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Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis.

ABSTRACT: Various diseases have been linked to the human microbiota, but the underlying molecular mechanisms of the microbiota in disease pathogenesis are often poorly understood. Using acne as a disease model, we aimed to understand the molecular response of the skin microbiota to host metabolite signaling in disease pathogenesis. Metatranscriptomic analysis revealed that the transcriptional profiles of the skin microbiota separated acne patients from healthy individuals. The vitamin B12 biosynthesis pathway in the skin bacterium Propionibacterium acnes was significantly down-regulated in acne patients. We hypothesized that host vitamin B12 modulates the activities of the skin microbiota and contributes to acne pathogenesis. To test this hypothesis, we analyzed the skin microbiota in healthy subjects supplemented with vitamin B12. We found that the supplementation repressed the expression of vitamin B12 biosynthesis genes in P. acnes and altered the transcriptome of the skin microbiota. One of the 10 subjects studied developed acne 1 week after vitamin B12 supplementation. To further understand the molecular mechanism, we revealed that vitamin B12 supplementation in P. acnes cultures promoted the production of porphyrins, which have been shown to induce inflammation in acne. Our findings suggest a new bacterial pathogenesis pathway in acne and provide one molecular explanation for the long-standing clinical observation that vitamin B12 supplementation leads to acne development in a subset of individuals. Our study discovered that vitamin B12, an essential nutrient in humans, modulates the transcriptional activities of skin bacteria, and provided evidence that metabolite-mediated interactions between the host and the skin microbiota play essential roles in disease development.

SUBMITTER: Kang D

PROVIDER: S-EPMC6049814 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis.

Kang Dezhi D Shi Baochen B Erfe Marie C MC Craft Noah N Li Huiying H

Science translational medicine 20150601 293

Various diseases have been linked to the human microbiota, but the underlying molecular mechanisms of the microbiota in disease pathogenesis are often poorly understood. Using acne as a disease model, we aimed to understand the molecular response of the skin microbiota to host metabolite signaling in disease pathogenesis. Metatranscriptomic analysis revealed that the transcriptional profiles of the skin microbiota separated acne patients from healthy individuals. The vitamin B12 biosynthesis pat ...[more]

PMID: 26109103

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Project description:ImportanceGiven the widespread use of systemic antibiotics for treatment of moderate to severe acne, it is important to understand the associations of such antibiotic use with changes not only in Cutibacterium acnes (formerly Propionibacterium acnes) but also in the complete bacterial community of the skin.ObjectiveTo examine the composition, diversity, and resilience of skin microbiota associated with systemic antibiotic perturbation in individuals with acne.Design, setting, and participantsThis longitudinal cohort study conducted at an academic referral center in Maryland from February 11 to September 23, 2014, included 4 female participants who had received a recent diagnosis of acne vulgaris, showed comedonal and inflammatory acne on the face, were at least 18 years old, and had no recent use of systemic or topical treatments for acne, including antibiotics and retinoids. Data analysis was performed between July 5, 2017, and November 7, 2018.InterventionsParticipants were prescribed oral minocycline, 100 mg, twice daily for 4 weeks. Skin areas on the forehead, cheek, and chin were sampled for 16S ribosomal RNA gene sequencing at baseline, 4 weeks after starting minocycline treatment, and then 1 week and 8 weeks after discontinuation of treatment.Main outcomes and measuresSkin microbiota examined with respect to relative abundance of bacterial taxa, α diversity (represents within-sample microbial diversity), and β diversity (represents between-sample microbial diversity). Acne status evaluated with photography and lesion count.ResultsOf the 4 patients included in this study, 2 were 25 years old, 1 was 29 years old, and 1 was 35 years old; 2 were white women, 1 was an African American woman, and 1 was an Asian woman. Across all 4 patients, antibiotic treatment was associated with a 1.4-fold reduction in the level of C acnes (difference, -10.3%; 95% CI, -19.9% to -0.7%; P = .04) with recovery following cessation of treatment. Distinct patterns of change were identified in multiple bacterial genera, including a transient 5.6-fold increase in the relative abundance of Pseudomonas species (difference, 2.2%; 95% CI, 0.9%-3.4%; P < .001) immediately following antibiotic treatment, as well as a persistent 1.7-fold increase in the relative abundance of Streptococcus species (difference, 5.4%; 95% CI, 0.3%-10.6%; P = .04) and a 4.7-fold decrease in the relative abundance of Lactobacillus species (difference, -0.8%; 95% CI, -1.4% to -0.2%; P = .02) 8 weeks following antibiotic treatment withdrawal. In general, antibiotic administration was associated with an initial decrease from baseline of bacterial diversity followed by recovery. Principal coordinates analysis results showed moderate clustering of samples by patient (analysis of similarity, R = 0.424; P = .001) and significant clustering of samples by time in one participant (analysis of similarity, R = 0.733; P = .001).Conclusions and relevanceIn this study, systemic antibiotic treatment of acne was associated with changes in the composition and diversity of skin microbiota, with variable rates of recovery across individual patients and parallel changes in specific bacterial populations. Understanding the association between systemic antibiotic use and skin microbiota may help clinicians decrease the likelihood of skin comorbidities related to microbial dysbiosis.

Project description:Vitamin B12 is synthesized by prokaryotes in the rumens of dairy cows-and this has implications in human nutrition since humans rely on consumption of dairy products for vitamin B12 acquisition. However, the concentration of vitamin B12 in milk is highly variable, and there is interest in determining what causes vitamin B12 variability. We collected 92 temporally linked rumen, fecal, blood, and milk sample sets from Holstein cows at various stages of lactation fitted with rumen cannula and attempted to define which bacterial genera correlated well with vitamin B12 abundance. The level of vitamin B12 present in each sample was measured, and the bacterial population of each rumen, fecal, and milk sample (n?=?263) was analyzed by 16S rRNA-targeted amplicon sequencing of the V4 region. The bacterial populations present in the rumen, small intestine, and milk were highly dissimilar. Combined diet and lactation status had significant effects on the composition of the microbiota in the rumen and in the feces. A high ruminal concentration of vitamin B12 was correlated with the increased abundance of Prevotella, while a low ruminal concentration of vitamin B12 was correlated with increased abundance of Bacteroidetes, Ruminiclostridium, and Butyrivibrio The ultimate concentration of vitamin B12 is controlled by the complex interaction of several factors, including the composition of the microbiota. Bacterial consumption of vitamin B12 in the rumen may be more important in determining overall levels than bacterial production.IMPORTANCE In this paper, we examined the microbiome of the bovine rumen, feces, and milk and attempted to understand how the bacterial communities at each site affected the production and movement of vitamin B12 around the animal's body. It was determined that the composition of the bovine rumen microbiome correlates well with vitamin B12 concentration, indicating that the rumen microbiota may be a good target for manipulation to improve production of this important vitamin.

Project description:Systemic antibiotics are extensively used to control moderate to severe acne. Hence, it is crucial to understand their impact on the skin microbiota, which is supposedly perturbed. The purpose of this study was to compare the makeup and diversity of the skin microbiota in acne patients before and after taking oral antibiotics. A longitudinal cohort study was performed on 20 participants with moderate to severe facial acne with no recent use of oral and topical antibiotics/retinoids. Patients were prescribed oral doxycycline, 100 mg, twice daily for six weeks. Skin areas on the cheek were sampled for 16S ribosomal RNA gene sequencing at baseline, and after six weeks of doxycycline treatment. Ten males and 10 females aged 11 to 44 years with a median Investigator's Global Assessment score of 3 (moderate) were enrolled. At baseline, Cutibacterium acnes (formerly Propionibacterium acnes) was the most dominant species followed by Staphylococcus epidermidis. Acne severity showed a positive correlation with the abundance of Cutibacterium acnes. Across all subjects, antibiotic treatment reduced clinical acne grades and was associated with a 1.96-fold reduction in the relative abundance of Cutibacterium acnes (p = 0.01, 95% CI -22% to -3%). Marked changes were also identified in other bacterial species, such as Cutibacterium granulosum (formerly Propionibacterium granulosum), which increased by 4.46-fold (p = 0.02, 95% CI 0.004% to 0.9%) in the treated samples. In general, antibiotics administration was associated with an increase in bacterial diversity (alpha diversity). Principal coordinates analysis showed mild clustering of samples by patient (analysis of similarity, R = 0.135, p = 0.04) whereas there was scant clustering with treatment (ANOSIM, R = 0.005; p = 0.29). In conclusion, we found individuals with acne to have a unique microbial signature. Acne treatment with systemic antibiotics was associated with changes in the composition and diversity of skin microbiota, especially Cutibacterium acnes, which correlates with acne severity. Our study provides insight into the skin microbiota in acne and how it is modulated by systemic antibiotics.

Project description:Purpose: Inflammatory bowel disease (IBD) refers to a spectrum of autoimmune diseases, which result in chronic intestinal inflammation. Previous findings suggest a role for diet, nutrition and dysbiosis of the gut microbiota in both the development and progression of the condition. Vitamin B12 is a key cofactor of methionine synthase and is produced solely by microbes. Previous work links increased levels of homocysteine, a substrate of methionine synthase, MetH, to IBD indicating a potential role for vitamin B12 deficiency in intestinal injury and inflammation. This study assessed the role of vitamin B12 in shaping the gut microbiota and determining responses to intestinal injury using a reproducible murine model of colitis. Methods: The effects of vitamin B12 supplementation and deficiency were assessed in vivo; 3-week-old post-weanling C57Bl/6 mice were divided into three dietary treatment groups: (1) sufficient vitamin B12 (50 mg/Kg), (2) deficient vitamin B12 (0 mg/Kg) and (3) supplemented vitamin B12 (200 mg/Kg) for a period of 4 weeks. Intestinal injury was induced with 2% dextran sodium sulphate (DSS) via drinking water for 5 days. The impact of varying levels of dietary vitamin B12 on gut microbiota composition was assessed using 16S rRNA gene sequencing from fecal samples collected at day 0 and day 28 of the dietary intervention, and 7 days following induction of colitis on day 38, when blood and colonic tissues were also collected. Results: No significant alterations were found in the gut microbiota composition of disease-free animals in response to dietary interventions. By contrast, after DSS-induced colitis, >30 genera were significantly altered in vitamin B12 deficient mice. Altered B12 levels produced no significant effect on composite disease-activity scores; however, administration of a B12 deficient diet resulted in reduced DSS-induced epithelial tissue damage. Conclusions: Vitamin B12 supplementation does not alter the gut microbiota composition under healthy conditions, but does contribute to differential microbial responses and intestinal dysbiosis following the induction of experimental colitis.

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Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis.

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Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis.

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