Multiomics analysis revealed that the metabolite profile of raw milk is associated with lactation stage of dairy cows and could be affected by variations in the ruminal microbiota.

The nutritional components and quality of milk are influenced by the rumen microbiota and its metabolites at different lactation stages. Hence, rumen fluid and milk samples from 6 dairy cows fed the same diet were collected during peak, early mid- and later mid-lactation. Untargeted metabolomics and 16S rRNA sequencing were applied for analyzing milk and rumen metabolites, as well as rumen microbial composition, respectively. The levels of lipid-related metabolites, L-glutamate, glucose-1-phosphate and acetylphosphate in milk exhibited lactation-dependent attenuation. Maltol, N-acetyl-D-glucosamine, and choline, which are associated with milk flavor or coagulation properties, as well as L-valine, lansioside-A, clitocine and ginsenoside-La increased significantly in early mid- and later mid-lactation, especially in later mid-lactation. The obvious increase in rumen microbial diversities (Ace and Shannon indices) were observed in early mid-lactation compared with peak lactation. Twenty-one differential bacterial genera of the rumen were identified, with Succinivibrionaceae_UCG-001, Candidatus Saccharimonas, Fibrobacter, and SP3-e08 being significantly enriched in peak lactation. Rikenellaceae_RC9_gut_group, Eubacterium_ruminantium_group, Lachnospira, Butyrivibrio, Eubacterium_hallii_group, and Schwartzia were most significantly enriched in early mid-lactation. In comparison, only 2 bacteria (unclassified_f__Prevotellaceae and Prevotellaceae_UCG-001) were enriched in later mid-lactation. For rumen metabolites, LPE(16:0), L-glutamate and L-tyrosine had higher levels in peak lactation, whereas PE(17:0/0:0), PE(16:0/0:0), PS(18:1(9Z)/0:0), L-phenylalanine, dulcitol, 2-(methoxymethyl)furan and 3-phenylpropyl acetate showed higher levels in early mid- and later mid-lactation. Multiomics integrated analysis revealed that a greater abundance of Fibrobacter contributed to phospholipid content in milk by increasing ruminal acetate, L-glutamate and LysoPE(16:0). Prevotellaceae_UCG-001 and unclassified_f_Prevotellaceae provide substrates for milk metabolites of the same category by increasing ruminal L-phenylalanine and dulcitol contents. These results demonstrated that milk metabolomic fingerprints and critical functional metabolites during lactation, and the key bacteria in rumen related to them. These findings provide new insights into the development of functional dairy products.

Nanopore sequencing demonstrates the roles of spermatozoal DNA N6-methyladenine in mediating transgenerational lipid metabolism disorder induced by excessive folate consumpton.

Increased consumption of folic acid is prevalent due to its beneficial effects, but growing evidence emphasizes the side effects pointing to excessive dietary folate intake. The effects of excessive paternal folic acid consumption on offspring and its transgenerational inheritance mechanism have not been elucidated. We hypothesize that excessive folic acid consumption will alter sperm DNA N6-methyladenine (6mA) and 5-methylcytosine (5mC) methylation and heritably influence offspring metabolic homeostasis. Here, we fed roosters either folic acid-control or folic acid-excess diet throughout life. Paternal chronic folic acid excessive supplementation increased hepatic lipogenesis and lipid accumulation but reduced lipolysis both in the roosters and their offspring, which was further confirmed to be induced by one-carbon metabolism inhibition and gene expression alteration associated with the Peroxisome proliferator-activated receptor pathway. Based on the spermatozoal genome-wide DNA methylome identified by Nanopore sequencing, multi-omics association analysis of spermatozoal and hepatic DNA methylome, transcriptome, and metabolome suggested that differential spermatozoal DNA 6mA and 5mC methylation could be involved in regulating lipid metabolism-related gene expression in offspring chickens. This model suggests that sperm DNA N6-methyladenine and 5-methylcytosine methylation were involved in epigenetic transmission and that paternal dietary excess folic acid leads to hepatic lipid accumulation in offspring.

Understanding host immune responses in Clostridioides difficile infection: Implications for pathogenesis and immunotherapy.

Clostridioides difficile (C. difficile) is the predominant causative agent of nosocomial diarrhea worldwide. Infection with C. difficile occurs due to the secretion of large glycosylating toxin proteins, which can lead to toxic megacolon or mortality in susceptible hosts. A critical aspect of C. difficile's biology is its ability to persist asymptomatically within the human host. Individuals harboring asymptomatic colonization or experiencing a single episode of C. difficile infection (CDI) without recurrence exhibit heightened immune responses compared to symptomatic counterparts. The significance of these immune responses cannot be overstated, as they play critical roles in the development, progression, prognosis, and outcomes of CDI. Nonetheless, our current comprehension of the immune responses implicated in CDI remains limited. Therefore, further investigation is imperative to elucidate their underlying mechanisms. This review explores recent advancements in comprehending CDI pathogenesis and how the host immune system response influences disease progression and severity, aiming to enhance our capacity to develop immunotherapy-based treatments for CDI.

Dietary fat and carbohydrate-balancing the lactation performance and methane emissions in the dairy cow industry: A meta-analysis.

For the agroecosystems of the dairy cow industry, dietary carbohydrate (starch, neutral detergent fiber [NDF]) and fat could directly affect rumen methane emissions and host energy utilization. However, the relationships among diet, lactation performance, and methane emissions need to be further determined to assist dairy farms to adjust diet formulations and feeding strategies for environmental and production management. A meta-analysis was conducted in the current study to explore quantitative patterns of dietary fat and carbohydrate at different levels in balancing lactation performance and environment sustainability of dairy cows, and to establish a methane emission prediction model using the artificial neural network (ANN) model. The results showed that the regression relationship between dietary fat, carbohydrate and methane emissions could be shown by the following models: methane = 106.78 + (14.86 × DMI), R2 = 0.80; methane = 443.17 - (46.41 × starch/NDF), R2 = 0.76; and methane = 388.91 + (31.40 × fat) - (5.42 × fat2), R2 = 0.80. The regression relationships between dietary fat, carbohydrate and lactation performance could be shown by the following models: milk fat yield = 1.08 + (0.43 × starch/NDF) - [0.34 × (starch/NDF)2], R2 = 0.79; milk protein yield = 0.68 + (0.15 × fat) - (0.016 × fat2), R2 = 0.82. In the structural equation model, we found that when formulating dietary carbohydrates and fats, it was necessary to balance the relationship between methane emissions and lactation performance. Specifically, dietary starch/NDF was lower than 0.63 (extremum point) and dietary fat was between 2.89% and 4.69% (extremum point), it could ensure that the aim of methane emission reduction (methane emissions decrease with increasing dietary starch/NDF and fat) was achieved without losing lactation performance of dairy cows (lactation performance increase with increasing dietary starch/NDF and fat). Finally, we established the ANN model to predict methane emissions (training set: R2 = 0.62; validation set: R2 = 0.61).

Multi-omics reveal mechanisms of high enteral starch diet mediated colonic dysbiosis via microbiome-host interactions in young ruminant.

BACKGROUND: Although rumen development is crucial, hindgut undertakes a significant role in young ruminants' physiological development. High-starch diet is usually used to accelerate rumen development for young ruminants, but always leading to the enteral starch overload and hindgut dysbiosis. However, the mechanism behind remains unclear. The combination of colonic transcriptome, colonic luminal metabolome, and metagenome together with histological analysis was conducted using a goat model, with the aim to identify the potential molecular mechanisms behind the disrupted hindgut homeostasis by overload starch in young ruminants. RESULT: Compared with low enteral starch diet (LES), high enteral starch diet (HES)-fed goats had significantly higher colonic pathology scores, and serum diamine oxidase activity, and meanwhile significantly decreased colonic mucosal Mucin-2 (MUC2) protein expression and fecal scores, evidencing the HES-triggered colonic systemic inflammation. The bacterial taxa Prevotella sp. P4-67, Prevotella sp. PINT, and Bacteroides sp. CAG:927, together with fungal taxa Fusarium vanettenii, Neocallimastix californiae, Fusarium sp. AF-8, Hypoxylon sp. EC38, and Fusarium pseudograminearum, and the involved microbial immune pathways including the "T cell receptor signaling pathway" were higher in the colon of HES goats. The integrated metagenome and host transcriptome analysis revealed that these taxa were associated with enhanced pathogenic ability, antigen processing and presentation, and stimulated T helper 2 cell (TH2)-mediated cytokine secretion functions in the colon of HES goats. Further luminal metabolomics analysis showed increased relative content of chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), and decreased the relative content of hypoxanthine in colonic digesta of HES goats. These altered metabolites contributed to enhancing the expression of TH2-mediated inflammatory-related cytokine secretion including GATA Binding Protein 3 (GATA3), IL-5, and IL-13. Using the linear mixed effect model, the variation of MUC2 biosynthesis explained by the colonic bacteria, bacterial functions, fungi, fungal functions, and metabolites were 21.92, 20.76, 19.43, 12.08, and 44.22%, respectively. The variation of pathology scores explained by the colonic bacterial functions, fungal functions, and metabolites were 15.35, 17.61, and 57.06%. CONCLUSIONS: Our findings revealed that enteral starch overload can trigger interrupted hindgut host-microbiome homeostasis that led to impaired mucosal, destroyed colonic water absorption, and TH2-mediated inflammatory process. Except for the colonic metabolites mostly contribute to the impaired mucosa, the nonnegligible contribution from fungi deserves more future studies focused on the fungal functions in hindgut dysbiosis of young ruminants. Video Abstract.

Multi-omics revealed the long-term effect of ruminal keystone bacteria and the microbial metabolome on lactation performance in adult dairy goats.

BACKGROUND: The increased growth rate of young animals can lead to higher lactation performance in adult goats; however, the effects of the ruminal microbiome on the growth of young goats, and the contribution of the early-life rumen microbiome to lifelong growth and lactation performance in goats has not yet been well defined. Hence, this study assessed the rumen microbiome in young goats with different average daily gains (ADG) and evaluated its contribution to growth and lactation performance during the first lactation period. RESULTS: Based on monitoring of a cohort of 99 goats from youth to first lactation, the 15 highest ADG (HADG) goats and 15 lowest ADG (LADG) goats were subjected to rumen fluid microbiome and metabolome profiling. The comparison of the rumen metagenome of HADG and LADG goats revealed that ruminal carbohydrate metabolism and amino acid metabolism function were enhanced in HADG goats, suggesting that the rumen fluid microbiome of HADG goats has higher feed fermentation ability. Co-occurrence network and correlation analysis revealed that Streptococcus, Candidatus Saccharimonans, and Succinivibrionaceae UCG-001 were significantly positively correlated with young goats' growth rates and some HADG-enriched carbohydrate and protein metabolites, such as propionate, butyrate, maltoriose, and amino acids, while several genera and species of Prevotella and Methanogens exhibited a negative relationship with young goats' growth rates and correlated with LADG-enriched metabolites, such as rumen acetate as well as methane. Additionally, some functional keystone bacterial taxa, such as Prevotella, in the rumen of young goats were significantly correlated with the same taxa in the rumen of adult lactation goats. Prevotella also enriched the rumen of LADG lactating goats and had a negative effect on rumen fermentation efficiency in lactating goats. Additional analysis using random forest machine learning showed that rumen fluid microbiota and their metabolites of young goats, such as Prevotellaceae UCG-003, acetate to propionate ratio could be potential microbial markers that can potentially classify high or low ADG goats with an accuracy of prediction of > 81.3%. Similarly, the abundance of Streptococcus in the rumen of young goats could be predictive of milk yield in adult goats with high accuracy (area under the curve 91.7%). CONCLUSIONS: This study identified the keystone bacterial taxa that influence carbohydrate and amino acid metabolic functions and shape the rumen fluid microbiota in the rumen of adult animals. Keystone bacteria and their effects on rumen fluid microbiota and metabolome composition during early life can lead to higher lactation performance in adult ruminants. These findings suggest that the rumen microbiome together with their metabolites in young ruminants have long-term effect on feed efficiency and animal performance. The fundamental knowledge may allow us to develop advanced methods to manipulate the rumen microbiome and improve production efficiency of ruminants. Video Abstract.

Multi-omics reveals that the host-microbiome metabolism crosstalk of differential rumen bacterial enterotypes can regulate the milk protein synthesis of dairy cows.

BACKGROUND: Dairy cows' lactation performance is the outcome of the crosstalk between ruminal microbial metabolism and host metabolism. However, it is still unclear to what extent the rumen microbiome and its metabolites, as well as the host metabolism, contribute to regulating the milk protein yield (MPY). METHODS: The rumen fluid, serum and milk of 12 Holstein cows with the same diet (45% coarseness ratio), parity (2-3 fetuses) and lactation days (120-150 d) were used for the microbiome and metabolome analysis. Rumen metabolism (rumen metabolome) and host metabolism (blood and milk metabolome) were connected using a weighted gene co-expression network (WGCNA) and the structural equation model (SEM) analyses. RESULTS: Two different ruminal enterotypes, with abundant Prevotella and Ruminococcus, were identified as type1 and type2. Of these, a higher MPY was found in cows with ruminal type2. Interestingly, [Ruminococcus] gauvreauii group and norank_f_Ruminococcaceae (the differential bacteria) were the hub genera of the network. In addition, differential ruminal, serum and milk metabolome between enterotypes were identified, where the cows with type2 had higher L-tyrosine of rumen, ornithine and L-tryptophan of serum, and tetrahydroneopterin, palmitoyl-L-carnitine, S-lactoylglutathione of milk, which could provide more energy and substrate for MPY. Further, based on the identified modules of ruminal microbiome, as well as ruminal serum and milk metabolome using WGCNA, the SEM analysis indicated that the key ruminal microbial module1, which contains the hub genera of the network ([Ruminococcus] gauvreauii group and norank_f_Ruminococcaceae) and high abundance of bacteria (Prevotella and Ruminococcus), could regulate the MPY by module7 of rumen, module2 of blood, and module7 of milk, which contained L-tyrosine and L-tryptophan. Therefore, in order to more clearly reveal the process of rumen bacterial regulation of MPY, we established the path of SEM based on the L-tyrosine, L-tryptophan and related components. The SEM based on the metabolites suggested that [Ruminococcus] gauvreauii group could inhibit the energy supply of serum tryptophan to MPY by milk S-lactoylglutathione, which could enhance pyruvate metabolism. Norank_f_Ruminococcaceae could increase the ruminal L-tyrosine, which could provide the substrate for MPY. CONCLUSION: Our results indicated that the represented enterotype genera of Prevotella and Ruminococcus, and the hub genera of [Ruminococcus] gauvreauii group and norank_f_Ruminococcaceae could regulate milk protein synthesis by affecting the ruminal L-tyrosine and L-tryptophan. Moreover, the combined analysis of enterotype, WGCNA and SEM could be used to connect rumen microbial metabolism with host metabolism, which provides a fundamental understanding of the crosstalk between host and microorganisms in regulating the synthesis of milk composition.

Beyond faecal microbiota transplantation, the non-negligible role of faecal virome or bacteriophage transplantation.

Intestinal microbiota, which contains bacteria, archaea, fungi, protists, and viruses including bacteriophages, is symbiotic and evolves together with humans. The balanced intestinal microbiota plays indispensable roles in maintaining and regulating host metabolism and health. Dysbiosis has been associated with not only intestinal diseases but other diseases such as neurology disorders and cancers. Faecal microbiota transplantation (FMT) or faecal virome or bacteriophage transplantation (FVT or FBT), transfers faecal bacteria or viruses, with a focus on bacteriophage, from one healthy individual to another individual (normally unhealthy condition), and aims to restore the balanced gut microbiota and assist in subduing diseases. In this review, we summarized the applications of FMT and FVT in clinical settings, discussed the advantages and challenges of FMT and FVT currently and proposed several considerations prospectively. We further provided our understanding of why FMT and FVT have their limitations and raised the possible future development strategy of FMT and FVT.

Pharmacological vitamin C inhibits mTOR signaling and tumor growth by degrading Rictor and inducing HMOX1 expression.

Pharmacological vitamin C (VC) is a potential natural compound for cancer treatment. However, the mechanism underlying its antitumor effects remains unclear. In this study, we found that pharmacological VC significantly inhibits the mTOR (including mTORC1 and mTORC2) pathway activation and promotes GSK3-FBXW7-mediated Rictor ubiquitination and degradation by increasing the cellular ROS. Moreover, we identified that HMOX1 is a checkpoint for pharmacological-VC-mediated mTOR inactivation, and the deletion of FBXW7 or HMOX1 suppresses the regulation of pharmacological VC on mTOR activation, cell size, cell viability, and autophagy. More importantly, it was observed that the inhibition of mTOR by pharmacological VC supplementation in vivo produces positive therapeutic responses in tumor growth, while HMOX1 deficiency rescues the inhibitory effect of pharmacological VC on tumor growth. These results demonstrate that VC influences cellular activities and tumor growth by inhibiting the mTOR pathway through Rictor and HMOX1, which may have therapeutic potential for cancer treatment.

Metagenomic and single-cell RNA-Seq survey of the Helicobacter pylori-infected stomach in asymptomatic individuals.

Helicobacter pylori colonization of the gastric niche can persist for years in asymptomatic individuals. To deeply characterize the host-microbiota environment in H. pylori-infected (HPI) stomachs, we collected human gastric tissues and performed metagenomic sequencing, single-cell RNA-Seq (scRNA-Seq), flow cytometry, and fluorescent microscopy. HPI asymptomatic individuals had dramatic changes in the composition of gastric microbiome and immune cells compared with noninfected individuals. Metagenomic analysis uncovered pathway alterations related to metabolism and immune response. scRNA-Seq and flow cytometry data revealed that, in contrast to murine stomachs, ILC2s are virtually absent in the human gastric mucosa, whereas ILC3s are the dominant population. Specifically, proportion of NKp44+ ILC3s out of total ILCs were highly increased in the gastric mucosa of asymptomatic HPI individuals, and correlated with the abundance of selected microbial taxa. In addition, CD11c+ myeloid cells and activated CD4+ T cells and B cells were expanded in HPI individuals. B cells of HPI individuals acquired an activated phenotype and progressed into a highly proliferating germinal-center stage and plasmablast maturation, which correlated with the presence of tertiary lymphoid structures within the gastric lamina propria. Our study provides a comprehensive atlas of the gastric mucosa-associated microbiome and immune cell landscape when comparing asymptomatic HPI and uninfected individuals.

Promotion of intestinal epithelial cell apoptosis by enterotoxigenic Escherichia coli via PKA-mediated inhibition of mTORC1 activation.

Enterotoxigenic Escherichia coli (ETEC) is the main causative pathogen of diarrhea. It causes acute watery diarrhea that leads to rapid dehydration and prostration within hours. ETEC is still an important cause of neonatal and post-weaning diarrhea in pigs. However, the mechanism underlying ETEC-induced diarrhea is not yet clear. In this study, we investigated these mechanisms and found that the mTORC1 pathway plays a role in the host response to ETEC F4 infection. Specifically, we found that ETEC F4 treatment significantly repressed mTORC1 activity as well as cell proliferation, promoted apoptosis and regulated the expression of diarrhea-related genes via the promotion of PKA-mediated phosphorylation of SIN1, which plays a critical role in the assembly of mTORC2. These findings indicate that PKA is a checkpoint for ETEC-induced diarrhea. In terms of potential therapeutic strategies, we found that ZnSO4 dramatically rescued ETEC F4-induced the inhibition of mTORC1 activity and cell viability and the induction of apoptosis and alterations in the expression of diarrhea-related genes. Thus, the present findings demonstrate that ETEC F4 influences mTORC1 activation by inhibiting the assembly of mTORC2 through PKA-mediated phosphorylation of SIN1. Further, supplementation with ZnSO4 is an effective strategy for blocking the effect of ETEC F4 on mTORC1 activation, and it may have potential clinical applications in the treatment of ETEC F4-induced diarrhea.

Farnesoid X Receptor (FXR) Regulates mTORC1 Signaling and Autophagy by Inhibiting SESN2 Expression.

SCOPE: The mechanistic target of rapamycin complex 1 (mTORC1), as a link between nutrients and autophagy, senses many nutrients in the microenvironment. A growing body of recent literature describes the function of bile acids (BAs) as versatile signaling molecules, while it remains largely unclear whether mTORC1 can sense BAs and the mechanism has not been studied. METHODS AND RESULTS: After treating LO2 cells with indicated concentration of chenodeoxycholic acid (CDCA) and farnesoid X receptor (FXR) inhibitor/activator for 6 h, it finds that CDCA and FXR significantly accelerate mTORC1 activation. The results of immunofluorescence indicate that CDCA and FXR inhibit cellular autophagy through activating mTORC1 pathway. In particular, these findings show that CDCA and FXR promote the lysosomal translocation and activation of mTORC1 in an amino acid-sensitive manner. Mechanistically, the transcriptomics data indicate that SESN2 is a checkpoint for mTORC1 lysosome translocation and activation induced by FXR, and knockdown SESN2 with siRNA suppresses the regulation of FXR on autophagy. CONCLUSION: These results indicate that FXR-induced decrease in SESN2 expression and activation of the mTORC1 pathway can control autophagy and be explored as potential therapeutic targets for enterohepatic and metabolic disorders.

The salivary microbiota is altered in cervical dysplasia patients and influenced by conization.

This study supports the correlation between the salivary microbiota and cervical dysplasia and suggests that smoking influences the salivary microbiota.

An overview of host-derived molecules that interact with gut microbiota.

The gut microbiota comprises bacteria, archaea, fungi, protists, and viruses that live together and interact with each other and with host cells. A stable gut microbiota is vital for regulating host metabolism and maintaining body health, while a disturbed microbiota may induce different kinds of disease. In addition, diet is also considered to be the main factor that influences the gut microbiota. The host could shape the gut microbiota through other factors. Here, we reviewed the mechanisms that mediate host regulation on gut microbiota, involved in gut-derived molecules, including gut-derived immune system molecules (secretory immunoglobulin A, antimicrobial peptides, cytokines, cluster of differentiation 4+ effector T cell, and innate lymphoid cells), sources related to gut-derived mucosal molecules (carbon sources, nitrogen sources, oxygen sources, and electron respiratory acceptors), gut-derived exosomal noncoding RNA (ncRNAs) (microRNAs, circular RNA, and long ncRNA), and molecules derived from organs other than the gut (estrogen, androgen, neurohormones, bile acid, and lactic acid). This study provides a systemic overview for understanding the interplay between gut microbiota and host, a comprehensive source for potential ways to manipulate gut microbiota, and a solid foundation for future personalized treatment that utilizes gut microbiota.

The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1α.

Cattle can efficiently perform de novo generation of glucose through hepatic gluconeogenesis to meet post-weaning glucose demand. Substantial evidence points to cattle and non-ruminant animals being characterized by phylogenetic features in terms of their differing capacity for hepatic gluconeogenesis, a process that is highly efficient in cattle yet the underlying mechanism remains unclear. Here we used a variety of transcriptome data, as well as tissue and cell-based methods to uncover the mechanisms of high-efficiency hepatic gluconeogenesis in cattle. We showed that cattle can efficiently convert propionate into pyruvate, at least partly, via high expression of acyl-CoA synthetase short-chain family member 1 (ACSS1), propionyl-CoA carboxylase alpha chain (PCCA), methylmalonyl-CoA epimerase (MCEE), methylmalonyl-CoA mutase (MMUT), and succinate-CoA ligase (SUCLG2) genes in the liver (P < 0.01). Moreover, higher expression of the rate-limiting enzymes of gluconeogenesis, such as phosphoenolpyruvate carboxykinase (PCK) and fructose 1,6-bisphosphatase (FBP), ensures the efficient operation of hepatic gluconeogenesis in cattle (P < 0.01). Mechanistically, we found that cattle liver exhibits highly active mechanistic target of rapamycin complex 1 (mTORC1), and the expressions of PCCA, MMUT, SUCLG2, PCK, and FBP genes are regulated by the activation of mTORC1 (P < 0.001). Finally, our results showed that mTORC1 promotes hepatic gluconeogenesis in a peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) dependent manner. Collectively, our results not only revealed an important mechanism responsible for the quantitative differences in the efficiency of hepatic gluconeogenesis in cattle versus non-ruminant animals, but also established that mTORC1 is indeed involved in the regulation of hepatic gluconeogenesis through PGC-1α. These results provide a novel potential insight into promoting hepatic gluconeogenesis through activated mTORC1 in both ruminants and mammals.

Paternal transgenerational nutritional epigenetic effect: A new insight into nutritional manipulation to reduce the use of antibiotics in animal feeding.

The use of antibiotics in animal feeding has been banned in many countries because of increasing concerns about the development of bacterial resistance to antibiotics and potential issues on food safety. Searching for antibiotic substitutes is essential. Applying transgenerational epigenetic technology to animal production could be an alternative. Some environmental changes can be transferred to memory-like responses in the offspring through epigenetic mechanisms without changing the DNA sequence. In this paper, we reviewed those nutrients and non-nutritional additives that have transgenerational epigenetic effects, including some amino acids, vitamins, and polysaccharides. The paternal transgenerational nutritional epigenetic regulation was particularly focused on mechanism of the substantial contribution of male stud animals to the animal industries. We illustrated the effects of paternal transgenerational epigenetics on the metabolism and immunity in farming animals and proposed strategies to modulate male breeding livestock or poultry.

Ruminal Microbiota Determines the High-Fiber Utilization of Ruminants: Evidence from the Ruminal Microbiota Transplant.

The rumen, which contains a series of prokaryotes and eukaryotes with high abundance, determines the high ability to degrade complex carbohydrates in ruminants. Using 16S rRNA gene sequencing, we compared the ruminal microbiota of dairy goats with that in the foregut and colon of mice and found more Bacteroides identified in the rumen, which helps ruminants to utilize plant-derived polysaccharides, cellulose, and other structural carbohydrates. Furthermore, high-fiber diets did not significantly increase intestinal fiber-degrading bacteria in mice, but did produce higher levels of ruminal fiber-degrading bacteria in dairy goats. Through rumen microbe transplantation (RMT), we found that rumen-derived fiber-degrading bacteria can colonize the intestines of mice to exert their fiber-degrading function, but their colonization efficiency is affected by diet. Additionally, the colonization of these fiber-degrading bacteria in the colon may involve higher content of butyrate in the colon, protecting the colonic epithelial barrier and promoting energy metabolism. Overall, the fiber degradation function of rumen bacteria through RMT was verified, and our results provide new insights into isolating the functional and beneficial fiber-degrading bacteria in the rumen, providing a theoretical basis for the role of dietary fiber in intestinal health. IMPORTANCE Ruminants have a powerful progastric digestive system that converts structural carbohydrates into nutrients useful to humans. It is well known that this phenomenon is due to the fact that the rumen of ruminants is a natural microbial fermenter, which can ferment structural carbohydrates such as cellulose and hemicellulose and transform them into volatile fatty acids to supply energy for host. However, monogastric animals have an inherent disadvantage in utilizing fiber, so screening rumen-derived fiber-degrading bacteria as a fermentation strain for biological feed is needed in an attempt at improving the fiber digestibility of monogastric animals. In this study, a ruminal microbiota transplant experiment from goats to mice proves that ruminal microbiota could serve as a key factor in utilization of high-fiber diets and provides a new perspective for the development of probiotics with fiber degradation function from the rumen and the importance of the use of prebiotics during the intake of probiotics.

The right bug in the right place: opportunities for bacterial vaginosis treatment.

Bacterial vaginosis (BV) is a condition in which the vaginal microbiome presents an overgrowth of obligate and facultative anaerobes, which disturbs the vaginal microbiome balance. BV is a common and recurring vaginal infection among women of reproductive age and is associated with adverse health outcomes and a decreased quality of life. The current recommended first-line treatment for BV is antibiotics, despite the high recurrence rate. Live biopharmaceutical products/probiotics and vaginal microbiome transplantation (VMT) have also been tested in clinical trials for BV. In this review, we discuss the advantages and challenges of current BV treatments and interventions. Furthermore, we provide our understanding of why current clinical trials with probiotics have had mixed results, which is mainly due to not administering the correct bacteria to the correct body site. Here, we propose a great opportunity for large clinical trials with probiotic strains isolated from the vaginal tract (e.g., Lactobacillus crispatus) and administered directly into the vagina after pretreatment.

Optimizing the growth and immune system of dairy calves by subdividing the pre-weaning period and providing different milk volumes for each stage.

In systematically considering the advantages and disadvantages of complementarity in high or low milk feeding, novel milk feeding schemes involving altering the volume of supplied milk in different stages of the pre-weaning period but maintaining the total milk feeding volume were tested. Twenty-seven newborn male Holstein calves were selected and randomly assigned to 3 treatments. Calves in the control (CON) group were fed 7 L of milk daily from 4 to 66 d of age. Calves in the low-high (LH) group were fed 6 L of milk daily at the beginning, and then the daily feeding volume was later increased to 7 to 8 L of milk, which served as the early-period low-volume feeding group. The calves in the high-low (HL) group were fed 7 to 8 L daily at the beginning, and then the daily feeding volume was decreased to 6 L of milk, which served as the early-period high-volume feeding group. Then all calves were fed 3 L of milk daily from 67 to 70 d of age, weaned at 70 d of age, and then fed starter feed to 100 d of age. All calves had access to the starter feed from 15 to 100 d of age. The diarrheal condition of calves was recorded daily and the growth performance including the starter feed intake and body weight of calves was recorded at 70 and 100 d of age. Then, five 100-d-old calves from each treatment were sampled for measurement of plasma indices, ruminal morphology, and volatile fatty acids. When compared with the CON and LH groups, calves in the HL group exhibited a significantly increased body weight and lower diarrhoeal rate. When compared with the CON group, calves in the HL group exhibited a significantly increased average daily feed intake, ruminal epithelium papillae length, total volatile fatty acids, and percentages of propionate and butyrate. Moreover, the significantly increased plasma immunoglobulin G (IgG) content and a trend of decreased tumor necrosis factor-α (TNF-α) content (P = 0.083) were also identified in the HL group when compared with the CON group. Overall, the early-period high-volume feeding for calves produced greater body weight gain and a lower incidence of diarrhea.

Real-time monitoring of ruminal microbiota reveals their roles in dairy goats during subacute ruminal acidosis.

Ruminal microbiota changes frequently with high grain diets and the occurrence of subacute ruminal acidosis (SARA). A grain-induced goat model of SARA, with durations of a significant decrease in the rumen pH value to less than 5.6 and an increase in the rumen lipopolysaccharides concentration, is constructed for real-time monitoring of bacteria alteration. Using 16 S rRNA gene sequencing, significant bacterial differences between goats from the SARA and healthy groups are identified at every hour for six continuous hours after feeding. Moreover, 29 common differential genera between two groups over 6 h after feeding are all related to the altered pH and lipopolysaccharides. Transplanting the microbiota from donor goats with SARA could induce colonic inflammation in antibiotic-pretreated mice. Overall, significant differences in the bacterial community and rumen fermentation pattern between the healthy and SARA dairy goats are real-time monitored, and then tested using ruminal microbe transplantation to antibiotic-treated mice.