostering a beneficial gut microbiota and promoting the production of specific metabolites. These changes reactivate PPAR mediated epithelial repair and dampen pathological immune activation. Low-dose EGC is an effective nutritional strategy to improve intestinal health and growth in weaned ruminants.

Abstract The gut‐mammary axis orchestrates bidirectional crosstalk linking intestinal homeostasis and mammary function through integrated neural, endocrine, and immune pathways. Dysregulation driven by gut microbiota dysbiosis or metabolic dysfunction compromises lactation performance and induces mastitis via pathogen translocation and epigenetic reprogramming. This review systematically discusses the molecular mechanisms underlying microbial metabolite‐mediated mammary development and lactation efficiency, evaluates the impact of gut‐derived pathogens on mammary barrier integrity and inflammatory cascades, explores maternal offspring microbiome transmission for neonatal immunity programming, and proposes precise nutritional strategies targeting microbial immune metabolic networks. Our synthesis of previous research findings aimed to optimize animal productivity, prevent mammary gland disorders, and provide insights for the advancement of the livestock industry.

Abstract Background Methane (CH4) is a metabolic by-product of rumen microbial fermentation, contributing significantly to global warming and dietary energy loss. Elucidating the mechanisms underlying natural variation in rumen methanogenesis is essential for the development of effective CH4 mitigation strategies. Here, we applied rumen metagenomics to identify the microbial mechanisms for differences in enteric CH4 emissions among dairy cows. Results Enteric CH4 emissions from 111 lactating dairy cows under normal feeding conditions were utilized to characterize the natural variation in rumen methanogenesis. Metagenomic analysis revealed that the comprehensive effects of bacteria involved in starch degradation, lactate metabolism, and volatile fatty acid biosynthesis provide distinct amounts of hydrogen for rumen methanogenesis in high-methane-producing (HMP) and low-methane-producing (LMP) cows. Ciliate protozoa were universally abundant in HMP cows (P < 0.05), whereas methanogens enrichment exhibited heterogeneity, with the dominant methanogen Methanobrevibacter exhibiting negative correlations with the other 11 methanogens (P < 0.05). Six nutrient metabolic pathways modulating methanogenesis were identified, and HMP-associated methanogenesis was further driven by upregulated formate metabolism and acetoclastic pathways (P < 0.05). Random forest model analysis screened 34 microbial genera as biomarkers for CH4 production. Conclusions This study excluded extrinsic confounders exist for rumen microbiome and CH4 emissions in dairy cows. These findings elucidated the causal microbial and metabolic mechanisms underlying rumen methanogenesis, providing actionable targets for microbiome-based strategies to mitigate CH4 emissions from livestock farming.

Dairy cattle are a substantial contributor to global agricultural greenhouse gas emissions, primarily producing enteric methane through the ruminal anaerobic fermentation of dietary fiber. As China formally pledges to achieve carbon neutrality before 2060, accurately quantifying these emissions and developing localized mitigation strategies within the livestock sector has become a critical priority. Enteric methane emissions in dairy cattle are not a static physiological baseline; rather, they represent a highly dynamic phenotype profoundly influenced by an intricate network of physiological and environmental parameters. These include the animal’s age, anatomical and ruminal development, parity, lactation stage, and the precise stoichiometric balance of dietary carbohydrates. This review synthesizes extensive experimental data to construct a robust, scientifically logical framework elucidating the profound physiological mechanisms that govern apparent methane emission parameters. Accordingly, this paper reviews our recent research on methane emissions from Holstein dairy cattle across various ages and lactation stages, including heifers, lactating cows, and dry cows. Furthermore, it extensively evaluates the modulation of methanogenesis under diets with varying neutral detergent fiber to non-fibrous carbohydrate (NDF/NFC) ratios, demonstrating that an increased NDF/NFC ratio is positively correlated with higher enteric methane production, yield, and intensity due to the promotion of acetate-type ruminal fermentation. Ultimately, this review aims to provide robust theoretical support for the accurate quantification of enteric methane emissions and the formulation of precision mitigation strategies tailored to specific physiological states.

The aim of this study was to investigate the effects of dietary fat on energy and nitrogen (N) metabolism efficiency, rumen fermentation, and microbiota in twin suckling lambs. Thirty pairs of twin male lambs were randomly divided into two groups with one group receiving a high-fat diet (HF) and the other a normal-fat diet (NF). Two diets (milk replacer and starter) of equal protein and different fat levels. The metabolism test was conducted when the lambs were 50-60 days old, and nine pairs of twin lambs were randomly selected for slaughter to collect rumen fluid at 60 days old. The result showed that fat addition increased the final body weight (BW), ruminal ammonia nitrogen (NH3-N) content, proportion of propionic acid, and estimated methane production (CH4e) (P < 0.05). The high fat diet tended to improve digestive energy (DE), metabolism energy (ME), DE/ME, utilisation of N (0.05 < P < 0.1). However, microbial crude protein (MCP) content, total volatile fatty acids (VFA), acetic acid ratio, and the ratio of acetate to propionate (A:P) were lower than that in the NF group (P < 0.05). Regardless of whether fat is added or not, no different were observed in blood metabolites between the treatment. High-throughput sequencing revealed that fat addition before weaning increased phyla Proteobacteria and genera of Succinivibrio, but decreased the relative abundance of Clostridium IV, Dialister, Roseburia, Acidaminococcus, and Megasphaera genera. These findings indicated that high fat diet improved body weight, energy and nitrogen utilization may by shifting the rumen toward propionate fermentation via the enrichment of Succinivibrio.

This study aimed to investigate the ensiled protein grass (PG) as a novel feed source for lamb production by examining its effects on fattening performance, meat quality and flavor. The results reveal no significant effects of PG silage incorporation on growth performance, carcass characteristics, or serum biochemical parameters of fattening lambs. The sensory quality, nutrient composition, and amino acid profiles of meat also remained unaffected. However, the concentration of C18:3n-3 was significantly higher in the PG diet group, and the levels of C18:2n-6 and C20:3n-6, as well as the ratio of n-6: n-3 PUFA, were lower. Moreover, incorporating PG silage into diets has diversely and significantly impacted the volatile profiles of raw meat and fat tissues. Overall, the ensiled PG could be utilized as a novel and alternative feed ingredient in lamb diets, potentially enhancing the meat's fatty acid composition and the fat's flavor profiles while maintaining fattening performance.

This study evaluates the effects of a compound microecological preparation named ATABG, which is composed of antimicrobial peptide ID13 and Saccharomyces boulardii, on Hu sheep’s growth performance, feed digestibility, and rumen parameters. A total of 40 three-month-old Hu sheep (21.65 ± 0.33 kg) were randomly assigned to two groups: the control group (Con), which received a basal diet, and the experimental group (ATABG), which received the same diet supplemented with 1 g/kg ATABG on a dry matter basis. After a 10-day pre-feeding period to adapt the animals to the experimental diet, dry matter intake and weight gain were recorded during the subsequent 63-day trial period. Body weight was measured on days 1, 21, 42, and 63 of the trial, and animals were slaughtered on day 63 to collect rumen fluid and tissue. Results indicated that ATABG supplementation significantly increased the apparent digestibility of crude protein, neutral detergent fiber, acid detergent fiber, and organic matter (p < 0.05). Rumen fluid analysis revealed increased microbial protein concentration and cellulase activity (p < 0.05) in the ATABG group. Microbiota analysis indicated that ATABG increased the relative abundance of Ruminococcus and Proteobacteria, elevated Firmicutes, and reduced Bacteroidota (p < 0.05). Correlation analysis showed Ruminococcus was positively associated with crude protein digestibility, while Quinella correlated with growth-related indices (r > 0.4, p < 0.05). In conclusion, ATABG supplementation improves protein digestibility and rumen microbial protein synthesis by enriching Ruminococcus and enhancing cellulase activity, potentially optimizing nitrogen utilization in Hu sheep.

The high prevalence of diarrhea in calves raises serious welfare concerns and imposes substantial economic losses on dairy farms. Probiotic strains that produce butyric acid may lower diarrhea incidence and improve gut health. This study evaluated the effects of direct-fed Clostridium beijerinckii R8 on growth performance, plasma biochemistry, and fecal microbiota in neonatal calves. Sixty newborn female calves were blocked by birth weight and randomly allocated to 4 treatments: (1) control (0 cfu/d), (2) low dose (1 × 109 cfu/d), (3) medium dose (1 × 1010 cfu/d), and (4) high dose (1 × 1011 cfu/d). Diarrhea frequency and duration exhibited a significant quadratic response to supplementation, with the lowest values observed at 1 × 1010 cfu/d. Quadratic treatment contrasts were significant for growth performance. Calves receiving 1 × 1010 cfu/d achieved the highest BW, ADG, DMI, body diagonal length, and hip width, together with the lowest feed conversion ratio. Plasma total cholesterol, high-density lipoprotein, BUN, and insulin increased linearly with dose. At 28 d of age, IgG, IgM, total antioxidant capacity, superoxide dismutase, and catalase levels showed linear increases, whereas malondialdehyde declined linearly as dose increased. Fecal microbiota showed both dose-dependent and temporal shifts. On d 28, Lachnoclostridium and Collinsella decreased linearly with dose, whereas Eubacterium_coprostanoligenes_group and Escherichia-Shigella displayed quadratic declines, reaching their lowest relative abundance at 1 × 1010 cfu/d. By d 56, Lachnospiraceae_NK4A136_group and Intestinimonas increased linearly with dose, whereas Bifidobacterium and Lactobacillus showed quadratic responses, with their lowest abundance at 1 × 1011 cfu/d. In conclusion, supplementation of 1 × 1010 cfu/d Clostridium beijerinckii R8 optimally reduced diarrhea, enhanced growth performance, and improved intestinal health by modulating the gut microbiota.

The early weaning of lambs frequently leads to weakened immunity, impaired intestinal function, and increased susceptibility to intestinal disease. Lactobacillus plays a role in regulating immunity, enhancing antioxidant capacity, and maintaining intestinal health. This study aims to isolate a strain of Lactobacillus with favorable probiotic properties from sheep feces and investigate its effects on the intestinal health of early-weaned lambs. In this study, the growth characteristics, acid production capacity, bacteriostatic capacity, bile salt tolerance, gastrointestinal fluid tolerance, self-coagulation capacity, and surface hydrophobicity of Lactobacillus isolated from sheep feces were analyzed for in vitro probiotic properties. Lactobacilli with strong probiotic properties were used for in vivo validation. A total of 72 Hu lambs were allocated into four groups: a ewe-reared group (ER), early-weaning group (EW), low-dose Lactobacillus group (LL), and high-dose Lactobacillus group (HL). Early weaning was performed in the EW, LL, and HL groups at the age of 28 days. Lactobacillus johnsonii M5 (L. johnsonii M5), isolated from sheep feces, exhibited strong probiotic properties in vitro. Feeding EW lambs with a low dose of L. johnsonii M5 significantly reduced their diarrhea rate (p < 0.05). Its supplementation increased the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) in serum and jejunal mucosa and decreased levels of malondialdehyde (MDA) (p < 0.05). Compared to the EW group, serum immunoglobulin G (IgG) levels were significantly increased in the LL group (p < 0.05). Compared to the EW group, feeding with L. johnsonii M5 increased the content of anti-inflammatory cytokines, while reducing the content of pro-inflammatory cytokines in serum and jejunal mucosa (p < 0.05). Feeding early-weaned lambs with L. johnsonii M5 also decreased jejunal crypt depth and increased occludin and claudin-1 in jejunal mucosa (p < 0.05). These findings indicate that feeding early-weaned lambs with L. johnsonii M5 enhances their immunity and antioxidant capacity, improving intestinal health, and mitigates diarrhea in early-weaned lambs.

IntroductionThe juvenile period represents a critical rearing phase in animals, during which rearing quality directly impacts adult productive performance. Plant extracts have been used as feed additives to promote growth, inhibit bacteria, enhance immunity, improve animal health, and ensure the safety of animal products. Therefore, our study aimed to investigate the effects of Euphorbia humifusa extract (EHE) on growth performance, serum biomarkers and antioxidant mechanisms in preweaning calves.MethodsForty-eight newborn calves were randomly allocated to four groups (12 calves/group) and fed milk replacer supplemented with 0 mg (control, CON), 400 mg (Group A), 800 mg (Group B), or 1,200 mg (Group C) of EHE. Body weight and serum biomarkers were measured on d 30 and 60. Network pharmacology was employed to identify EHE-related antioxidant targets, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.ResultsCalves in group C exhibited significantly higher average daily gain (ADG) compared with CON during d 30–60. Both dry matter intake (DMI) and ADG across treatment groups demonstrated a dose-dependent increase. Serum growth hormone (GH) shows the same trend as daily weight gain and feed intake. Serum analysis revealed that superoxide dismutase (SOD) activity in group C was significantly elevated versus CON, Network pharmacology identified 150 potential antioxidant targets of EHE, primarily enriched in pathways associated with cancer, hepatic injury, apoptosis, and viral infection, suggesting immune-modulatory effects.DiscussionBased on these findings, it can be inferred that supplementing milk replacer with EHE enhances calf growth performance, regulating oxidative stress, and it regulates signaling pathways related to immune response and apoptosis through interactions with key targets such as IL6, TP53, MAPK1, AKT1, TNF, BCL2, and ESR1.

This study used Rhodobacter sphaeroides protein (RSP) as an innovative dietary protein source for Holstein dairy calves. We investigated its effects on growth performance, nutrient digestibility, rumen fermentation, and serum metabolites, antioxidants, immunoglobulins, and inflammatory factors. A total of 45 female Holstein calves (mean ± SD, 36.54 ± 1.68 kg of BW; 1 d of age) were randomly assigned to 3 treatment groups and fed either a control diet (CON) or diets with 5.89% or 11.49% RSP (RS1 and RS2, respectively) on a diet DM basis for 14 wk. The inclusion of RSP linearly increased BW and ADG, whereas it quadratically decreased DMI. There was a quadratic effect for gain-to-feed ratio and hip height, with higher mean values for the RS1 group. In addition, the dietary RSP tended to result in a linear increase in the overall withers height and postweaning heart girth. The dietary RSP reduced linearly the digestibility of DM and OM and tended to reduce linearly the digestibility of NDF and ADF. The levels of rumen butyrate showed a linear decrease in RSP calves. There was a quadratic effect for serum aspartate aminotransferase, with the highest value being for RS2 group. Increasing dietary RSP quadratically affected serum triglyceride levels, with the highest value being for the RS1 group. Meanwhile, serum alanine aminotransferase levels were quadratically decreased by RSP, with the RS1 group having the lowest levels. A quadratic trend effect was observed for serum albumin and total protein, with the highest values being in the RS1 group. The levels of lactate dehydrogenase, BUN, malondialdehyde, IL-10, and immunoglobulins decreased linearly with RSP. In contrast, total antioxidant capacity and the levels of superoxide dismutase, catalase, tumor necrosis factor-α, IL-8, and IL-6 increased linearly. In addition, the serum levels of low- and high-density lipoprotein, cholesterol, IL-4, IL-22, and glutathione peroxidase tended to increase linearly with the inclusion of dietary RSP. In conclusion, dietary inclusion of RSP in dairy calves reduced DMI, nutrient digestibility, and serum immunoglobulins levels, particularly at higher inclusion rates, whereas it improved ADG and antioxidant capacity.