Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut.

Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5(-/-) gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5(-/-) host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity-directed development of flagellin-specific adaptive immune responses can modulate the microbiome's production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis.

Long-term temporal analysis of the human fecal microbiota revealed a stable core of dominant bacterial species.

Next-generation sequencing has greatly contributed to an improved ecological understanding of the human gut microbiota. Nevertheless, questions remain regarding the characteristics of this ecosystem and the ecological processes that shape it, and controversy has arisen regarding the stability of the bacterial populations and the existence of a temporal core. In this study, we have characterized the fecal microbial communities of three human individuals over a one-year period by 454 pyrosequencing of 16S rRNA tags in order to investigate the temporal characteristics of the bacterial communities. The findings revealed a temporal core of 33 to 40 species-level Operational Taxonomic Units (OTUs) within subjects. Although these OTUs accounted only for around 12% of the total OTUs detected, they added up to >75% of the total sequences obtained for each individual. In order to determine the capacity of the sequencing and bioinformatic approaches applied during this study to accurately determine the proportion of a core microbiota, we analyzed the fecal microbiota of nine mice with a defined three-member community. This experiment revealed that the sequencing approach inflated the amount of rare OTUs, which introduced a significant degree of artificial variation across samples, and hence reduced the apparent fraction of shared OTUs. However, when assessing the data quantitatively by focusing on dominant lineages, the sequencing approaches deliver an accurate representation of the community. In conclusion, this study revealed that the human fecal microbiota is dominated by around 40 species that maintain persistent populations over the duration of one year. The findings allow conclusions about the ecological factors that shape the community and support the concept of a homeostatic ecosystem controlled largely by deterministic processes. Our analysis of a three-member community revealed that methodological artifacts of OTU-based approaches complicate core calculations, and these limitations have to be considered in the interpretation of microbiome studies.

Supplementation with aged garlic extract improves both NK and γδ-T cell function and reduces the severity of cold and flu symptoms: a randomized, double-blind, placebo-controlled nutrition intervention.

BACKGROUND & AIMS: Earlier studies show that dietary bioactive compounds can modify proliferation of γδ-T cells. Garlic contains numerous compounds that have this potential and, in addition, has been shown to influence NK cell function. Our primary aim was to demonstrate that aged garlic extract could modify these immune cells. METHODS: A randomized, double-blind, placebo-controlled parallel intervention study recruited 120 healthy subjects (60 per group) to determine the effect of aged garlic extract supplementation (2.56 g/d) on immune cell proliferation and cold and flu symptoms. RESULTS: After 45 d of consuming an encapsulated aged garlic extract, γδ-T cells (p = 0.039, n = 56) and NK cells (p = 0.043, n = 56) were shown to proliferate better compared to placebo. After 90 d of supplementation, illness diary entries showed that the incidence of colds and flu, a secondary outcome, were not statistically different; however, the group consuming the aged garlic extract appeared to have reduced severity as noted by a reduction in the number of symptoms reported (21% fewer, p < 0.001, z-test of proportions), a reduction in the number of days (61% fewer, p < 0.001, z-test) and incidences (58% fewer p < 0.001, z-test) where the subjects functioned sub-optimally and the number of work/school days missed due to illness (58% fewer, p = 0.035, z-test). CONCLUSIONS: These results suggest that supplementation of the diet with aged garlic extract may enhance immune cell function and that this may be responsible, in part, for reduced severity of colds and flu.