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

Abstract

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

Maternal N-Acetylcysteine Therapy Prevents Hypertension in Spontaneously Hypertensive Rat Offspring: Implications of Hydrogen Sulfide-Generating Pathway and Gut Microbiota

“…Like Lactobacillus, Akkermansia is currently considered to be a beneficial microbe [42]. Our previous study reported that probiotic or prebiotic therapy that protected adult offspring against hypertension programmed by maternal high-fructose diet was related to increases of the abundance of Akkermansia [46]. Given that NAC increased fecal H 2 S levels, additional studies are required to clarify whether this discrepancy is a compensatory reduction of sulfur-metabolizing Akkermansia abundance in response to excessive colonic H 2 S. Although gut-derived H 2 S has been proposed for producing a systemic effect on BP [13], according to our data the protective effect of NAC on hypertension is mainly attributed to SOB and thiosulfate.…”

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

“…These findings suggested colonization of the mammalian GIT begins during the birthing process, with the fetus exposed in utero to maternal and environmental microbiota following cervical dilation and rupture of amniotic membranes. Similar to neonatal calves (Malmuthuge, 2016; Malmuthuge et al, 2019), the microbiome in the small intestine of newborn lambs was dominated by Proteobacteria with a transition to Firmicutes with increasing age and exposure to ingesta. Massilia (phylum Proteobacteria ) was one of the abundant bacterial genera observed in the small intestine of newborn lambs, including both the adjacent intact small intestine and the surgically isolated intestinal segments (Supplementary Figure 1A).…”

“…A correlation-based hierarchical clustering approach (Malmuthuge et al, 2019) was used to explore similarities or dissimilarities of the total bacterial communities profiled from three intestinal segments. First, a Spearman rank correlation analysis was performed using the cor() function in R to obtain correlation (ρ) between each pair of small intestinal microbial profiles based on the relative abundance of OTUs clustered at 97% similarity.…”

Seasonal Variation in Gut Microbiota Composition: Comparative Analysis of Siberian Musk Deer (Moschus moschiferus) and Forest Musk Deer (Moschus berezovskii)

“…The seasonal variations in microbiome composition in our study are likely due to seasonal changes in diets. Diet is an important factor that shapes gut microbial communities [36][37][38]. Speci cally, the ratio of ber to carbohydrates in diets can impact microbiome composition in ruminants [39].…”