Li Ma's research while affiliated with Sichuan Agricultural University and other places

Introduction The risk of ketosis is assessed by monitoring changes in plasma metabolites and cow behavior during the peripartum period. However, little is known about changes in the fecal bile acid and microbiota of cows before parturition. Therefore, this study clarified the bile acid profile and screened potential warning biomarkers in heifers 7 days before calving. Methods Ninety healthy cows were tracked in the transition period, and plasma and feces were collected 7 days before calving, on calving day, and 7 days after calving. The cows were divided into ketosis and healthy groups based on the blood β-hydroxybutyric acid levels from day 7 after calving. The levels of serum biochemical indices were measured at three time points using commercial kits. Ten cows in the ketosis group (KET-7) and 10 healthy cows (HEA-7) were randomly selected 7 days before calving for metabolome and 16S rRNA amplicon sequencing. Results No significant differences in serum energy-related indices were observed 7 days before calving. The major bile acids in the feces of the KET-7 group were non-conjugated secondary bile acids (UnconSBA). Differential bile acids were primarily derived from UnconSBA. The potential ketosis warning metabolite in feces for 7 days before delivery was isodeoxycholic acid. The abundance of Rikenellaaceae-RC9-gut-group in the KET-7 group increased, whereas the abundance of Oscillospiraceae UCG-010 bacteria significantly decreased. Lactobacillus and Prevotella-9 in feces were potential warning biomarkers for ketosis in dairy cows 7 days before calving. The variation in differential bile acids in the plasma, consistent with the feces, was mainly derived from UnconSBA. Lithocholic acid in the plasma was a potential ketosis warning metabolite 7 days before delivery. Conclusion Ketotic cows experienced bile acid metabolism disorders 7 days before calving, and the gut microbiota was closely related to bile acid metabolism disorders. Future studies should investigate the relationship between secondary bile acids and the development of ketosis.

Dairy cows with ketosis have high circulating beta-hydroxybutyric acid (BHBA) concentrations alongside which inflammation is concomitantly developed. Tryptophan (Trp) is an essential amino acid that participates in the regulation of the inflammatory response. However, the association between Trp metabolism and inflammation in dairy cows with ketosis remains unclear. Therefore , blood samples from healthy (n = 10) and ketotic (n = 10) primiparous dairy cows were collected at the calving date and the day of ketosis diagnosis (7 days in milk (7 DIM)). Serum levels of non-esterified fatty acids (NEFA), BHBA, haptoglobin (HP), serum amyloid A (SAA), lipopolysaccha-ride, and cortisol were analyzed. Tryptophan and its metabolites were quantified using liquid chromatography tandem mass spectrometry. At 7 DIM, the concentrations of NEFA, BHBA, HP, and SAA were higher and the levels of Trp, kynurenine (KYN), indoleacetic acid, indole-3-lactic acid, and 3-indoxyl sulfate were lower in the dairy cows with ketosis compared with those in the healthy cows. However, the KYN/Trp and melatonin/Trp ratios increased in the cows with ketosis. At the calving date, the serum lipopolysaccharide levels did not differ between the healthy and ketotic cows, whereas the levels of NEFA, HP, and cortisol increased in the ketotic cows. Correlation analysis showed that Trp deficiency and elevated Trp metabolism in the dairy cows occurred during ketosis. Overall, our results suggest that abnormal Trp metabolism may contribute to the pathogen-esis of ketosis.

The effect of oat β-glucan on intestinal function and growth performance of weaned rabbits were explored by multi-omics integrative analyses in the present study. New Zealand White rabbits fed oat β-glucan [200 mg/kg body weight (BW)] for 4 weeks, and serum markers, colon histological alterations, colonic microbiome, colonic metabolome, and serum metabolome were measured. The results revealed that oat β-glucan increased BW, average daily gain (ADG), average daily food intake (ADFI), and decreased serum tumor necrosis factor-α (TNF-α) interleukin-1β (IL-1β), and lipopolysaccharide (LPS) contents, but did not affect colonic microstructure. Microbiota community analysis showed oat β-glucan modulated gut microbial composition and structure, increased the abundances of beneficial bacteria Lactobacillus , Prevotellaceae_UCG-001 , Pediococcus , Bacillus , etc. Oat β-glucan also increased intestinal propionic acid, valeric acid, and butyric acid concentrations, decreased lysine and aromatic amino acid (AAA) derivative contents. Serum metabolite analysis revealed that oat β-glucan altered host carbohydrate, lipid, and amino acid metabolism. These results suggested that oat β-glucan could inhibit systemic inflammation and protect intestinal function by regulating gut microbiota and related metabolites, which further helps to improve growth performance in weaned rabbits.

Left displaced abomasum (LDA) in postpartum dairy cows contributes to significant economic losses. Dairy cows with LDA undergo excessive lipid mobilization and insulin resistance. Although gut dysbiosis is implicated, little is known about the role of the gut microbiota in the abnormal metabolic processes of LDA. To investigate the functional links among microbiota, metabolites, and disease phenotypes in LDA, we performed 16S rDNA gene amplicon sequencing and liquid chromatography tandem mass spectrometry (LC-MS/MS) of fecal samples from cows with LDA (n = 10) and healthy cows (n = 10). Plasma marker profiling was synchronously analyzed. In the LDA event, gut microbiota composition and fecal metabolome were shifted in circulation with an amino acid pool deficit in dairy cows. Compared with the healthy cows, salicylic acid derived from microbiota catabolism was decreased in the LDA cows, which negatively correlated with Akkermansia, Prevotella, non-esteri-fied fatty acid (NEFA), and b-hydroxybutyric acid (BHBA) levels. Conversely, fecal taurolithocholic acid levels were increased in cows with LDA. Based on integrated analysis with the plasma metabolome, eight genera and eight metabolites were associated with LDA. Of note, the increases in Akkermansia and Oscillospira abundances were negatively correlated with the decreases in 4-pyridoxic acid and cytidine levels, and positively correlated with the increases in NEFA and BHBA levels in amino acid deficit, indicating pyridoxal metabolism-associated gut dysbiosis and lipolysis. Changes in branched-chain amino acids implicated novel host-microbial metabolic pathways involving lipolysis and insulin resistance in cows with LDA. Overall, these results suggest an interplay between host and gut microbes contributing to LDA pathogenesis. IMPORTANCE LDA is a major contributor to economic losses in the dairy industry worldwide; however, the mechanisms associated with the metabolic changes in LDA remain unclear. Most previous studies have focused on the rumen microbiota in terms of understanding the contributors to the productivity and health of dairy cows; this study further sheds light on the relevance of the lower gut microbiota and its associated metabolites in mediating the development of LDA. This study is the first to characterize the correlation between gut microbes and metabolic phenotypes in dairy cows with LDA by leveraging multi-omics data, highlighting that the gut microbe may be involved in the regulation of lipolysis and insulin resistance by modulating the amino acid composition.

The present study aims to evaluate the alterations in gut microbiome and plasma metabolites of dairy calves with β-glucan (BG) supplementation. Fourteen healthy newborn dairy calves with similar body weight were randomly divided into control (n = 7) and BG (n = 7) groups. All the calves were fed on the basal diet, while calves in the BG group were supplemented with oat BG on d 8 for 14 days. Serum markers, fecal microbiome, and plasma metabolites at d 21 were analyzed. The calves were weaned on d 60 and weighed. The mean weaning weight of the BG group was 4.29 kg heavier than that of the control group. Compared with the control group, the levels of serum globulin, albumin, and superoxide dismutase were increased in the BG group. Oat BG intake increased the gut microbiota richness and decreased the Firmicutes-to-Bacteroidetes ratio. Changes in serum markers were found to be correlated with the plasma metabolites, including sphingosine, trehalose, and 3-methoxy-4-hydroxyphenylglycol sulfate, and gut microbiota such as Ruminococcaceae_NK4A214, Alistipes, and Bacteroides. Overall, these results suggest that the BG promotes growth and health of pre-weaning dairy calves by affecting the interaction between the host and gut microbiota.

The effect of the Astragalus membranaceus root (AMR) on the serum metabolic profiles of preweaning calf were investigated in this study. Sixteen preweaning Holstein calves were randomly allocated into two groups with eight calves per group, and offered a control basal diet (CON group) or supplemented with 20 g superfine powder of AMR (AMR group) for 14 d. Serum samples were collected from calves on day 0, 7 and 14. Serum albumin, globulin, total protein, glucose, reduced glutathione and superoxide dismutase were evaluated. Serum metabolic profiling was analyzed using ultra-high-performance liquid chromatography-time-of-flight mass spectrometry. The results demonstrated that there were no significantly difference of total protein, glucose, reduced glu-tathione and superoxide dismutase between the CON group and AMR group (p > 0.05), while within the CON group and AMR group, serum glucose showed a continuous upward trend from 0 d to 14 d (p < 0.001). Untargeted metabolomics analysis found the metabolism of preweaning calf was considerably changed during growth, mainly including amino acid metabolism and carbohydrate metabolism and showed an increasing in protein synthesis and gluconeogenesis. 19 differential metabolites have been screened after supplementing AMR for 14 d, nine of which were up-regulated, including ornithine, L-pyroglutamic acid, L-proline and D-proline, and 10 down-regulated , containing L-kynurenine, 5-hydroxyindoleacetate, linoleic acid and 4-pyridoxic acid. Pathway analysis found these metabolites mainly participated in three primary pathways: arginine and proline metabolism, tryptophan metabolism and glutathione metabolism (p < 0.05), while linoleic acid metabolism and vitamin B6 metabolism were also enriched (0.1 < p < 0.05). Such metabolic changes reflected the enhancement of the antioxidant and anti-inflammatory capacity of prewean-ing calves.

Prepartum exercise (PA) has been proposed as a strategy for the peripartum management of dairy cows; however, the mechanism by which PA affects metabolism has not been elucidated. Here, we investigated the metabolic changes in transition dairy cows with PA. Holstein transition multiparous dairy cows were assigned to an exercise (n = 12) or a control (n = 12) group; the cows in the exercise group walked for a targeted 45 min at 3.25 km/h, two times a day. Plasma non-esterified fatty acid (NEFA), β-hydroxybutyric acid (BHBA), glucose, and triglyceride levels were measured, and metabolic profiles were analyzed using untargeted mass spectrometry. Compared with those in the control group, the concentrations of NEFA at −7 d, glucose at 0 d, and BHBA at +7 d relative to calving were considerably decreased in the exercise group. Untargeted metabolomics analysis revealed differences in the levels of key metabolites, including kynurenine, tryptophan, homovanillic acid, dopamine, cis-9-palmitoleic acid, and palmitic acid, between the exercise and control group cows. This study suggests that PA may decrease homovanillic acid and cis-9-palmitoleic acid levels and increase tryptophan levels to alleviate the metabolic stress in dairy cows during calving, thereby improving postpartum health.