Invited review: Impact of maternal health and nutrition on the microbiome and immune development of neonatal calves.

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.

accelerates intestinal microbiota maturation and is correlated with increased secretory IgA production in neonatal dairy calves.

Neonatal calves have a limited capacity to initiate immune responses due to a relatively immature adaptive immune system, which renders them susceptible to many on-farm diseases. At birth, the mucosal surfaces of the intestine are rapidly colonized by microbes in a process that promotes mucosal immunity and primes the development of the adaptive immune system. In a companion study, our group demonstrated that supplementation of a live yeast probiotic, (SCB) CNCM I-1079, to calves from birth to 1 week of age stimulates secretory IgA (sIgA) production in the intestine.

Microbial Interventions to Improve Neonatal Gut Health.

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.

Gut microbiome is linked to functions of peripheral immune cells in transition cows during excessive lipolysis.

Background: Postpartum dairy cows experiencing excessive lipolysis are prone to severe immunosuppression. Despite the extensive understanding of the gut microbial regulation of host immunity and metabolism, its role during excessive lipolysis in cows is largely unknown. Herein, we investigated the potential links between the gut microbiome and postpartum immunosuppression in periparturient dairy cows with excessive lipolysis using single immune cell transcriptome, 16S amplicon sequencing, metagenomics, and targeted metabolomics.

Childhood body mass index and associations with infant gut metabolites and secretory IgA: findings from a prospective cohort study.

Background/objectives: Differences in gut microbiota, metabolites and immune markers have been observed between individuals with and without obesity. Our study determined the temporal association between infant fecal gut metabolites, sIgA and body mass index (BMI) z score of preschool children, independent of pre/postnatal factors.

Subjects/methods: The study includes a subset of 647 infants from the CHILD Cohort Study (recruited between January 1, 2009, and December 31, 2012).

Effect of maternal separation and transportation stress on the bovine upper respiratory tract microbiome and the immune response to resident opportunistic pathogens.

Background: The bovine upper respiratory tract (URT) microbiome includes opportunistic pathogens that cause respiratory disease and stress associated with maternal separation and transportation contributes to the severity of this respiratory disease. Stress is known to alter the gut microbiome but little is known regarding the effect of stress on the URT microbiota. This study used six-month old suckling beef calves to investigate whether maternal separation (weaned), by itself or combined with transportation (weaned + transport), altered the URT microbiome and host immune responses to resident opportunistic pathogens.

Noncoding RNAs: Regulatory Molecules of Host-Microbiome Crosstalk.

Recent emerging evidence has revealed that regulatory noncoding RNAs (microRNAs, circular RNAs) modulate host-microbe interactions and they have been proposed as potential biomarkers of the host's response to microbiome-linked pathologies such as cancers, obesity, and neurodegenerative diseases. Interactions between microRNAs and circular RNAs, however, increase the complexity of the mechanisms that modulate host-microbe interactions. Current knowledge on these noncoding RNAs (ncRNAs) is mainly generated from well controlled germ-free or knockout (small) animal models.

Regulation of rumen development in neonatal ruminants through microbial metagenomes and host transcriptomes.

Background: In ruminants, early rumen development is vital for efficient fermentation that converts plant materials to human edible food such as milk and meat. Here, we investigate the extent and functional basis of host-microbial interactions regulating rumen development during the first 6 weeks of life.

Results: The use of microbial metagenomics, together with quantification of volatile fatty acids (VFAs) and qPCR, reveals the colonization of an active bacterial community in the rumen at birth.

A Novel Animal Model for Regional Microbial Dysbiosis of the Pioneer Microbial Community.

Pioneer microbiota colonizing the newborn gastrointestinal tract has long-lasting effects on host health. Restoration of the gut microbial community, following dysbiosis during the neonatal period, may be one strategy to prevent undesirable health outcomes linked to an altered neonatal gut microbiome. Without appropriate animal models that recreate the prolonged human neonatal developmental period it is not possible to effectively analyze interventions designed to restore regional microbial populations.

Taxonomic and Functional Compositions of the Small Intestinal Microbiome in Neonatal Calves Provide a Framework for Understanding Early Life Gut Health.

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 or Among the clustered microbiomes, -dominant ileal microbiomes had significantly lower abundances of , , , , and compared to the -dominated ileal microbiomes.

Colostrum feeding shapes the hindgut microbiota of dairy calves during the first 12 h of life.

This study evaluated the effect of feeding non-heated and heated colostrum on the mucosa- and digesta-associated microbiota in the colon of dairy calves during the first 12 h of life. Thirty-two neonatal Holstein male calves were fed: no colostrum (NC, n = 8), non-heated colostrum (FC, n = 12) and heated colostrum (HC (60 °C, 60 min), n = 12) immediately after birth. The abundances of mucosa- and digesta-associated total bacteria were higher in the colon of FC fed calves compared to those fed no colostrum (NC) at 12 h of life.

Fetal environment and fetal intestine are sterile during the third trimester of pregnancy.

Recent next generation sequencing studies on host-associated microbiomes generated debatable conclusions regarding the central dogma of fetal gut sterility. These observations challenge the concepts that microbial colonization of the gut begins during and after birth as well as the concept of antigen-independent prenatal maturation of mucosal-associated lymphoid tissue in ruminants and humans. The placental barrier varies markedly among mammalian species with mice and humans having haemochorial placentas (fetal tissue in direct contact with maternal blood) versus epitheliochorial placentation (maternal and fetal blood separated by six tissue layers) in ruminants.

Shift of hindgut microbiota and microbial short chain fatty acids profiles in dairy calves from birth to pre-weaning.

This study aimed to characterize mucosa- and digesta-associated microbiota in the hindgut (cecum, colon and rectum) of newborn (NB, n = 6), day 7 (n = 6), day 21 (n = 6) and day 42 (n = 6) Holstein bull calves using amplicon sequencing. The hindgut microbiota was diverse at birth, and mucosa-attached microbial community had higher individual variation than that of digesta-associated community. In total, 16 phyla were identified with Firmicutes, Bacteroidetes and Proteobacteria being the dominant microbial taxa in the hindgut.

Development and Function of the Mucosal Immune System in the Upper Respiratory Tract of Neonatal Calves.

Respiratory infections remain the second most common cause of clinical disease and mortality in newborn calves, which has led to increased interest in using vaccines early in life to mitigate this risk. Intranasal vaccination of neonatal calves can be an effective strategy to circumvent vaccine interference by maternal antibody, but this raises questions regarding onset of immune competence in the upper respiratory tract (URT) following birth. Little is known, however, about the development and function of mucosa-associated lymphoid tissue (MALT) in the URT of newborn calves and what factors, including the commensal microbiome, contribute to this early development.

Short communication: The effect of heat treatment of bovine colostrum on the concentration of oligosaccharides in colostrum and in the intestine of neonatal male Holstein calves.

The objective of this study was to determine the effect of the heat treatment (HT, 60°C for 60 min) on the concentration of bovine colostrum oligosaccharides (bCO) in pooled bovine colostrum and the intestine of neonatal male Holstein calves after feeding. First-milking colostrum was pooled from both primiparous and multiparous cows, and half of the pooled colostrum was heat-treated at 60°C for 60 min (HC), whereas the other half was not heat-treated and remained fresh (FC). At birth, 32 male Holstein calves were randomly assigned to 1 of 3 treatment groups: (1) control calves that did not receive colostrum for the duration of the experiment and were euthanized at 6 h (NC, n = 4) or 12 h (NC, n = 4), (2) calves fed fresh colostrum (FC) and were euthanized at 6 h (FC, n = 6) or 12 h (FC, n = 6), or (3) calves fed heat-treated colostrum (HC) and euthanized at 6 h (HC, n = 6) or 12 h (HC, n = 6).

Understanding the gut microbiome of dairy calves: Opportunities to improve early-life gut health.

Early gut microbiota plays a vital role in the long-term health of the host. However, understanding of these microbiota is very limited in livestock species, especially in dairy calves. Neonatal calves are highly susceptible to enteric infections, one of the major causes of calf death, so approaches to improving gut health and overall calf health are needed.

Understanding host-microbial interactions in rumen: searching the best opportunity for microbiota manipulation.

Ruminants utilize a wide variety of dietary substrates that are not digestible by the mammals, through microbial fermentation taking place in the rumen. Recent advanced molecular based approaches have allowed the characterization of rumen microbiota and its compositional changes under various treatment conditions. However, the knowledge is still limited on the impacts of variations in the rumen microbiota on host biology and function.

Transcriptome analysis reveals regional and temporal differences in mucosal immune system development in the small intestine of neonatal calves.

Background: Postnatal development of the mammalian mucosal immune system is crucial for responding to the rapid colonization by commensal bacteria and possible exposure to pathogens. This study analyzed expression patterns for mRNAs and their relationship with microRNAs (miRNAs) in the bovine small intestine during the critical neonatal period (0 to 42 days). This analysis revealed molecular mechanisms regulating the postnatal development of the intestinal mucosal immune system.

The Gut Microbiome and Its Potential Role in the Development and Function of Newborn Calf Gastrointestinal Tract.

A diverse microbial population colonizes the sterile mammalian gastrointestinal tract during and after the birth. There is increasing evidence that this complex microbiome plays a crucial role in the development of the mucosal immune system and influences newborn health. Microbial colonization is a complex process influenced by a two-way interaction between host and microbes and a variety of external factors, including maternal microbiota, birth process, diet, and antibiotics.

Heat-treated colostrum feeding promotes beneficial bacteria colonization in the small intestine of neonatal calves.

The present study investigated the effect of heat-treated colostrum feeding on the bacterial colonization in calf small intestine of neonatal calves within the first 12h of life. Newborn Holstein bull calves (n=32) were assigned to 3 treatment groups and fed with either fresh colostrum (FC, n=12) or heat-treated (60°C, 60 min) colostrum (HC, n=12) soon after birth, whereas the control (NC, n=8) group did not receive colostrum or water. Small intestinal tissues and contents were collected from proximal jejunum, distal jejunum, and ileum at 6 and 12h after birth, following euthanasia.

Model systems to analyze the role of miRNAs and commensal microflora in bovine mucosal immune system development.

Information is rapidly accumulating regarding the role of miRNAs as key regulators of immune system development and function. It is also increasingly evident that miRNAs play an important role in host-pathogen interactions through regulation of both innate and acquired immune responses. Little is known, however, about the specific role of miRNAs in regulating normal development of the mucosal immune system, especially during the neonatal period.

Potential regulatory role of microRNAs in the development of bovine gastrointestinal tract during early life.

This study aimed to investigate the potential regulatory role of miRNAs in the development of gastrointestinal tract (GIT) during the early life of dairy calves. Rumen and small intestinal (mid-jejunum and ileum) tissue samples were collected from newborn (30 min after birth; n = 3), 7-day-old (n = 6), 21-day-old (n = 6), and 42-day-old (n = 6) dairy calves. The miRNA profiling was performed using Illumina RNA-sequencing and the temporal and regional differentially expressed miRNAs were further validated using qRT-PCR.

Taxonomic identification of commensal bacteria associated with the mucosa and digesta throughout the gastrointestinal tracts of preweaned calves.

Bacterial colonization in the gastrointestinal tracts (GIT) of preweaned calves is very important, since it can influence early development and postweaning performance and health. This study investigated the composition of the bacteria along the GIT (rumen, jejunum, ileum, cecum, and colon) of preweaned bull calves (3 weeks old) using pyrosequencing to understand the segregation of bacteria between the mucosal surface and digesta. Phylogenetic analysis revealed that a total of 83 genera belonging to 13 phyla were distributed throughout the GIT of preweaned calves, with the Firmicutes, Bacteroidetes, and Proteobacteria predominating.