Topical emollient therapy with sunflower seed oil alters the skin microbiota of young children with severe acute malnutrition in Bangladesh: A randomised, controlled study

Abstract

Background: Topical emollient therapy with sunflower seed oil (SSO) reduces risk of sepsis and mortality in very preterm infants in low- or middle-income countries (LMICs). Proposed mechanisms include modulation of skin and possibly gut barrier function. The skin and gut microbiota play important roles in regulating barrier function, but the effects of emollient therapy on these microbiotas are poorly understood.

Methods: We characterised microbiota structure and diversity with 16S rRNA gene amplicon sequence data and ecological statistics in 20 children with severe acute malnutrition (SAM) aged 2-24 months, at four skin sites and in stool, during a randomised, controlled trial of emollient therapy with SSO in Bangladesh. Microbes associated with therapy were identified with tree-based sparse discriminant analysis.

Results: The skin microbiota of Bangladeshi children with SAM was highly diverse and displayed significant variation in structure as a function of physical distance between sites. Microbiota structure differed between the study groups (P = 0.005), was more diverse in emollient-treated subjects-including on the forehead which did not receive direct treatment-and changed with each day (P = 0.005) at all skin sites. Overall, Prevotellaceae were the most differentially affected by emollient treatment; several genera within this family became more abundant in the emollient group than in the controls across several skin sites. Gut microbiota structure was associated with sample day (P = 0.045) and subject age (P = 0.045), but was not significantly affected by emollient treatment (P = 0.060).

Conclusions: Emollient therapy altered the skin microbiota in a consistent and temporally coherent manner. We speculate that therapy with SSO enhances skin barrier function in part through alterations in the microbiota, and through systemic mechanisms. Strategies to strengthen skin and gut barrier function in populations at risk, such as children in LMICs like Bangladesh, might include deliberate manipulation of their skin microbiota.

Trial registration: ClinicalTrials.gov: NCT02616289.

Conflict of interest statement

Competing interests: The following authors are current or former employees and shareholders of GlaxoSmithKline: Lindsay Kendall, Jonathan Crowther and Rachel Gibson. The authors have completed the ICMJE competing interests form (available upon request from the corresponding author), and declare no further conflicts of interest.

Copyright © 2021 by the Journal of Global Health. All rights reserved.

Figures

Figure 1

Baseline diversity and structure of the skin microbiota in Bangladeshi children with severe acute malnutrition (SAM) at four different body sites. Bacterial DNA was extracted from skin swabs and fecal samples of 20 Bangladeshi children with SAM at time of enrollment. A) Comparison of mean Shannon diversity between skin sites and stool (Wilcoxon test, *P < 0.05, ***P < 0.001). B) Microbiota structure at skin sites by Family, color-coded by phylum: shades of blue = Actinobacteria, shades of green = Bacteroidetes, shades of yellow = Firmicutes, shades of orange = Proteobacteria; light grey = amplicon sequence variants (ASVs) with relative abundance <0.1%, dark grey = ASVs without taxonomic assignment. C) Principal coordinates analysis (PCoA) of the Bray-Curtis dissimilarity for skin samples at baseline. Coordinates were centered per subject. Dark green = volar forearm, light green = elbow crease, orange = shin, purple = forehead.

Figure 2

Similarity of microbiota structure at different skin sites within and between Bangladeshi children with severe acute malnutrition (SAM). A) Comparison of mean Bray-Curtis dissimilarity between baseline samples from different and the same skin sites within and between children. B) Comparison of mean Bray-Curtis dissimilarity between baseline samples from different skin sites of the same child. C) Linear regression of mean Bray-Curtis dissimilarity against physical distance between body sites (assigned ranks: volar forearm-elbow crease = 1, volar forearm-forehead = 2, volar forearm-shin = 2, elbow crease-shin = 2, forehead-shin = 3). Grey shaded area represents the 95% confidence interval (CI). P values are displayed for between-sample comparisons (Wilcoxon test, ***P < 0.001).

Figure 3

Temporal trends in skin microbiota diversity during the study period per skin site and treatment group in Bangladeshi children with severe acute malnutrition (SAM) undergoing topical emollient therapy. Mean Shannon diversity index was calculated per sample day, skin site, and study group, and compared using the Wilcoxon test (*P < 0.05). Blue bars = control group, yellow bars = emollient group.

Figure 4

Skin microbiota structure during the study period per skin site and treatment group in Bangladeshi children with severe acute malnutrition (SAM) undergoing topical emollient therapy. Principal coordinates analysis (PCoA) of the Bray-Curtis dissimilarity was performed per skin site and treatment group. Color gradient: sample days, light green = early days, purple = later days.

Figure 5

Bacterial taxa with significant differences in abundance between treatment groups during the second half of treatment in Bangladeshi children with severe acute malnutrition (SAM) undergoing topical emollient therapy. The mean relative abundance of amplicon sequence variants (ASVs) identified by linear discriminant analysis as differentiating between the treatment groups on days 6-10 was calculated per subject and skin site. Means were compared using the Wilcoxon test. **P < 0.01, *P < 0.05. The P values presented here were not corrected for multiple comparisons. ASVs are presented by skin site. Blue bars = control group, yellow bars = emollient group.

Figure 6

Phylogenetic tree of amplicon sequence variants (ASVs) that discriminated between treatment groups in Bangladeshi children with severe acute malnutrition (SAM) undergoing topical emollient therapy. Blue symbol = control group, yellow symbol = emollient group; square = volar forearm, circle = elbow crease, triangle = forehead, diamond = shin. Background color indicates phylum (yellow = Firmicutes, blue = Actinobacteria, green = Bacteroidetes, orange = Proteobacteria).

Figure 7

Gut microbiota diversity and structure during the study period in Bangladeshi children with severe acute malnutrition (SAM) undergoing topical emollient therapy. A) Mean Shannon diversity was calculated for each day and compared between study groups. B) Principal coordinates analysis (PCoA) was performed on the Bray-Curtis dissimilarity between stool samples. Color gradient: sample days, light green = early days, purple = later days.