A randomized clinical study on the effects of emollient use on the developing infant skin microbiome and metabolome

Abstract

There is little debate that the microbiome plays an overall role in health; however, there is much to be learned about potential factors influencing the microbiome, particularly that of the skin, since it has the most exposure to the environment. It has been shown that the skin microbiome of newborns evolves to an infant-like profile, after rapid diversification throughout the neonatal period and into infancy.1 Evidence shows that the presence of certain commensal microbial species limits access to opportunistic pathogens and may play a role in immune modulation.2 By contrast, an alteration in the relative abundances of bacteria has been shown to be related to certain skin diseases. For example, the diversity of the skin microbiome is decreased in patients with atopic dermatitis (AD).3 Emollients are frequently used in AD management because of their effects on improving the skin barrier and reversing microbial dysbiosis.4 Limited information is available on the effects of skin care products on the microbiome of healthy individuals. One study in adults suggested that the microbiome can be altered by skin care products.5 The current report is the first study to evaluate the impact of baby skin care products on the microbiome in infants. More specifically, we evaluated if the addition of an emollient, which has been shown to enhance the richness and diversity of the microbiome in AD, would have a similar effect in healthy infants when added to the regimen of baby bath wash. The effects of a skincare regimen combining a topical emollient lotion with a mild cleanser were compared with the use of the cleanser alone on the skin surface microbiome and metabolome of healthy infants (3–6 months old) in a randomized, evaluator-blind, 5-week study (ClinicalTrials.gov NCT03457857). Inclusion and exclusion criteria are provided in Table S1. During a 7-day washout period, parents were instructed to use a marketed gentle baby cleanser (JOHNSON'S® HEAD-TO-TOE® Baby Wash & Shampoo; Johnson & Johnson Consumer Inc., Skillman, NJ, USA) at least three times per week in place of their infant's usual body cleanser and refrain from the use of any type of moisturizer or lotion. Infants were randomized to either wash-only or wash + lotion groups for a 28-day treatment period. Both the test cleanser (JOHNSON's® CottonTouch® Newborn Wash & Shampoo) and the lotion (JOHNSON'S® CottonTouch® Newborn Face & Body Lotion) were marketed as mild products designed for newborns. Product key ingredients are provided in Table S2. The lotion combines glycerol, fatty acids, and other emollients in a proprietary formulation. The cleanser was used at least three times per week (maximum once per day). The lotion was applied daily (once or twice), with one application after bathing on a “bath day.” The 28-day period was followed by 3–5 days' regression, during which both groups followed a regimen identical to the initial washout period. Full details of clinical evaluation, assessment of moisturization and pH of the skin, and collection of samples for skin microbiome and metabolome assessment are in the Supplementary Methods. Of 38 participants enrolled in the study, 32 were included in the efficacy analysis and 30 completed the study (Figure S1). Mean (±SD) age was 4.0 (±1.2) months (Table S3). Microbiome richness increased for both groups during the period of the study compared with baseline and was maintained during regression (Figure 1A). Microbiome richness was statistically higher for the wash + lotion group compared with the wash-only group on Day 28, showing that adding lotion to a skincare regimen can positively affect the infant skin microbiome. Increased richness is the first step toward increased diversity, which is associated with healthy skin. The relative abundance profile of the microbiome was similar in both groups (Figure 1B), and microbiome diversity remained statistically unchanged throughout the study (Figure S2). For the wash + lotion group, reduced protein breakdown compared with the wash-only group and increased levels compared with the baseline of important components of the skin barrier function, including ceramides (Figure 1C). An increase in free fatty acids and glycerol was observed (Figures S3 and S4); however, glycerol levels likely reflect deposition on the skin surface following lotion application. No significant changes from baseline in Corneometer values were observed in either group, and no significant differences were observed between groups during the treatment period. A mildly acidic (pH 4.5–6.0) skin surface plays an important role in maintaining a healthy skin barrier and in regulating bacterial activity.6 Skin pH remained mildly acidic throughout the study regardless of treatment. No significant change was observed between groups (Table S4A,B). Both products were well-tolerated, and no significant changes in the clinical assessment of skin were observed for either group. Detailed safety data are in the Supplementary Results. Limitations of this study include the smaller than planned number of subjects enrolled, and the recruitment of subjects was from one geographical area (central New Jersey). Despite the low participant numbers, the study was able to demonstrate statistical differences between the treatment groups and between timepoints. Results suggest that the routine use of an appropriately formulated emollient in infants increases their skin microbiome richness as well as the levels of ceramides and free fatty acids that play an important role in skin barrier integrity. All authors were involved in the study design, analysis of the data, and interpretation of the data. All authors were involved in the drafting of the manuscript and have read and approved the final version. The authors received writing and editorial support from Susan Sutch, PharmD, on behalf of Evidence Scientific Solutions, Ltd., and funded by Johnson & Johnson Consumer Inc. This study was funded by Johnson & Johnson Consumer Inc. DLF and LST are employees of Johnson & Johnson Consumer Inc. KAC was an employee of Johnson & Johnson Consumer Inc. at the time the research was conducted and analysed. JN is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson. GNS is an employee of Johnson & Johnson Santé Beauté France. The data that support the findings of this study are available from the corresponding author upon reasonable request. Raw data are available at the Sequence Read Archive (Bioproject: PRJNA707369). Appendix S1. Supplementary Methods and Results. Figure S1. Participant flow and disposition. Figure S2. (A) Diversity of the microbiome remained unchanged in both groups throughout all phases of the study. (B) Microbial richness significantly increased from baseline on Days 14 and 28 in the wash-only group (*p < 0.05) and on Day 28 in the wash + lotion group (*p < 0.05). Figure S3. Bubble plot of the effects of wash vs. wash + lotion on protein breakdown. Figure S4. Change in levels of (a) caprylate and (b) glycerol from skin surface samples for the two treatment groups. Table S1. Inclusion and exclusion criteria. Table S2. (A, B) Test product ingredients. Table S3. Participant demographics. Table S4. Change from baseline statistics for skin (A) Corneometer measurements; (B) pH measurements. 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