This scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. We searched the PubMed, Scopus, and Web of Science databases up to March 1, 2025 using a combination of terms related to “asthma or respiratory conditions or wheezing,” “gut microbiota or intestinal flora,” “pregnancy or maternal exposure,” and “epidemiological or population-based studies.” No restrictions were applied regarding publication date or language. Reference lists of eligible studies were also reviewed for additional relevant studies.

All records were imported into EndNote (Clarivate Analytics). After removing duplicates, study selection was conducted in three stages: title screening, abstract review, and full-text evaluation. Two independent reviewers screened each study based on predefined eligibility criteria, with discrepancies resolved through discussion or by a third reviewer.

Studies were included if they met the following criteria: (1) Population-based studies with recruitment of both mothers and children. (2) Exposure assessment was restricted to the period spanning pregnancy through delivery. (3) Stool sample collection and microbial analysis from mothers and/or infants. (4) Documented childhood asthma outcomes or wheezing. (5) Included analysis of mediating role of the gut microbiota.

A total of 1,527 records were initially retrieved from PubMed (n = 147), Scopus (n = 548), and Web of Science (n = 832). After removing 414 duplicates, 1,113 records remained for screening. Following title and abstract screening, 789 were excluded. Subsequently, 324 full-text articles were sought for retrieval and further assessed. Of these, 316 were excluded due to not meeting the eligibility criteria upon full-text review. Ultimately, 8 articles met the inclusion criteria and were included in the present review. The study selection process is illustrated in the PRISMA flow diagram.

Two researchers extracted all the data independently. Each reviewer extracted the following from each study: name of the first authors, publication year, country of study, study aims, study design, study subjects, exposure factors, assessment of child outcomes, covariates and principal results. Disagreements were settled through consensus.

Table 1 presents the detailed data extracted from all included epidemiological studies (N = 8). Based on exposure during pregnancy, the studies were classified into four categories: pet exposure (n = 2), mode of delivery (n = 3), the combined effects of delivery mode and antibiotic exposure (n = 2), and maternal diet during pregnancy (n = 1). All included studies employed a cohort design. Geographically, these studies encompassed diverse populations across three continents. Four were conducted in Europe, specifically, one each in Finland and the Netherlands, and two in Denmark. Three studies originated from North America (United States), and one was conducted in Asia (South Korea). In terms of publication timelines, six were published within the past 5 years, while the remaining two were published in 2011 and 2013. Regarding fecal sample collection, four studies performed a single collection, whereas the other four utilized multiple time points. For outcome assessment, two evaluated wheeze, a common early clinical manifestation of asthma; one assessed early asthma at the age of 0–3 years and asthma at 6–7 years; and the remaining five focused exclusively on asthma aged 6–7 years. The information is depicted on sample collection timing and outcome measurement periods from eight studies (Figure 1), along with a summary of adjusted covariates (Table 2).

Previous epidemiological studies have indicated a potential relationship between maternal pet exposure and the risk of childhood allergic diseases, such as eczema (Eapen et al., 2022), food allergy (Smejda et al., 2020), and asthma (Lodge et al., 2012). Meanwhile, it has been found that pet exposure during the preconception period can influence the human microbiome, thereby exerting a significant influence in programming offspring’s immune system development (Aichbhaumik et al., 2008).

Nermes et al. performed the first study demonstrating that prenatal pet exposure in urban infants was associated with a decreased risk of asthmatic bronchitis and concurrent alterations in gut microbiota composition (Nermes et al., 2013). The study identified two distinct bacterial patterns: Bifidobacterium longum was more abundant in non-asthmatic, pet-exposed infants, whereas Bifidobacterium breve was enriched in asthmatic infants without pet contact. Notably, a potentially important dichotomy in Bifidobacterial effects was identified. Although Bifidobacteria are generally recognized for their anti-inflammatory and immunoregulatory roles (Cukrowska et al., 2020), the study suggests that different species within this genus may exert opposing influences on asthma development.

Another study included in this review showed that prenatal pet exposure correlated with a higher diversity of infant intestinal microbiota, particularly enriched abundances of Collinsella stercoris, Ruminococcus, Lachnospiraceae, and Clostridiaceae (Panzer et al., 2023). Similarly, Ruminococcus levels were found to be elevated in 3–4-month-old infants exposed to furry pets (Tun et al., 2017). Ruminococcus and Clostridium are key gut microbes involved in fermenting complex carbohydrates to produce SCFAs, such as butyrate and propionate (Li et al., 2025; Adjele et al., 2024). These SCFAs support health by strengthening the intestinal barrier and serving as an energy source for epithelial cells (Rowland et al., 2025). Such microbiome–host interactions may regulate immune development and lower the risk of diseases like asthma (Alswat, 2024). However, due to the limited sample size and the relatively short follow-up period of less than 2 years, it remains challenging to determine whether the observed microbial changes associated with pet exposure are implicated in infant allergy outcomes. In addition, the mixed exposure of multiple pets may introduce confounding effects, further complicating the interpretation of results.

Notably, prenatal and postnatal pet exposures often co-occur. Tun et al. found that their co-exposure was associated with more profound microbial alterations compared to prenatal-only exposure (Tun et al., 2017). Specifically, prenatal-only exposure was associated with transient alterations in specific microbial taxa and abundance ratios, whereas sustained exposure was linked to broader and more stable modifications of the gut microbiota, including enrichment of key commensal genera such as Ruminococcus and Oscillospira, as well as the suppression of potentially pathogenic taxa. These findings underscore the necessity of accounting for persistent exposure throuthout prenatal and postnatal period in future research.

With pet ownership on the rise (Kretzler et al., 2022), further research is needed to clarify how different types and timings of pet exposure during pregnancy involve in infant microbiome and influence childhood asthma and allergy risks, and to disentangle the respective and combined effects of prenatal and postnatal exposures through longitudinal designs.

Accumulating studies found that the mode of delivery influences the establishment of the neonatal gut microbiome (Dominguez-Bello et al., 2010). Notably, delivery mode not only alters microbial diversity but also modulates metabolite profiles, both of which exert a crucial role in early immune development (Sarkar et al., 2021). Vaginally delivered infants exhibit higher levels of Gram-negative bacteria and lipopolysaccharide (LPS), a bacterial component that activates immune response. Conversely, cesarean-born infants lack this LPS-mediated immune activation, which may potentially increasing lifelong susceptibility to chronic diseases (Wampach et al., 2018).

Studies included in this review revealed that cesarean delivered infants exhibited reduced levels of Bacteroides and its metabolite sphingosine (Lee-Sarwar et al., 2023). They also showed decreased Bifidobacteria, leading to reduced production of tryptophan metabolites and bile acids (Gürdeniz et al., 2022). And these alterations were associated with an elevated risk of childhood asthma. An earlier study also linked lower fecal Bacteroides levels in infancy to the onset of atopy and wheezing by age five (Arrieta et al., 2018). Sphingosine can be converted into sphingosine-1-phosphate, which has been shown to regulate airway smooth muscle hyperreactivity and proliferation in asthma models (Maguire et al., 2023). In murine studies, Bifidobacterium, as a probiotic, has been shown to modulate lung granulocytes by altering the metabolism of short-chain fatty acids such as tryptophan in the mice intestines (Bezemer et al., 2024), which concurrently alleviated allergic asthma symptoms (Wang et al., 2024). In addition, bile acid metabolites regulate host immune responses by modulating Th17/Tregs balance (Hang et al., 2019). In the study by Gürdeniz et al. (2022), cesarean-born offspring exhibited altered bile acid metabolism and elevated Treg levels. Furthermore, specific components of gut microbiota can modulate immune function, potentially disrupting Th17/Tregs and Th1/Th2 balance (Di Gangi et al., 2020; Irvin et al., 2014), ultimately predisposing individuals to allergic inflammation and asthma (Kotrba et al., 2024).

In terms of multiparous women and delivery methods, previous delivery history holds predictive value for the current delivery mode. Evidence indicates that women with a previous cesarean delivery are more likely to opt for repeat cesarean section. Conversely, multiparous women without a history of cesarean section generally prefer natural childbirth (Ayachi et al., 2016; ACOG, 2019). Moreover, siblings also play a significant role in influcing the development of the infant gut and respiratory tract microbiota. Their influence has been shown to surpass other early-life exposures including mode of delivery, breastfeeding, or antibiotic use. This early microbial enrichment leads to a distinctive “sibling-associated microbiome signature” by age one, which is associated with a reduced risk of asthma by age six (Christensen et al., 2022). Furthermore, birth order has been consistently found to be inversely correlated with allergic disease risk, indicating later-born children tend to have progressively lower risks of developing allergies (Bernsen et al., 2003; Luukkonen et al., 2024). Therefore, whether the mother is a multiparous woman, especially her previous delivery method, and sibling factors should be taken into full account in examing the impact of delivery methods on the infant gut microbiota or the risk of asthma.

Importantly, the impact of delivery mode on early-life microbiota appears to be time-sensitive (Rutayisire et al., 2016) and may also impose effects on subsequent feeding patterns (Prior et al., 2012). Previous studies have shown that cesarean delivery was associated with delayed initiation of breastfeeding, lower rates of exclusive breastfeeding, and an earlier transition to formula feeding (Prior et al., 2012; Alrasheedi, 2023). These changes in early feeding practices may alter the infant gut microbiome, as dietary exposures become the predominant determinants of microbial composition by around 13 weeks of age, with breastfeeding cessation associated with further compositional shifts (Galazzo et al., 2020). Taken together, these interaction between delivery mode, feeding patterns and their temporal dynamics suggest that there are potential critical windows during which delivery mode shapes microbial colonization. Future studies should prioritize longitudinal tracking of delivery mode–related microbial changes, particularly during the first three months of life and the weaning transition.

Epidemiological studies worldwide estimate that 20–30% of women are exposure to antibiotics during pregnancy (Loewen et al., 2018; Chandrakumar et al., 2018). The American College of Obstetricians and Gynecologists recommends routine prophylactic antibiotics before cesarean sections and selective use for vaginal births in high-risk cases (Committee on Practice Bulletins-Obstetrics, 2018). A study indicated limited impact of antibiotic administration during cesarean section on neonatal gut microbiome establishment (Sinha et al., 2024). These findings highlight the need for further investigation into the potential impacts of prenatal/pre-delivery antibiotic use on early microbial programming and the potential health outcomes.

According to Lee et al.’s study, prenatal antibiotic exposure was associated with small airway dysfunction and an increased asthma risk in offspring delivered by cesarean section (Lee et al., 2023). Animal models suggest that imbalanced maternal gut microbiota and reduced SCFAs concentrations may be key mechanisms linking prenatal antibiotic exposure to increased asthma severity in offspring (Alhasan et al., 2020; Alhasan et al., 2023). Butyrate deficiency downregulated type I interferon (IFN-I) signaling in neonatal type 2 innate lymphoid cells (ILC2s), increasing their responsiveness and promoting eosinophil infiltration and ILC2 numbers in the lungs. Changes in breast milk microbiota induced by antibiotics also influenced neonatal ILC2 phenotypes, contributing to offspring asthma development.

While prenatal antibiotics may affect offspring asthma via microbiota alterations, confounding factors especially delivery methods complicate epidemiologic interpretations. Future research should further explore whether antibiotic use at different stages of pregnancy exerts differential effects and emphasize rigorous adjustment for confoundere in study design.

As a key determinant of intestinal flora, maternal diet during pregnancy can influence the composition, diversity, and metabolic activity of the gut microflora (Barrientos et al., 2024). Dietary factors affecting gut microbiota can be categorized into four groups: dietary pattern, food components, vitamins and trace elements, and prebiotics. Changes in any group can profoundly impact gut microbiota and subsequently affect the immune system of both maternal and offspring generations (Hebert et al., 2021; Drall et al., 2020; Sindi et al., 2021). Existing review indicates that a high-fat diet during pregnancy may reduce gut microbial diversity, whereas higher fiber intake appears to be positively associated with it (Maher et al., 2023). In animal models, it has been further demonstrated that a low-fiber diet during pregnancy delayed plasmacytoid dendritic cell (pDC) recruitment and lung Tregs expansion, leading to an increase in lower respiratory tract infections in offspring (Rago et al., 2019). Lee-Sarwar et al. highlighted the pivotal role of SCFAs, particularly acetic acid (Lee-Sarwar et al., 2020), which are primarily produced by the fermentation of dietary fibers in the gut and serve as key mediators linking maternal diet to immune regulation and respiratory health outcomes in offspring (Deleu et al., 2021). In a mouse study, acetate supplementation reduced allergic airway inflammation, airway hyperresponsiveness, and inflammatory cell infiltration, likely by modulating immune responses via G protein-coupled receptors (Thorburn et al., 2015).

Given the long-term implications of maternal diet during pregnancy, future research should further explore differences in dietary patterns and food components, as well as whether the supplementation of vitamins, trace elements, and prebiotics will have more specific effects on the microbiota of both the mother and the offspring, and how microbiota differences affect offspring susceptibility to allergic diseases.

This review has several limitations to consider when interpreting the significance. First, despite a standardized search strategy, the potential omission of relevant studies cannot be excluded. Second, the included studies were categorized into four exposure groups, which could not be unified, limiting comparability. Third, although asthma was uniformly defined as the primary outcome, variations in follow-up duration led to inconsistencies in outcome evaluations. Moreover, substantial heterogeneity in microbial diversity measurements across studies complicated the identification of specific microbiome patterns associated with asthma development. Methodological variations also precluded both a formal quality assessment using standardized tools and a quantitative synthesis of results. In addition, most study populations were composed primarily of individuals of European descent. Only one study explicitly included race or ethnicity as an analytic covariate. These limitations underscore the importance of future studies employing standardized protocols for exposure assessment, outcome measurement, microbiome analysis among diverse populations.