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

NCT07532421 | Not Yet Recruiting

• 2 other identifiers: IRB00006761-M20251233CON202602149245
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Antibiotic; Allergic Diseases; Infants; Probiotic

Keywords

probiotics; infants; early postnatal antibiotic exposure; allergic diseases

Outcome Measures

Primary Outcomes (3)

• Incidence of allergic diseases in infants

  Compare the incidence of allergic diseases between the antibiotic-exposed group and the control group, and analyze the effects of antibiotic exposure intensity, frequency, and type on the development of allergic diseases. Furthermore, compare the incidence of allergic diseases among the probiotic intervention group, the placebo group, and the control group.

  Follow up until the enrolled infants reach 1 year of age.

• Changes in gut microbiota composition in the antibiotic-exposed group

  Compare the changes in gut microbiota composition of infants in the antibiotic-exposed group at enrollment (1 month of age) and at 3, 6, and 12 months of age, compare the differences in gut microbiota composition among the three groups, and analyze the effect of antibiotic exposure intensity on gut microbiota composition.

  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

  Compare the changes in fecal metabolites between the probiotic intervention group and the placebo group, and explore the potential mechanisms by which specific probiotic intervention induces alterations in gut metabolites.

  At 3, 6, and 12 months of age

Secondary Outcomes (2)

• Growth curves of infants in the antibiotic-exposed group and the control group

  At 3, 6, 9, and 12 months of age.

• Proportion of infectious diseases in infants of the antibiotic-exposed group and the control group

  Follow up until the infant reaches 1 year of age.

Study Arms (3)

Control group

NO INTERVENTION

The control group consists of full-term healthy newborns who have not received antibiotics within 30 days after birth. No intervention will be given; they will only be followed up for the occurrence of allergic diseases and infectious diseases within the first year of life. During the follow-up period, four stool samples will be collected for the analysis of gut microbiota and their metabolites.

Probiotic intervention group

EXPERIMENTAL

The probiotic intervention group will recruit full-term newborns who have received antibiotics within 30 days after birth. Starting at 5 weeks of age, they will receive an 8-week course of an oral probiotic mixture (containing Bifidobacterium longum subsp. infantis R0033, Lactobacillus helveticus R0052, and Bifidobacterium bifidum R0071). They will be followed up for the occurrence of allergic diseases and infectious diseases within the first year of life. During the follow-up period, four stool samples will be collected for the analysis of gut microbiota and their metabolites.

Dietary Supplement: Probiotic mixture

Placebo group

PLACEBO COMPARATOR

The placebo group will recruit full-term newborns who have received antibiotics within 30 days after birth. Starting at 5 weeks of age, they will receive an 8-week course of an oral placebo without the probiotic. They will be followed up for the occurrence of allergic diseases and infectious diseases within the first year of life. During the follow-up period, four stool samples will be collected for the analysis of gut microbiota and their metabolites.

Other: Placebo

Interventions

Placebo OTHER

Oral a placebo without probiotics for 8 weeks, once daily, one sachet per day.

Placebo group

Probiotic mixture DIETARY_SUPPLEMENT

Oral probiotic mixture for 8 weeks, once daily, one sachet per day

Probiotic intervention group

Eligibility Criteria

• Age: 1 Day - 35 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University Third Hospital: lead

Study Sites (1)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

Related Publications (9)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Li M, Lu ZK, Amrol DJ, Mann JR, Hardin JW, Yuan J, Cox CL, Love BL. Antibiotic Exposure and the Risk of Food Allergy: Evidence in the US Medicaid Pediatric Population. J Allergy Clin Immunol Pract. 2019 Feb;7(2):492-499. doi: 10.1016/j.jaip.2018.09.036. Epub 2018 Nov 20.

  PMID: 30468878 BACKGROUND

• 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):1341-1348.e5. doi: 10.1016/j.jaip.2019.11.040. Epub 2019 Dec 14.

  PMID: 31846795 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Ren HL, Sun JL, Liu G. [Comorbidity and multimorbidity for allergic diseases]. Zhonghua Yu Fang Yi Xue Za Zhi. 2022 Jun 6;56(6):735-739. doi: 10.3760/cma.j.cn112150-20220312-00229. Chinese.

  PMID: 35785854 BACKGROUND

Central Study Contacts

Juan Zhang, Medical Doctor

CONTACT

+8615611968716; arbooo@126.com

Nini Dai, Medical Doctor

CONTACT

+8618801120799; 1445693658@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2026
• First Posted: April 15, 2026
• Study Start: April 17, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)