Probiotic Intervention on the Development of Allergic Diseases in Infants Exposed to Antibiotics Early in Life

Официальное название

A Study on the Impact of Probiotic Intervention on the Development of Allergic Diseases in Infants Exposed to Antibiotics Early in Life

Обзор

Early antibiotic exposure is an important environmental factor that disrupts the establishment of the infant gut microbiota and leads to microbial dysbiosis. Accumulating epidemiological evidence indicates that exposure to antibiotics early in life (including both prenatal and postnatal periods) is significantly associated with an increased risk of allergic diseases in childhood. As live microorganisms, probiotics hold potential as a preventive strategy against allergies due to their ability to stabilize the intestinal barrier and regulate immune balance (e.g., promoting Th1/Th2 balance, inducing regulatory T cells, and increasing sIgA secretion). However, current studies have mostly focused on general or high-risk infant populations. For the specific high-risk subgroup that has already been exposed to antibiotics early in life, high-quality randomized controlled trial evidence is still lacking regarding whether probiotic intervention can effectively reduce the incidence of allergies and whether it exerts its effects by reshaping the gut microbiota and metabolites disrupted by antibiotics. This study focuses on breastfed infants who received antibiotics during the early postnatal period (within 30 days after birth) and aims to investigate the effect of a probiotic mixture containing Bifidobacterium longum subsp. infantis R0033, Lactobacillus helveticus R0052, and Bifidobacterium bifidum R0071 on the development of allergic diseases after antibiotic exposure.

Подробное описание

Allergic diseases are a major global public health problem, affecting approximately 30%-40% of the population. Food allergy (FA) often represents the starting point of the atopic march in children and can subsequently progress to atopic dermatitis, asthma, allergic rhinitis, and other conditions, severely impacting quality of life. Early life is a critical "window period" for the development and maturation of the immune system, in which the gut microbiota plays a central role. The interaction between the gut microbiota and the host immune system is essential for the establishment of immune tolerance.

Early antibiotic exposure is an important environmental factor that disrupts the establishment of the infant gut microbiota and leads to microbial dysbiosis. Accumulating epidemiological evidence indicates that exposure to antibiotics early in life (including both prenatal and postnatal periods) is significantly associated with an increased risk of allergic diseases in childhood. The underlying mechanism may involve antibiotic-induced disruption of the gut microbiota, which in turn affects immune balance and skews the immune response toward a Th2-dominant (allergy-prone) phenotype. However, the specific host-microbiota interactions involved have not yet been fully elucidated.

As live microorganisms, probiotics hold potential as a preventive strategy against allergies due to their ability to stabilize the intestinal barrier and regulate immune balance (e.g., promoting Th1/Th2 balance, inducing regulatory T cells, and increasing secretory IgA secretion). However, current studies have mostly focused on general or high-risk infant populations. For the specific high-risk subgroup that has already been exposed to antibiotics early in life, high-quality randomized controlled trial evidence is still lacking regarding whether probiotic intervention can effectively reduce the incidence of allergies and whether it exerts its effects by reshaping the gut microbiota and metabolites disrupted by antibiotics.

This study focuses on breastfed infants who received antibiotics during the early postnatal period (within 30 days after birth) and aims to investigate the effect of a probiotic mixture on the development of allergic diseases after antibiotic exposure.

The study plans to enroll infants with early-life antibiotic exposure as the study population. Starting at 1 month of age, they will be randomly assigned to a probiotic intervention group or a placebo group, while infants who have never received antibiotics will be included as a control group.

Infants in the intervention group will receive an oral probiotic formulation for 8 weeks, whereas those in the placebo group will receive a placebo without probiotics. During the one-year follow-up period, the occurrence of food allergic diseases in each group will be documented in detail, including the time of onset, type, and severity of symptoms. In addition, growth and development indicators, gut microbiota composition, and metabolomic profiles will be regularly monitored to further explore the potential mechanisms of action of the probiotic intervention.

Вмешательства

• Пищевая добавка Probiotic mixture
  Oral probiotic mixture for 8 weeks, once daily, one sachet per day
• Другое Placebo
  Oral a placebo without probiotics for 8 weeks, once daily, one sachet per day.

Первичные конечные точки

• Incidence of allergic diseases in infants [Срок оценки: Follow up until the enrolled infants reach 1 year of age.]
• Changes in gut microbiota composition in the antibiotic-exposed group [Срок оценки: At enrollment (1 month of age) and at 3, 6, and 12 months of age]
• Changes in fecal metabolites in infants of the probiotic intervention group [Срок оценки: At 3, 6, and 12 months of age]

Вторичные конечные точки (2)

• Growth curves of infants in the antibiotic-exposed group and the control group [Срок оценки: At 3, 6, 9, and 12 months of age.]
• Proportion of infectious diseases in infants of the antibiotic-exposed group and the control group [Срок оценки: Follow up until the infant reaches 1 year of age.]

Критерии участия

Критерии включения

• Gestational age from 37 weeks to less than 41 weeks;
• Birth weight between the 10th and 90th percentiles for gestational age;
• Breastfed (exclusively breastfed after achieving stable feeding volume, with willingness to maintain exclusive breastfeeding for at least 3 months);
• Postnatal age within 35 days; Consent to participate in this study.

Критерии исключения

• Postnatal Apgar score <7;
• Presence of severe congenital malformations or inherited metabolic diseases;
• Use of probiotics by the infant or the mother within 2 weeks before enrollment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Peking University Third Hospital — Пекин

Публикации

• Baron R, Taye M, der Vaart IB, Ujcic-Voortman J, Szajewska H, Seidell JC, Verhoeff A. The relationship of prenatal antibiotic exposure and infant antibiotic administration with childhood allergies: a systematic review. BMC Pediatr. 2020 Jun 27;20(1):312. doi: 10.1186/s12887-020-02042-8. PMID 32593308
• Brough HA, Lanser BJ, Sindher SB, Teng JMC, Leung DYM, Venter C, Chan SM, Santos AF, Bahnson HT, Guttman-Yassky E, Gupta RS, Lack G, Ciaccio CE, Sampath V, Nadeau KC, Nagler CR. Early intervention and prevention of allergic diseases. Allergy. 2022 Feb;77(2):416-441. doi: 10.1111/all.15006. Epub 2021 Sep 7. PMID 34255344
• Ding M, Li B, Chen H, Ross RP, Stanton C, Jiang S, Zhao J, Chen W, Yang B. Bifidobacterium longum subsp. infantis regulates Th1/Th2 balance through the JAK-STAT pathway in growing mice. Microbiome Res Rep. 2024 Jan 19;3(2):16. doi: 10.20517/mrr.2023.64. eCollection 2024. PMID 38841405
• Shamji MH, Fulton WT, Animashaun I, Palmer E, Baerenfaller K, Sokolowska M, Barber D, Huffaker M, Baloh C, Pfaar O, Ollert M, Klimek L, Rabin RL, Tripathi A, Togias A, Vieths S, Shreffler WG, Layhadi JA. Multiomics approach to evaluating personalized biomarkers of allergen immunotherapy. J Allergy Clin Immunol. 2025 Sep;156(3):523-534. doi: 10.1016/j.jaci.2025.06.036. PMID 40914606
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• Grimshaw KEC, Roberts G, Selby A, Reich A, Butiene I, Clausen M, Dubakiene R, Fiandor A, Fiocchi A, Grabenhenrich LB, Larco JI, Kowalski ML, Rudzeviciene O, Papadopoulos NG, Rosenfeld L, Sigurdardottir ST, Sprikkelman AB, Schoemaker AA, Xepapadaki P, Mills ENC, Keil T, Beyer K. Risk Factors for Hen's Egg Allergy in Europe: EuroPrevall Birth Cohort. J Allergy Clin Immunol Pract. 2020 Apr;8(4):1341- PMID 31846795
• Metzler S, Frei R, Schmausser-Hechfellner E, von Mutius E, Pekkanen J, Karvonen AM, Kirjavainen PV, Dalphin JC, Divaret-Chauveau A, Riedler J, Lauener R, Roduit C; PASTURE/EFRAIM study group. Association between antibiotic treatment during pregnancy and infancy and the development of allergic diseases. Pediatr Allergy Immunol. 2019 Jun;30(4):423-433. doi: 10.1111/pai.13039. Epub 2019 Mar 5. PMID 30734960
• Zhong Y, Zhang Y, Wang Y, Huang R. Maternal antibiotic exposure during pregnancy and the risk of allergic diseases in childhood: A meta-analysis. Pediatr Allergy Immunol. 2021 Apr;32(3):445-456. doi: 10.1111/pai.13411. Epub 2020 Dec 2. PMID 33190323

Идентификаторы

NCT: NCT07532421 · IRB00006761-M20251233 · CON202602149245

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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