Allergy Asthma Immunol Res.  2020 Mar;12(2):322-337. 10.4168/aair.2020.12.2.322.

Imbalance of Gut Streptococcus, Clostridium, and Akkermansia Determines the Natural Course of Atopic Dermatitis in Infant

  • 1Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
  • 2Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 3Environmental Health Center, Asan Medical Center, Seoul, Korea.
  • 4Department of Life Science, Multidisciplinary Genome Institute, Hallym University, Chuncheon, Korea.
  • 5Department of Pediatrics, Pusan National University Yangsan Hospital, Yangsan, Korea.
  • 6Department of Pediatrics, Mediplex Sejong Hospital, Incheon, Korea.
  • 7Department of Pediatrics, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea.
  • 8Department of Pediatrics, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea.
  • 9Department of Pediatrics, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.
  • 10Department of Pediatrics, Dankuk University Hospital, Cheonan, Korea.
  • 11Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, Korea.
  • 12Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea.
  • 13Department of Pediatrics, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea.
  • 14Department of Pediatrics, Yonsei University of Medicine, Seoul, Korea.
  • 15Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.


The roles of gut microbiota on the natural course of atopic dermatitis (AD) are not yet fully understood. We investigated whether the composition and function of gut microbiota and short-chain fatty acids (SCFAs) at 6 months of age could affect the natural course of AD up to 24 months in early childhood.
Fecal samples from 132 infants were analyzed using pyrosequencing, including 84 healthy controls, 22 transient AD and 26 persistent AD subjects from the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) birth cohort. The functional profile of the gut microbiome was analyzed by whole-metagenome sequencing. SCFAs were measured using gas chromatography-mass spectrometry.
Low levels of Streptococcus and high amounts of Akkermansia were evident in transient AD cases, and low Clostridium, Akkermansia and high Streptococcus were found in children with persistent AD. The relative abundance of Streptococcus positively correlated with scoring of AD (SCORAD) score, whereas that of Clostridium negatively correlated with SCORAD score. The persistent AD group showed decreased gut microbial functional genes related to oxidative phosphorylation compared with healthy controls. Butyrate and valerate levels were lower in transient AD infants compared with healthy and persistent AD infants.
Compositions, functions and metabolites of the early gut microbiome are related to natural courses of AD in infants.


Dermatitis, atopic; gastrointestinal microbiome; metagenome; infant; metabolomics

MeSH Terms

Cohort Studies
Dermatitis, Atopic*
Fatty Acids, Volatile
Gas Chromatography-Mass Spectrometry
Gastrointestinal Microbiome
Oxidative Phosphorylation
Fatty Acids, Volatile


  • Fig. 1 Bacterial alpha and beta-diversity within the gut microbiota of the infant subjects. (A, B) Dotplots of richness (OTUs) and Shannon index of alpha diversity in the gut microbiota were compared among the study groups. (C) The beta-diversity of microbiota was compared using the PCoA plot based on unweighted UniFrac distances. OTU, operational taxonomic unit; PCoA, principal coordinates analysis; ANOVA, analysis of variance; AD, atopic dermatitis.

  • Fig. 2 Phylum and genus compositions of the gut microbiota of the infant subjects. Comparison of bacterial (A) phylum and (B) genus in each group expressed as the mean diameter ± standard error with the P value. Orange denotes the healthy control group, red denotes the transient AD group, and gray denotes the persistent AD group. (C) Comparison of the Streptococcus, Clostridium and Akkermansia compositions within the gut microbiota. The significance of any differences between groups was tested using the Mann-Whitney U test. AD, atopic dermatitis. *P < 0.05; †P < 0.01.

  • Fig. 3 Correlation between the IgE, SCORAD, eosinophil, Streptococcus and Clostridium levels in the infant guts. (A) Relationship between the log transformed relative abundance of Streptococcus in the infant guts and the SCORAD in both the transient and persistent AD groups. (B) Relationship between the log transformed relative abundance of Streptococcus in the infant guts and log transformed total IgE (IU/mL) in both the transient and persistent AD groups. (C) Relationship between the log transformed relative abundance of Streptococcus in the infant guts and log transformed eosinophil level (%) in both the transient and persistent AD groups. (D) Relationship between the log transformed relative abundance of Clostridium in the infant guts and log transformed SCORAD in both the transient and persistent AD groups. (E) Relationship between the log transformed relative abundance of Clostridium in the infant guts and log transformed total IgE (IU/mL) in both the transient and persistent AD groups. (F) Relationship between the log transformed relative abundance of Clostridium in the infant guts and log transformed eosinophil level (%) in both the transient and persistent AD groups. IgE, immunoglobulin E; SCORAD, scoring of atopic dermatitis; AD, atopic dermatitis.

  • Fig. 4 Comparison of the metabolic pathways in the infant gut microbiota using metagenome analysis. Comparison of the functional genes related to oxidative phosphorylation and their contributing species among the study groups. Black arrow denotes Akkermansia muciniphila, P = 0.094. AD, atopic dermatitis. *P = 0.001.

  • Fig. 5 Comparison of SCFAs between 3 groups. Comparison of (A) acetate, (B) propionate, (C) butyrate, (D) valerate between among the groups *P < 0.01; †P < 0.05; ‡P < 0.01. AD, atopic dermatitis; SCFA, short chain fatty acid.

  • Fig. 6 Potential model for compositions, functions and metabolites of the gut microbiome according to the natural course of AD. AD, atopic dermatitis; SCFA, short chain fatty acid.


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