
CLC number:
On-line Access: 2025-10-21
Received: 2024-06-25
Revision Accepted: 2024-08-26
Crosschecked: 2025-10-21
Cited: 0
Clicked: 1860
Citations: Bibtex RefMan EndNote GB/T7714
https://ORCID:orcid.org/0009-0005-6119-574X
https://ORCID:orcid.org/0000-0001-8496-0364
https://ORCID:orcid.org/0000-0003-0429-1645
Cunzheng ZHANG, Ruqiao DUAN, Nini DAI, Yuzhu CHEN, Gaonan LI, Xiao'ang LI, Xiaolin JI, Xuemei ZHONG, Zailing LI, Liping DUAN. Pediatric inflammatory bowel disease in mother‒child pairs: clinical risk factors and gut microbiota characteristics[J]. Journal of Zhejiang University Science B, 2025, 26(10): 995-1014.
@article{title="Pediatric inflammatory bowel disease in mother‒child pairs: clinical risk factors and gut microbiota characteristics",
author="Cunzheng ZHANG, Ruqiao DUAN, Nini DAI, Yuzhu CHEN, Gaonan LI, Xiao'ang LI, Xiaolin JI, Xuemei ZHONG, Zailing LI, Liping DUAN",
journal="Journal of Zhejiang University Science B",
volume="26",
number="10",
pages="995-1014",
year="2025",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2400330"
}
%0 Journal Article
%T Pediatric inflammatory bowel disease in mother‒child pairs: clinical risk factors and gut microbiota characteristics
%A Cunzheng ZHANG
%A Ruqiao DUAN
%A Nini DAI
%A Yuzhu CHEN
%A Gaonan LI
%A Xiao'ang LI
%A Xiaolin JI
%A Xuemei ZHONG
%A Zailing LI
%A Liping DUAN
%J Journal of Zhejiang University SCIENCE B
%V 26
%N 10
%P 995-1014
%@ 1673-1581
%D 2025
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2400330
TY - JOUR
T1 - Pediatric inflammatory bowel disease in mother‒child pairs: clinical risk factors and gut microbiota characteristics
A1 - Cunzheng ZHANG
A1 - Ruqiao DUAN
A1 - Nini DAI
A1 - Yuzhu CHEN
A1 - Gaonan LI
A1 - Xiao'ang LI
A1 - Xiaolin JI
A1 - Xuemei ZHONG
A1 - Zailing LI
A1 - Liping DUAN
J0 - Journal of Zhejiang University Science B
VL - 26
IS - 10
SP - 995
EP - 1014
%@ 1673-1581
Y1 - 2025
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2400330
Abstract: ObjectiveThe risk factors and role of mother-child gut microbiota in pediatric inflammatory bowel disease (PIBD) remain unclear. We aimed to explore the clinical risk factors associated with PIBD, analyze the characteristics of gut microbiota of children and their mothers, and examine the correlation of the microbial composition in mother-child pairs.
MethodsWe conducted a case-control study including children with PIBD and their mothers as the case group, as well as healthy children and their mothers as the control group. Questionnaires were used to collect information such as family illness history and maternal and early-life events. Fecal samples were collected from the children and mothers for microbiota 16S ribosomal RNA (rRNA) sequencing to analyze the composition and its potential association with PIBD.
ResultsA total of 54 pairs of cases and 122 pairs of controls were recruited. A family history of autoimmune disease and antibiotic use during pregnancy were associated with an increased risk of PIBD, and a higher education level of the father was associated with a decreased risk of PIBD. Children with PIBD and mothers exhibited different gut microbiota compared to healthy children and mothers. Similarities were observed in the gut microbiota of mothers and children in the same groups. Some bacterial biomarkers of mothers discovered in this study had the power to predict PIBD in their offspring.
ConclusionsPIBD is influenced by maternal risk factors and has unique gut microbiota characteristics. The mother-child gut microbiota is closely related, suggesting the transmission and influence of the gut microbiota between mothers and children. This study highlights the potential pathogenesis of PIBD and provides a basis for developing targeted interventions.
[1]AgrawalM, SabinoJ, Frias-GomesC, et al., 2021. Early life exposures and the risk of inflammatory bowel disease: systematic review and meta-analyses. EClinicalMedicine, 36:100884.
[2]AgrawalM, PoulsenG, ColombelJF, et al., 2023. Maternal antibiotic exposure during pregnancy and risk of IBD in offspring: a population-based cohort study. Gut, 72(4):804-805.
[3]ArumugamM, RaesJ, PelletierE, et al., 2011. Enterotypes of the human gut microbiome. Nature, 473(7346):174-180.
[4]AsnicarF, ManaraS, ZolfoM, et al., 2017. Studying vertical microbiome transmission from mothers to infants by strain-level metagenomic profiling. mSystems, 2(1):e00164-16.
[5]Baltazar-DíazTA, González-HernándezLA, Aldana-LedesmaJM, et al., 2022. Escherichia/Shigella, SCFAs, and metabolic pathways—the triad that orchestrates intestinal dysbiosis in patients with decompensated alcoholic cirrhosis from western Mexico. Microorganisms, 10(6):1231.
[6]Benítez-PáezA, del PugarEMG, López-AlmelaI, et al., 2020. Depletion of Blautia species in the microbiota of obese children relates to intestinal inflammation and metabolic phenotype worsening. mSystems, 5(2):e00857-19.
[7]BokulichNA, SubramanianS, FaithJJ, et al., 2013. Quality-filtering vastly improves diversity estimates from illumina amplicon sequencing. Nat Methods, 10(1):57-59.
[8]BouhuysM, LexmondWS, van RheenenPF, 2023. Pediatric inflammatory bowel disease. Pediatrics, 151(1):e2022058037.
[9]BuchenauerL, HaangeSB, BauerM, et al., 2023. Maternal exposure of mice to glyphosate induces depression- and anxiety-like behavior in the offspring via alterations of the gut‒brain axis. Sci Total Environ, 905:167034.
[10]ChanJL, WuSG, GeisAL, et al., 2019. Non-toxigenic Bacteroides fragilis (NTBF) administration reduces bacteria-driven chronic colitis and tumor development independent of polysaccharide A. Mucosal Immunol, 12(1):164-177.
[11]ChenHY, TongTY, LuSY, et al., 2023. Urea cycle activation triggered by host-microbiota maladaptation driving colorectal tumorigenesis. Cell Metab, 35(4):651-666.E7.
[12]ChenW, WangDS, DengX, et al., 2024. Bile acid profiling as an effective biomarker for staging in pediatric inflammatory bowel disease. Gut Microbes, 16(1):2323231.
[13]D'AdamoGL, ChonwerawongM, GearingLJ, et al., 2023. Bacterial clade-specific analysis identifies distinct epithelial responses in inflammatory bowel disease. Cell Rep Med, 4(7):101124.
[14]DolingerM, TorresJ, VermeireS, 2024. Crohn’s disease. Lancet, 403(10432):1177-1191.
[15]DongDF, SuTX, ChenW, et al., 2023. Clostridioides difficile aggravates dextran sulfate solution (DSS)-induced colitis by shaping the gut microbiota and promoting neutrophil recruitment. Gut Microbes, 15(1):2192478.
[16]DouglasGM, MaffeiVJ, ZaneveldJR, et al., 2020. PICRUSt2 for prediction of metagenome functions. Nat Biotechnol, 38(6):685-688.
[17]DuanRQ, ZhangCZ, LiGN, et al., 2025. Antibiotic exposure and risk of new-onset inflammatory bowel disease: a systematic review and dose-response meta-analysis. Clin Gastroenterol Hepatol, 23(1):45-58.e15.
[18]EdgarRC, HaasBJ, ClementeJC, et al., 2011. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics, 27(16):2194-2200.
[19]FerrettiP, PasolliE, TettA, et al., 2018. Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host Microbe, 24(1):133-145.e5.
[20]HillCA, CasterlineBW, ValguarneraE, et al., 2024. Bacteroides fragilis toxin expression enables lamina propria niche acquisition in the developing mouse gut. Nat Microbiol, 9(1):85-94.
[21]IwamuroM, TanakaT, KagawaS, et al., 2023. Collagenous colitis in a patient with gastric cancer who underwent chemotherapy. Cureus, 15(5):e39466.
[22]JezernikG, Mičetić-TurkD, PotočnikU, 2020. Molecular genetic architecture of monogenic pediatric IBD differs from complex pediatric and adult IBD. J Pers Med, 10(4):243.
[23]KhorsandB, Asadzadeh AghdaeiH, Nazemalhosseini-MojaradE, et al., 2022. Overrepresentation of Enterobacteriaceae and Escherichia coli is the major gut microbiome signature in Crohn’s disease and ulcerative colitis; a comprehensive metagenomic analysis of IBDMDB datasets. Front Cell Infect Microbiol, 12:1015890.
[24]KorenO, KonnikovaL, BrodinP, et al., 2024. The maternal gut microbiome in pregnancy: implications for the developing immune system. Nat Rev Gastroenterol Hepatol, 21(1):35-45.
[25]KorpelaK, SalonenA, VepsäläinenO, et al., 2018. Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants. Microbiome, 6:182.
[26]KrishnaM, SalakoA, FofanovaT, et al., 2020. Parental education may differentially impact pediatric inflammatory bowel disease phenotype risk. Inflamm Bowel Dis, 26(7):1068-1076.
[27]KuenzigME, FungSG, MarderfeldL, et al., 2022. Twenty-first century trends in the global epidemiology of pediatric-onset inflammatory bowel disease: systematic review. Gastroenterology, 162(4):1147-1159.E4.
[28]le BerreC, HonapS, Peyrin-BirouletL, 2023. Ulcerative colitis. Lancet, 402(10401):571-584.
[29]LeeIA, KambaA, LowD, et al., 2014. Novel methylxanthine derivative-mediated anti-inflammatory effects in inflammatory bowel disease. World J Gastroenterol, 20(5):1127-1138.
[30]LehriB, AtkinsE, ScottTA, et al., 2024. Investigation into the efficiency of diverse N-linking oligosaccharyltransferases for glycoengineering using a standardised cell-free assay. Microb Biotechnol, 17(6):e14480.
[31]LeibovitzhH, LeeSH, XueMY, et al., 2022. Altered gut microbiome composition and function are associated with gut barrier dysfunction in healthy relatives of patients with Crohn’s disease. Gastroenterology, 163(5):1364-1376.E10.
[32]LiCL, ZhangPR, XieYD, et al., 2024. Enterococcus-derived tyramine hijacks α2A-adrenergic receptor in intestinal stem cells to exacerbate colitis. Cell Host Microbe, 32(6):950-963.E8.
[33]LiuH, HongXL, SunTT, et al., 2020. Fusobacterium nucleatum exacerbates colitis by damaging epithelial barriers and inducing aberrant inflammation. J Dig Dis, 21(7):385-398.
[34]LiuXM, MaoBY, GuJY, et al., 2021. Blautia—a new functional genus with potential probiotic properties? Gut Microbes, 13(1):1875796.
[35]MagočT, SalzbergSL, 2011. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics, 27(21):2957-2963.
[36]MariA, KhouryT, AhamadHS, et al., 2020. Autoimmune diseases in first- and second-degree relatives of patients with inflammatory bowel diseases: a case-control survey in Israel. Minerva Med, 111(2):107-14.
[37]MartinoC, DilmoreAH, BurchamZM, et al., 2022. Microbiota succession throughout life from the cradle to the grave. Nat Rev Microbiol, 20(12):707-720.
[38]Mirsepasi-LauridsenHC, VallanceBA, KrogfeltKA, et al., 2019. Escherichia coli pathobionts associated with inflammatory bowel disease. Clin Microbiol Rev, 32(2):e00060-18.
[39]MukherjeeA, LordanC, RossRP, et al., 2020. Gut microbes from the phylogenetically diverse genus Eubacterium and their various contributions to gut health. Gut Microbes, 12(1):1802866.
[40]MukhopadhyaI, HansenR, El-OmarEM, et al., 2012. IBD—what role do proteobacteria play? Nat Rev Gastroenterol Hepatol, 9(4):219-230.
[41]NameirakpamJ, RikhiR, RawatSS, et al., 2020. Genetics on early onset inflammatory bowel disease: an update. Genes Dis, 7(1):93-106.
[42]ÖrtqvistAK, LundholmC, HalfvarsonJ, et al., 2019. Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease: a population-based study. Gut, 68(2):218-225.
[43]PathikkalA, PuthusseriB, DivyaP, et al., 2022. Folate derivatives, 5-methyltetrahydrofolate and 10-formyltetrahydrofolate, protect BEAS-2B cells from high glucose‒induced oxidative stress and inflammation. In Vitro Cell Dev Biol-Anim, 58(5):419-428.
[44]PhamVT, LacroixC, BraeggerCP, et al., 2016. Early colonization of functional groups of microbes in the infant gut. Environ Microbiol, 18(7):2246-2258.
[45]PiovaniD, DaneseS, Peyrin-BirouletL, et al., 2019. Environmental risk factors for inflammatory bowel diseases: an umbrella review of meta-analyses. Gastroenterology, 157(3):647-659.E4.
[46]PittayanonR, LauJT, LeontiadisGI, et al., 2020. Differences in gut microbiota in patients with vs without inflammatory bowel diseases: a systematic review. Gastroenterology, 158(4):930-946.E1.
[47]QiC, ZhouJB, TuHY, et al., 2022. Lactation-dependent vertical transmission of natural probiotics from the mother to the infant gut through breast milk. Food Funct, 13(1):304-315.
[48]QiaoSS, LiuC, SunL, et al., 2022. Gut Parabacteroides merdae protects against cardiovascular damage by enhancing branched-chain amino acid catabolism. Nat Metab, 4(10):1271-1286.
[49]RheeKJ, WuSG, WuXQ, et al., 2009. Induction of persistent colitis by a human commensal, enterotoxigenic Bacteroides fragilis, in wild-type C57BL/6 mice. Infect Immun, 77(4):1708-1718.
[50]SearsCL, GeisAL, HousseauF, 2014. Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J Clin Invest, 124(10):4166-4172.
[51]SegataN, IzardJ, WaldronL, et al., 2011. Metagenomic biomarker discovery and explanation. Genome Biol, 12(6):R60.
[52]ShenhavL, ThompsonM, JosephTA, et al., 2019. FEAST: fast expectation-maximization for microbial source tracking. Nat Methods, 16(7):627-632.
[53]SunXW, ChenZH, YuL, et al., 2023. Bacteroides dorei BDX-01 alleviates DSS-induced experimental colitis in mice by regulating intestinal bile salt hydrolase activity and the FXR-NLRP3 signaling pathway. Front Pharmacol, 14:1205323.
[54]SunY, XieRX, LiL, et al., 2021. Prenatal maternal stress exacerbates experimental colitis of offspring in adulthood. Front Immunol, 12:700995.
[55]TianM, LiQH, ZhengTH, et al., 2023. Maternal microbe-specific modulation of the offspring microbiome and development during pregnancy and lactation. Gut Microbes, 15(1):2206505.
[56]Valles-ColomerM, Blanco-MíguezA, ManghiP, et al., 2023. The person-to-person transmission landscape of the gut and oral microbiomes. Nature, 614(7946):125-135.
[57]VelosaM, HochnerH, YerushalmiB, et al., 2022. Pre- and perinatal factors predicting inflammatory bowel disease: a population-based study with fifty years of follow-up. J Crohns Colitis, 16(9):1397-1404.
[58]WangSP, RyanCA, BoyavalP, et al., 2020. Maternal vertical transmission affecting early-life microbiota development. Trends Microbiol, 28(1):28-45.
[59]WangQZ, DengZT, LanJ, et al., 2022. Inhibition of GABAAR or application of Lactobacillus casei Zhang alleviates ulcerative colitis in mice: GABAAR as a potential target for intestinal epithelial renewal and repair. Int J Mol Sci, 23(19):11210.
[60]WangXQ, XiaoY, XuX, et al., 2021. Characteristics of fecal microbiota and machine learning strategy for fecal invasive biomarkers in pediatric inflammatory bowel disease. Front Cell Infect Microbiol, 11:711884.
[61]XiaoLW, ZhaoFQ, 2023. Microbial transmission, colonisation and succession: from pregnancy to infancy. Gut, 72(4):772-786.
[62]ZhaoJ, BaiM, NingXX, et al., 2022. Expansion of Escherichia-Shigella in gut is associated with the onset and response to immunosuppressive therapy of IgA nephropathy. J Am Soc Nephrol, 33(12):2276-2292.
Open peer comments: Debate/Discuss/Question/Opinion
<1>