To B12 or not to B12: Five questions on the role of cobalamin in host-microbial interactions

Rowley, Carol A.; Kendall, Melissa M.

doi:10.1371/journal.ppat.1007479

Cited by 73 publications

(61 citation statements)

References 23 publications

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“…Why there is an enrichment of genes involved in vitamin B 12 biosynthesis in GPA patients is not clear. Within the human gut microbiota, ~ 80% of bacteria have a requirement for vitamin B 12 , but only 20% can produce it [30], suggesting that there is significant competition for vitamin B 12 , which is likely mirrored in the nose. Indeed, certain gut bacteria have mechanisms for the capture of vitamin B 12 from host proteins [31].…”

Section: Discussionmentioning

confidence: 99%

The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study

et al. 2019

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BackgroundEar, nose and throat involvement in granulomatosis with polyangiitis (GPA) is frequently the initial disease manifestation. Previous investigations have observed a higher prevalence of Staphylococcus aureus in patients with GPA, and chronic nasal carriage has been linked with an increased risk of disease relapse. In this cross-sectional study, we investigated changes in the nasal microbiota including a detailed analysis of Staphylococcus spp. by shotgun metagenomics in patients with active and inactive granulomatosis with polyangiitis (GPA). Shotgun metagenomic sequence data were also used to identify protein-encoding genes within the SEED database, and the abundance of proteins then correlated with the presence of bacterial species on an annotated heatmap.ResultsThe presence of S. aureus in the nose as assessed by culture was more frequently detected in patients with active GPA (66.7%) compared with inactive GPA (34.1%). Beta diversity analysis of nasal microbiota by bacterial 16S rRNA profiling revealed a different composition between GPA patients and healthy controls (P = 0.039). Beta diversity analysis of shotgun metagenomic sequence data for Staphylococcus spp. revealed a different composition between active GPA patients and healthy controls and disease controls (P = 0.0007 and P = 0.0023, respectively), and between healthy controls and inactive GPA patients and household controls (P = 0.0168 and P = 0.0168, respectively). Patients with active GPA had a higher abundance of S. aureus, mirroring the culture data, while healthy controls had a higher abundance of S. epidermidis. Staphylococcus pseudintermedius, generally assumed to be a pathogen of cats and dogs, showed an abundance of 13% among the Staphylococcus spp. in our cohort. During long-term follow-up of patients with inactive GPA at baseline, a higher S. aureus abundance was not associated with an increased relapse risk. Functional analyses identified ten SEED protein subsystems that differed between the groups. Most significant associations were related to chorismate synthesis and involved in the vitamin B12 pathway.ConclusionOur data revealed a distinct dysbiosis of the nasal microbiota in GPA patients compared with disease and healthy controls. Metagenomic sequencing demonstrated that this dysbiosis in active GPA patients is manifested by increased abundance of S. aureus and a depletion of S. epidermidis, further demonstrating the antagonist relationships between these species. SEED functional protein subsystem analysis identified an association between the unique bacterial nasal microbiota clusters seen mainly in GPA patients and an elevated abundance of genes associated with chorismate synthesis and vitamin B12 pathways. Further studies are required to further elucidate the relationship between the biosynthesis genes and the associated bacterial species.

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Section: Discussionmentioning

confidence: 99%

The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study

et al. 2019

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“…CUBN is expressed in the kidneys and the intestinal epithelium and is associated with B12-deficient anemia and albuminuria 25 . Cobalamin is required for hostmicrobial interactions 26 , and supplementation with cobalamin for seven days induced a substantial shift in the microbiota composition of an in vitro colon model 27 . These associations suggest that some members of the gut microbiome community might be affected by genetic variants that regulate the absorption and metabolism of vitamins B2 and B12.…”

Section: Heterogeneity Of Microbiome Composition Reduces the Power Ofmentioning

confidence: 99%

Large-scale association analyses identify host factors influencing human gut microbiome composition

Kurilshikov¹,

Medina‐Gomez²,

Bacigalupe³

et al. 2020

Preprint

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AbstractTo study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed whole-genome genotypes and 16S fecal microbiome data from 18,473 individuals (25 cohorts). Microbial composition showed high variability across cohorts: we detected only 9 out of 410 genera in more than 95% of the samples. A genome-wide association study (GWAS) of host genetic variation in relation to microbial taxa identified 30 loci affecting microbome taxa at a genome-wide significant (P<5×10-8) threshold. Just one locus, the lactase (LCT) gene region, reached study-wide significance (GWAS signal P=8.6×10−21); it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.94×10−10<P<5×10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization analyses identified enrichment of microbiome trait loci SNPs in the metabolic, nutrition and environment domains and indicated food preferences and diseases as mediators of genetic effects.

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“…The novel 359pathways showing in-host convergence may be important for interactions between host and 360 pathogen arising from either metabolic or immune pressure. Mtb is one of a few types of bacteria 361 that possess the capacity for de novo coenzyme B12/cobalamin synthesis, and this pathway has 362 been implicated in Mtb survival in-host and Mtb growth(Rowley and Kendall 2019). We 363 identified four genetic variants that developed in three separate patients and in three consecutive 364 genes from the same locus cobG, intergenic cobG-cobH, cobH and cobK (Rv2064-Rv2067).…”

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confidence: 99%

In-host population dynamics ofM. tuberculosisduring treatment failure

Vargas

Freschi

Marin

et al. 2019

Preprint

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To B12 or not to B12: Five questions on the role of cobalamin in host-microbial interactions

Cited by 73 publications

References 23 publications

The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study

The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study

Large-scale association analyses identify host factors influencing human gut microbiome composition

In-host population dynamics ofM. tuberculosisduring treatment failure

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