Altered Gut Microbiota Composition Associated with Eczema in Infants

Huajun Zheng, Hong Liang, Yuezhu Wang, Maohua Miao, Tao Shi, Fen Yang, Enuo Liu, Wei Yuan, Zai-Si Ji, De-Kun Li, Huajun Zheng, Hong Liang, Yuezhu Wang, Maohua Miao, Tao Shi, Fen Yang, Enuo Liu, Wei Yuan, Zai-Si Ji, De-Kun Li

Abstract

Eczema is frequently the first manifestation of an atopic diathesis and alteration in the diversity of gut microbiota has been reported in infants with eczema. To identify specific bacterial communities associated with eczema, we conducted a case-control study of 50 infants with eczema (cases) and 51 healthy infants (controls). We performed high-throughput sequencing for V3-V4 hypervariable regions of the 16S rRNA genes from the gut fecal material. A total of 12,386 OTUs (operational taxonomic units) at a 97% similarity level were obtained from the two groups, and we observed a difference in taxa abundance, but not the taxonomic composition, of gut microbiota between the two groups. We identified four genera enriched in healthy infants: Bifidobacterium, Megasphaera, Haemophilus and Streptococcus; and five genera enriched in infants with eczema: Escherichia/Shigella, Veillonella, Faecalibacterium, Lachnospiraceae incertae sedis and Clostridium XlVa. Several species, such as Faecalibacterium prausnitzii and Ruminococcus gnavus, that are known to be associated with atopy or inflammation, were found to be significantly enriched in infants with eczema. Higher abundance of Akkermansia muciniphila in eczematous infants might reduce the integrity of intestinal barrier function and therefore increase the risk of developing eczema. On the other hand, Bacteroides fragilis and Streptococcus salivarius, which are known for their anti-inflammatory properties, were less abundant in infants with eczema. The observed differences in genera and species between cases and controls in this study may provide insight into the link between the microbiome and eczema risk.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Relative read abundance of different…
Fig 1. Relative read abundance of different bacterial above a cutoff value of 3%.
A: phylum levels; B: genus level. The outer circle represents gut microbiota of healthy infants, and the inner circle represents gut microbiota of eczematous infants.
Fig 2. Networks of all the 170…
Fig 2. Networks of all the 170 bacteria genera revealed in two groups.
Green circle: the unique genera of healthy infants’gut; red circle: the unique genera of eczematous infants. In pie charts, green represents the proportion of this genus in healthy infants and red represents the proportion in eczematous infants. On the top, the nine genera was the most abundance genera (>1% of total DNA sequences in both two groups); the left four genera was enriched in healthy infants, the right five genera was enriched in eczematous infants (q-value

Fig 3. Cladogram of biomarkers for eczematous…

Fig 3. Cladogram of biomarkers for eczematous group.

The red circle represented biomarkers and yellow…

Fig 3. Cladogram of biomarkers for eczematous group.
The red circle represented biomarkers and yellow circles represented non-discriminating taxa. Concentric rings from outside to inside were genus, family, order, class and phylum.
Fig 3. Cladogram of biomarkers for eczematous…
Fig 3. Cladogram of biomarkers for eczematous group.
The red circle represented biomarkers and yellow circles represented non-discriminating taxa. Concentric rings from outside to inside were genus, family, order, class and phylum.

References

    1. Biagini Myers JM, Khurana Hershey GK. Eczema in early life: genetics, the skin barrier, and lessons learned from birth cohort studies. The Journal of pediatrics. 2010;157(5):704–14. 10.1016/j.jpeds.2010.07.009
    1. Bieber T. Atopic dermatitis. The New England journal of medicine. 2008;358(14):1483–94. 10.1056/NEJMra074081 .
    1. Eichenfield LF, Hanifin JM, Beck LA, Lemanske RF Jr., Sampson HA, Weiss ST, et al. Atopic dermatitis and asthma: parallels in the evolution of treatment. Pediatrics. 2003;111(3):608–16. .
    1. von Kobyletzki LB, Bornehag CG, Hasselgren M, Larsson M, Lindstrom CB, Svensson A. Eczema in early childhood is strongly associated with the development of asthma and rhinitis in a prospective cohort. BMC dermatology. 2012;12:11 10.1186/1471-5945-12-11
    1. Saunes M, Oien T, Dotterud CK, Romundstad PR, Storro O, Holmen TL, et al. Early eczema and the risk of childhood asthma: a prospective, population-based study. BMC pediatrics. 2012;12:168 10.1186/1471-2431-12-168
    1. Fiocchi A, Burks W, Bahna SL, Bielory L, Boyle RJ, Cocco R, et al. Clinical Use of Probiotics in Pediatric Allergy (CUPPA): A World Allergy Organization Position Paper. The World Allergy Organization journal. 2012;5(11):148–67. 10.1097/WOX.0b013e3182784ee0
    1. Lilly DM, Stillwell RH. Probiotics: Growth-Promoting Factors Produced by Microorganisms. Science. 1965;147(3659):747–8. .
    1. Toh ZQ, Anzela A, Tang ML, Licciardi PV. Probiotic therapy as a novel approach for allergic disease. Frontiers in pharmacology. 2012;3:171 10.3389/fphar.2012.00171
    1. Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. Nature. 2011;474(7351):327–36. 10.1038/nature10213
    1. Sjogren YM, Jenmalm MC, Bottcher MF, Bjorksten B, Sverremark-Ekstrom E. Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clinical and experimental allergy: journal of the British Society for Allergy and Clinical Immunology. 2009;39(4):518–26. 10.1111/j.1365-2222.2008.03156.x .
    1. Wang M, Karlsson C, Olsson C, Adlerberth I, Wold AE, Strachan DP, et al. Reduced diversity in the early fecal microbiota of infants with atopic eczema. The Journal of allergy and clinical immunology. 2008;121(1):129–34. 10.1016/j.jaci.2007.09.011 .
    1. Forno E, Onderdonk AB, McCracken J, Litonjua AA, Laskey D, Delaney ML, et al. Diversity of the gut microbiota and eczema in early life. Clinical and molecular allergy: CMA. 2008;6:11 10.1186/1476-7961-6-11
    1. Hong PY, Lee BW, Aw M, Shek LP, Yap GC, Chua KY, et al. Comparative analysis of fecal microbiota in infants with and without eczema. PloS one. 2010;5(4):e9964 10.1371/journal.pone.0009964
    1. Yap GC, Loo EX, Aw M, Lu Q, Shek LP, Lee BW. Molecular analysis of infant fecal microbiota in an Asian at-risk cohort-correlates with infant and childhood eczema. BMC research notes. 2014;7:166 10.1186/1756-0500-7-166
    1. Nossa CW, Oberdorf WE, Yang L, Aas JA, Paster BJ, Desantis TZ, et al. Design of 16S rRNA gene primers for 454 pyrosequencing of the human foregut microbiome. World journal of gastroenterology. 2010;16(33):4135–44. PubMed Central PMCID: PMC2932916. 10.3748/wjg.v16.i33.4135 ;
    1. Schloss PD, Gevers D, Westcott SL. Reducing the effects of PCR amplification and sequencing artifacts on 16S rRNA-based studies. PloS one. 2011;6(12):e27310 10.1371/journal.pone.0027310
    1. Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic acids research. 2013;41(Database issue):D590–6. 10.1093/nar/gks1219
    1. Wang Q, Garrity GM, Tiedje JM, Cole JR. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Applied and environmental microbiology. 2007;73(16):5261–7. 10.1128/AEM.00062-07
    1. Cole JR, Wang Q, Cardenas E, Fish J, Chai B, Farris RJ, et al. The Ribosomal Database Project: improved alignments and new tools for rRNA analysis. Nucleic acids research. 2009;37(Database issue):D141–5. 10.1093/nar/gkn879
    1. White JR, Nagarajan N, Pop M. Statistical methods for detecting differentially abundant features in clinical metagenomic samples. PLoS computational biology. 2009;5(4):e1000352 10.1371/journal.pcbi.1000352
    1. Sturn A, Quackenbush J, Trajanoski Z. Genesis: cluster analysis of microarray data. Bioinformatics. 2002;18(1):207–8. .
    1. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome biology. 2011;12(6):R60 10.1186/gb-2011-12-6-r60
    1. Baillon S, Hamel JF, Mercier A. Diversity, distribution and nature of faunal associations with deep-sea pennatulacean corals in the Northwest Atlantic. PloS one. 2014;9(11):e111519 10.1371/journal.pone.0111519
    1. Ling Z, Li Z, Liu X, Cheng Y, Luo Y, Tong X, et al. Altered fecal microbiota composition associated with food allergy in infants. Applied and environmental microbiology. 2014;80(8):2546–54. 10.1128/AEM.00003-14
    1. Chiu CM, Huang WC, Weng SL, Tseng HC, Liang C, Wang WC, et al. Systematic analysis of the association between gut flora and obesity through high-throughput sequencing and bioinformatics approaches. BioMed research international. 2014;2014:906168 10.1155/2014/906168
    1. Nylund L, Satokari R, Nikkila J, Rajilic-Stojanovic M, Kalliomaki M, Isolauri E, et al. Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease. BMC microbiology. 2013;13:12 10.1186/1471-2180-13-12
    1. Candela M, Rampelli S, Turroni S, Severgnini M, Consolandi C, De Bellis G, et al. Unbalance of intestinal microbiota in atopic children. BMC microbiology. 2012;12:95 10.1186/1471-2180-12-95
    1. Kim JY, Kwon JH, Ahn SH, Lee SI, Han YS, Choi YO, et al. Effect of probiotic mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the primary prevention of eczema: a double-blind, randomized, placebo-controlled trial. Pediatric allergy and immunology: official publication of the European Society of Pediatric Allergy and Immunology. 2010;21(2 Pt 2):e386–93. 10.1111/j.1399-3038.2009.00958.x .
    1. Rautava S, Kainonen E, Salminen S, Isolauri E. Maternal probiotic supplementation during pregnancy and breast-feeding reduces the risk of eczema in the infant. The Journal of allergy and clinical immunology. 2012;130(6):1355–60. 10.1016/j.jaci.2012.09.003 .
    1. Vael C, Verhulst SL, Nelen V, Goossens H, Desager KN. Intestinal microflora and body mass index during the first three years of life: an observational study. Gut pathogens. 2011;3(1):8 10.1186/1757-4749-3-8
    1. Gronlund MM, Arvilommi H, Kero P, Lehtonen OP, Isolauri E. Importance of intestinal colonisation in the maturation of humoral immunity in early infancy: a prospective follow up study of healthy infants aged 0–6 months. Archives of disease in childhood Fetal and neonatal edition. 2000;83(3):F186–92. 10.1136/fn.83.3.F186
    1. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122(1):107–18. 10.1016/j.cell.2005.05.007 .
    1. Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature. 2008;453(7195):620–5. 10.1038/nature07008 .
    1. Troy EB, Kasper DL. Beneficial effects of Bacteroides fragilis polysaccharides on the immune system. Frontiers in bioscience. 2010;15:25–34.
    1. Ochoa-Reparaz J, Mielcarz DW, Ditrio LE, Burroughs AR, Begum-Haque S, Dasgupta S, et al. Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. Journal of immunology. 2010;185(7):4101–8. 10.4049/jimmunol.1001443 .
    1. Sonoyama K, Ogasawara T, Goto H, Yoshida T, Takemura N, Fujiwara R, et al. Comparison of gut microbiota and allergic reactions in BALB/c mice fed different cultivars of rice. The British journal of nutrition. 2010;103(2):218–26. 10.1017/S0007114509991589 .
    1. Di Giacinto C, Marinaro M, Sanchez M, Strober W, Boirivant M. Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. Journal of immunology. 2005;174(6):3237–46. .
    1. Joossens M, Huys G, Cnockaert M, De Preter V, Verbeke K, Rutgeerts P, et al. Dysbiosis of the faecal microbiota in patients with Crohn's disease and their unaffected relatives. Gut. 2011;60(5):631–7. 10.1136/gut.2010.223263 .
    1. Beaud D, Tailliez P, Anba-Mondoloni J. Genetic characterization of the beta-glucuronidase enzyme from a human intestinal bacterium, Ruminococcus gnavus. Microbiology. 2005;151(Pt 7):2323–30. 10.1099/mic.0.27712-0 .
    1. Rousseau C, Levenez F, Fouqueray C, Dore J, Collignon A, Lepage P. Clostridium difficile colonization in early infancy is accompanied by changes in intestinal microbiota composition. Journal of clinical microbiology. 2011;49(3):858–65. 10.1128/JCM.01507-10
    1. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006;118(2):511–21. 10.1542/peds.2005-2824 .
    1. Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS biology. 2007;5(7):e177 10.1371/journal.pbio.0050177
    1. Turroni F, Foroni E, Pizzetti P, Giubellini V, Ribbera A, Merusi P, et al. Exploring the diversity of the bifidobacterial population in the human intestinal tract. Applied and environmental microbiology. 2009;75(6):1534–45. 10.1128/AEM.02216-08

Source: PubMed

3
S'abonner