Overview of the rules of the microbial engagement in the gut microbiome: a step towards microbiome therapeutics.

Human gut microbiome is a diversified, resilient, immuno-stabilized, metabolically active and physiologically essential component of the human body. Scientific explorations have been made to seek in-depth information about human gut microbiome establishment, microbiome functioning, microbiome succession, factors influencing microbial community dynamics and the role of gut microbiome in health and diseases. Extensive investigations have proposed the microbiome therapeutics as a futuristic medicine for various physiological and metabolic disorders. A comprehensive outlook of microbial colonization, host-microbe interactions, microbial adaptation, commensal selection and immuno-survivability is still required to catalogue the essential genetic and physiological features for the commensal engagement. Evolution of a structured human gut microbiome relies on the microbial flexibility towards genetic, immunological and physiological adaptation in the human gut. Key features for commensalism could be utilized in developing tailor-made microbiome-based therapy to overcome various physiological and metabolic disorders. This review describes the key genetics and physiological traits required for host-microbe interaction and successful commensalism to institute a human gut microbiome.

Fecal microbiota colonization dynamics in dairy heifers associated with early-life rumen microbiota modulation and gut health.

Early-life modulation of rumen microbiota holds promise for enhancing calf growth, health, and long-term production in ruminants. However, limited attention has been given to the impact of rumen microbiota modulation on the establishment of hindgut microbiota. In this study, fecal microbiota development was examined in identical twin calves for 12 months. The treatment group (T-group) received adult cow fresh rumen liquid inoculum during the pre-weaning period, while the control group did not (C-group). The effects of inoculum were assessed on calf gut health and as microbial seeding route into the hindgut. The early rumen modulation had no effect on age-related fecal microbiota development. The fecal bacterial community evolved gradually following dietary changes and categorized into pre-weaning and post-weaning communities. Bacterial richness increased with age and stabilized at month 9, while between-sample variation reduced in post-weaning samples. Archaeal load in fecal samples increased after month 4, while archaeal richness increased and stabilized in both groups by month 9. Between-sample similarity was higher during the pre-weaning period, with increased dissimilarity from month 4 onward. Anaerobic fungi were detected in feces at month 4, with richness peaking at month 7. Before month 6, fungal community composition distinctly differed from mature communities. When colostrum, calf rumen, and donor inoculum were evaluated as seeding sources for hindgut colonization, the calf's own rumen was identified as the primary seeding source for fecal bacteria and fungi. Colostrum was a source for several bacteria detected in feces, but these were of temporary importance until weaning. The donor inoculum had limited impact on gut health as diarrhea rates were similar between the T-group and C-group. In conclusion, early-life microbiota modulation shows potential in ruminant development. However, a more targeted approach with bacteria adapted to the hindgut environment may be necessary to modulate hindgut effectively. This research contributes to our understanding of the complex relationship between gut microbiota and calf health and growth.

Long-term effects of early-life rumen microbiota modulation on dairy cow production performance and methane emissions.

Rumen microbiota modulation during the pre-weaning period has been suggested as means to affect animal performance later in life. In this follow-up study, we examined the post-weaning rumen microbiota development differences in monozygotic twin-heifers that were inoculated (T-group) or not inoculated (C-group) (n = 4 each) with fresh adult rumen liquid during their pre-weaning period. We also assessed the treatment effect on production parameters and methane emissions of cows during their 1st lactation period. The rumen microbiota was determined by the 16S rRNA gene, 18S rRNA gene, and ITS1 amplicon sequencing. Animal weight gain and rumen fermentation parameters were monitored from 2 to 12 months of age. The weight gain was not affected by treatment, but butyrate proportion was higher in T-group in month 3 (p = 0.04). Apart from archaea (p = 0.084), the richness of bacteria (p < 0.0001) and ciliate protozoa increased until month 7 (p = 0.004) and anaerobic fungi until month 11 (p = 0.005). The microbiota structure, measured as Bray-Curtis distances, continued to develop until months 3, 6, 7, and 10, in archaea, ciliate protozoa, bacteria, and anaerobic fungi, respectively (for all: p = 0.001). Treatment or age × treatment interaction had a significant (p < 0.05) effect on 18 bacterial, 2 archaeal, and 6 ciliate protozoan taxonomic groups, with differences occurring mostly before month 4 in bacteria, and month 3 in archaea and ciliate protozoa. Treatment stimulated earlier maturation of prokaryote community in T-group before month 4 and earlier maturation of ciliate protozoa at month 2 (Random Forest: 0.75 month for bacteria and 1.5 month for protozoa). No treatment effect on the maturity of anaerobic fungi was observed. The milk production and quality, feed efficiency, and methane emissions were monitored during cow's 1st lactation. The T-group had lower variation in energy-corrected milk yield (p < 0.001), tended to differ in pattern of residual energy intake over time (p = 0.069), and had numerically lower somatic cell count throughout their 1st lactation period (p = 0.081), but no differences between the groups in methane emissions (g/d, g/kg DMI, or g/kg milk) were observed. Our results demonstrated that the orally administered microbial inoculant induced transient changes in early rumen microbiome maturation. In addition, the treatment may influence the later production performance, although the mechanisms that mediate these effects need to be further explored.

Fresh Rumen Liquid Inoculant Enhances the Rumen Microbial Community Establishment in Pre-weaned Dairy Calves.

The development of the functional rumen in calves involves a complex interplay between the host and host-related microbiome. Attempts to modulate rumen microbial community establishment may therefore have an impact on weaning success, calf health, and animal performance later in life. In this experiment, we aimed to elucidate how rumen liquid inoculum from an adult cow, provided to calves during the pre-weaning period, influences the establishment of rumen bacterial, archaeal, fungal, and ciliate protozoan communities in monozygotic twin calves (n = 6 pairs). The calves were divided into treatment (T-group) and control (C-group) groups, where the T-group received fresh rumen liquid as an oral inoculum during a 2-8-week period. The C-group was not inoculated. The rumen microbial community composition was determined using bacterial and archaeal 16S ribosomal RNA (rRNA) gene, protozoal 18S rRNA gene, and fungal ITS1 region amplicon sequencing. Animal weight gain and feed intake were monitored throughout the experiment. The T-group tended to have a higher concentrate intake (Treatment: p < 0.08) and had a significantly higher weekly weight gain (Treatment: p < 0.05), but no significant difference in volatile fatty acid concentrations between the groups was observed. In the T-group, the inoculum stimulated the earlier establishment of mature rumen-related bacterial taxa, affecting significant differences between the groups until 6 weeks of age. The inoculum also increased the archaeal operational taxonomic unit (OTU) diversity (Treatment: p < 0.05) but did not affect the archaeal quantity. Archaeal communities differed significantly between groups until week 4 (p = 0.02). Due to the inoculum, ciliate protozoa were detected in the T-group in week 2, while the C-group remained defaunated until 6 weeks of age. In week 8, Eremoplastron dilobum was the dominant ciliate protozoa in the C-group and Isotricha sp. in the T-group, respectively. The Shannon diversity of rumen anaerobic fungi reduced with age (Week: p < 0.01), and community establishment was influenced by a change of diet and potential interaction with other rumen microorganisms. Our results indicate that an adult cow rumen liquid inoculum enhanced the maturation of bacterial and archaeal communities in pre-weaning calves' rumen, whereas its effect on eukaryotic communities was less clear and requires further investigation.

Establishment and Stability of the Murine Oral Microbiome.

Commensal microbiomes exert critical functions at barrier sites. In particular, establishment of the commensal microbiome after birth dictates immune functionality and tissue homeostasis at mucosal surfaces. To investigate the establishment and stability of the oral mucosal microbiome in mice, we evaluated oral microbiome communities shortly after birth, through adulthood, and up to 1 y of life in a controlled manner, using sequential oral samples from the same mice over time. We further evaluated transmissibility of oral microbiomes from parents and during cohousing experiments and evaluated susceptibility to oral inflammatory disease in mice harboring distinct microbiomes. Our work reveals basic principles in the establishment and stability of a health-associated oral microbiome after birth and provides insights that may be important for host-microbiome experimentation in animal models.

Delayed Establishment of Gut Microbiota in Infants Delivered by Cesarean Section.

The maternal vaginal microbiome is an important source for infant gut microbiome development. However, infants delivered by Cesarean section (CS) do not contact the maternal vaginal microbiome and this delivery method may perturb the early establishment and development of the gut microbiome. The aim of this study was to investigate the early gut microbiota of Korean newborns receiving the same postpartum care services for two weeks after birth by delivery mode using fecal samples collected at days 3, 7, and 14. Early gut microbiota development patterns were examined using 16S rRNA gene-based sequencing from 132 infants either born vaginally (VD, n = 64) or via Cesarean section (CS, n = 68). VD-born neonates showed increased alpha diversity in infant fecal samples collated at days 7 and 14 compared to those from day 3, while those of CS infants did not differ (p < 0.015). Bacterial structures of infants from both groups separated at day 7 (p < 0.001) and day 14 (p < 0.01). The bacterial structure of VD infants gradually changed over time (day 3 vs. day 7, p < 0.012; day 3 vs. day 14, p < 0.001). Day 14 samples of CS infants differed from day 3 and 7 samples (day 3 vs. day 14, p < 0.001). VD infant relative abundance of Bifidobacterium (days 7, 14), Bacteroides (days 7, 14), and Lachnospiraceae (day 7) significantly increased compared to CS infants, with a lower abundance of Enterobacteriaceae (found in all periods of the CS group) (LDA > 3.0). Relative abundances of Bifidobacterium, Lactobacillus, and Staphylococcus were significantly increased in both VD and CS groups at day 14 (LDA > 3.0). Predicted functional analysis showed that VD infants had overrepresented starch/sucrose, amino acid and nucleotide metabolism in gut microbiota with depleted lipopolysaccharide biosynthesis until day 14 compared to CS infants. This study confirmed that delivery mode is the major determinant of neonatal intestinal microbiome establishment and provides a profile of microbiota perturbations in CS infants. Our findings provide preliminary insight for establishing recovery methods to supply the specific microbes missing in CS infants.