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Allergy Levels Allergy levels. FOXP3 trended similarly and was not statistically significant. There were no significant differences in whether the children had received the Lactobacillus pro- biotic in infancy. RISK FACTORS, PREVENTION, AND THE HYGIENE HYPOTHESIS CONCLUSIONS: There are both temporal and long-term variations in specific gut bacterial genera in children Temporal and Long-term Gut Microbiota developing allergic disease. Dietary interventions aimed Variation in Allergic Disease: A Prospective at expanding gut immunomodulatory taxa could be Study from Infancy to School Age studied for preventing allergic disease. Simonyté Sjödin K, Hammarström ML, Rydén P, et al. REVIEWER COMMENTS: The authors describe how certain gut Allergy. 2019;74(1):176–185 organisms, especially commensal Clostridia, colonize PURPOSE OF THE STUDY: How the early-life gut microbiota specific regions of the intestinal mucosa and may play key changes over time has been implicated in the develop- roles as immunomodulators. Given the compelling he- ment of immunoglobulin E– (IgE) mediated allergic reditary nature of atopic disease irrespective of diet, why diseases, but there is lack of data from longitudinal are certain bacterial taxa more or less represented at this studies. In this study, researchers compared gut micro- seemingly important intestinal mucosal location? Might biota from infancy to school age in relation to the onset not gut bacterial taxa be the result of the atopic milieu, of allergic disease while also examining the relationship therefore making efforts to ameliorate atopic disease by of gut microbiota to T-cell activation at age 8 years. the planned ingestion of certain bacteria moot? STUDY POPULATION: Ninety-three children were included from URL: www.pediatrics.org/cgi/doi/10.1542/peds.2019–2461D a randomized, placebo-controlled trial in which researchers investigated the effects of probiotics for primary preven- James R. Banks, MD Timothy Andrews, MD tion of allergic disease. That original trial group consisted of Arnold, Maryland 179 infants without previous allergic manifestations who were randomly assigned to a daily intake of infant cereals with or without the probiotic Lactobacillus paracasei. Effects of Lactobacillus rhamnosus HN001 in Early METHODS: Parents reported signs and symptoms of atopic Life on the Cumulative Prevalence of Allergic disease and medications by using diary cards. Stool samples Disease to 11 Years were collected at 4, 6, and 13 months and at age 8 years. Wickens K, Barthow C, Mitchell EA, et al. Pediatr Allergy Clinical follow-up was conducted at age 8 to 9 years. Clinical Immunol. 2018;29(8):808–814 diagnoses for eczema and asthma were established primarily PURPOSE OF THE STUDY: To determine the efficacy of Lacto- by history, those with allergic rhinitis also had evidence of bacillus rhamnosus supplementation from 35 weeks’ IgE sensitization, and food allergy was diagnosed by history gestation to 2 years of age in reducing the risk of eczema of reaction within 1 hour of food ingestion and/or docu- and other common allergic conditions at 11 years of age. mented IgE sensitization. The gut microbiota was profiled taxonomically using 16S ribosomal RNA gene sequencing. STUDY POPULATION: The study population included pregnant Mononuclear cells from peripheral blood drawn at age 8 women who have a history of asthma, hay fever, or eczema years were polyclonally activated, and levels of interleukin- treated by a doctor or whose partners have a history of 10 and FOXP3 messenger RNA were determined. asthma, hay fever, or eczema treated by a doctor. RESULTS: At age 8 years, 21 children had allergic disease, METHODS: The researchers used a randomized, placebo- with 20 being sensitized to airborne allergens and 13 to controlled parallel trial. Pregnant women were randomly foods. Seventy-two children were nonallergic and non- assigned to 1 of 3 groups: Lactobacillus rhamnosus HN001 sensitized. The longitudinal design allowed for the study (109 colony forming units), Bifidobacteria animalis subsp of compositional changes in gut microbiota from infancy lactis HN019 (109 colony forming units), or placebo. The through school age in relation to development of IgE- treatment was taken orally every day by women until 6 associated allergic disease. Allergic children had temporal months or when they stopped breastfeeding, whichever underrepresentation of Ruminococcus and consistent came first. Infants received daily oral supplementation underrepresentation of Bacteroides, Prevotella, and Cop- from birth to age 2 years. The outcomes reported in this rococcus from infancy through age 8 years. The gut study are (1) current and cumulative prevalence of (since microbiota in 8-year-olds who were allergic was enriched age 6) eczema, defined according to the UK Working in Bifidobacterium and depleted in Lactobacillus, Entero- Party’s Diagnostic Criteria for Atopic Dermatitis; (2) current coccus, and Lachnospira; and in this same group, Faecali- and cumulative prevalence of parental report of asthma, bacterium correlated with interleukin-10 messenger RNA wheeze, and rhinitis, using modified questions from the PEDIATRICS Volume 144, Supplement 1, December 2019 S5 Downloaded from www.aappublications.org/news by guest on September 25, 2021 International Study of Asthma and Allergies in Childhood summary of the original trial results during their child’s questionnaire; and (3) current atopy (assessed by skin prick preschool years, increasing the likelihood of recall bias. It testing to cat pelt, Dermatophagoides pteronyssinus,mixed was also unclear how much of the eczema outcome was grasses, egg white, peanut, and cow’s milk). Results at 2, 4, determined by parent report and how much was de- and 6 years of age for these and other outcomes have been termined by direct observation, so the potential effect of previously reported; results for age 11 years are reported in recall bias on this outcome is unknown. Other limitations this article. The mothers were unblinded at the end of the include the lack of information about eczema severity and the 2-year follow-up, and a summary of the study results was substantial loss to follow-up. Lastly, it would be interesting to provided to families when their children were between 3 understand the effects of probiotic supplementation on food and 4 years of age. An intention-to-treat analysis was sensitization and food allergy, given the hypothesis that food performed to estimate the effect of HN001 and HN019 on allergy may be initiated by cutaneous rather than oral ex- the point prevalences (eg, current eczema) and cumulative posure to the food during infancy. Although in this work, prevalences of the outcomes since age 6 years. along with other similar studies, the researchers provide ev- idence that maternal plus infant supplementation with cer- RESULTS: Overall, 63% of the original study population was tain probiotics reduces the risk of eczema, it is important to assessed at 11 years of age for eczema, and the character- note that many probiotics are sold as dietary supplements, istics of those who dropped out were similar among whichdonotrequireUSFoodandDrugAdministration treatment groups. HN001 supplementation in early life was approval. Therefore, the purity and strength of probiotic associated with a decreased risk of current eczema and products are not guaranteed, and issues in this regard have current hay fever compared with placebo (eczema: 12% vs been well documented. Although probiotics are considered 27%, relative risk [RR]: 0.46 [95% confidence interval (CI): generally safe for healthy individuals, there have been reports 0.25–0.86], P 5 .02; hay fever: 37% vs 50%, RR: 0.73 of severe side effects among those with serious underlying [95% CI: 0.53–1.00], P 5 .05). HN001 was not associated medical conditions or who are immunocompromised. withreducedriskofcurrentatopic sensitization, wheeze, asthma, or rhinitis compared with placebo. HN019 sup- URL: www.pediatrics.org/cgi/doi/10.1542/peds.2019–2461E plementation was only associated with a reduced risk of Elizabeth C. Matsui, MD, MHS current asthma when compared with placebo (17% vs Austin, Texas 29%, RR: 0.59 [95% CI: 0.36–0.96], P 5 .03). For cu- mulative prevalence outcomes, HN001 was associated with a reduced risk of atopic sensitization, eczema, and wheeze, The Protective Effect of Cheese Consumption but not rhinitis, whereas HN019 was not associated with a at 18 Months on Allergic Diseases in the First reduced risk of any of these cumulative atopic outcomes. 6 Years CONCLUSIONS: In this population at high risk for atopic Nicklaus S, Divaret-Chauveau A, Chardon ML, et al; disease, early-life probiotic supplementation with Lacto- Pasture Study Group. Allergy. 2019;74(4):788–798 bacillus rhamnosus HN001, but not Bifidobacteria animalis PURPOSE OF THE STUDY: To evaluate whether cheese con- subsp lactis HN019, was associated with a decreased risk sumption is associated with allergic disease. The hypothesis of current eczema at age 11 and a lower cumulative was based on the notion that cheese is a food potentially prevalence of atopic sensitization, eczema, and wheeze rich in microbial diversity, and immune tolerance to al- from age 6 to 11 when compared with placebo. lergens is associated with the quantity and diversity of the REVIEWER COMMENTS: With this study, the researchers extend microbes that constitute the gut microbiota. the original trial’s findings that HN001 was associated with STUDY POPULATION: The study included 1133 children from decreased risk of incident eczema at ages 2, 4, and 6 to 11 a prospective birth cohort, Protection Against Allergy: years. There is now a growing body of literature pointing Study in Rural Environment, that included children from to the potential of maternal plus infant supplementation rural areas from 5 European countries (Austria, Finland, with certain probiotics to reduce the risk of eczema among France, Germany, and Switzerland). Pregnant women those at high risk for atopic disease, and in this study, it is were recruited during their third trimester of pregnancy. suggested that the protective effects are sustained into later Participants were divided into 2 groups: the farm group, childhood.
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