Adult-sourced fecal microbiota transplantation ameliorates early-life antibiotic-induced intestinal immune stress in juvenile mice associated with the modulation of the TLR4/MyD88 signaling pathway
- 1Department of Clinical Laboratory, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
- 2Department of Pediatrics, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China
Abstract
Early-life antibiotic (ABX) exposure profoundly disrupts gut microbiota assembly, triggering long-lasting intestinal immune stress. While fecal microbiota transplantation (FMT) is a promising intervention, its immunological and ecological mechanisms in the juvenile gut remain underexplored. In this study, juvenile mice were subjected to a broad-spectrum ABX cocktail for 8 days followed by 4 days of adult-sourced FMT. 16S rRNA sequencing (n = 6/group) revealed that ABX drastically altered the microbial landscape, causing a severe relative reduction of core commensals and an opportunistic expansion of Bacteroides. Subsequent molecular analyses on day 13 (n = 3/group) demonstrated that this dysbiosis significantly upregulated the mucosal TLR4/MyD88 signaling axis and effector cytokines IL-17 and IL-22. Strikingly, adult FMT administration effectively attenuated the TLR4 cascade and reduced pro-inflammatory cytokine transcript levels while immunoregulatory IL-10 transcripts remained partially elevated. Ecologically, FMT did not merely revert the gut to its naive juvenile baseline. Instead, it suppressed Bacteroides overgrowth and established a distinctly new, highly complex community enriched with putative mature, adult-signature taxa such as Parabacteroides, Tannerellaceae, and Desulfobacterota. Interestingly, the downregulation of TLR4 occurred concurrently with the engraftment of these Gram-negative, LPS-bearing taxa. Collectively, adult-sourced FMT ameliorates ABX-induced immune stress not by restoring the original microbiota, but by driving the juvenile gut towards a putatively mature, structurally distinct, and potentially immunologically tolerant ecological state.
Related
- Limosilactobacillus reuteri ameliorates diet-associated metabolic dysfunction in PCOS-like rats: associations with intestinal lipid remodeling and GPR120-related regulation
- Nervonic acid ameliorates high-fat diet-induced obesity and is associated with gut microbiota, fecal metabolic remodeling, and short-chain fatty acid profiles
- Changes in rat intestinal motility and absorption following intestinal transplantation: an experimental study
- Bifidobacterium animalis subsp. lactis BL-99 ameliorates age-related intestinal hypomotility in older adults: a randomized controlled trial
- β-glucosidase-mediated hydrolysis of Ophiocordyceps polysaccharides enhances antioxidant and immunomodulatory activities and ameliorates intestinal barrier function to maintain gut homeostasis
BibTeX
@article{qian2026adultsourced,
title = {{Adult-sourced fecal microbiota transplantation ameliorates early-life antibiotic-induced intestinal immune stress in juvenile mice associated with the modulation of the TLR4/MyD88 signaling pathway}},
author = {Xiang Qian and Yanjing Shen and Xianzhong Luo and Siqin Zhang and Li Wang and Hualin He and Bin Wang},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0359634},
url = {https://doi.org/10.1371/journal.pone.0359634},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Adult-sourced fecal microbiota transplantation ameliorates early-life antibiotic-induced intestinal immune stress in juvenile mice associated with the modulation of the TLR4/MyD88 signaling pathway
AU - Xiang Qian
AU - Yanjing Shen
AU - Xianzhong Luo
AU - Siqin Zhang
AU - Li Wang
AU - Hualin He
AU - Bin Wang
PY - 2026
DA - 2026/10/13
JO - PLOS One
DO - 10.1371/journal.pone.0359634
UR - https://doi.org/10.1371/journal.pone.0359634
AB - Early-life antibiotic (ABX) exposure profoundly disrupts gut microbiota assembly, triggering long-lasting intestinal immune stress. While fecal microbiota transplantation (FMT) is a promising intervention, its immunological and ecological mechanisms in the juvenile gut remain underexplored. In this study, juvenile mice were subjected to a broad-spectrum ABX cocktail for 8 days followed by 4 days of adult-sourced FMT. 16S rRNA sequencing (n = 6/group) revealed that ABX drastically altered the microbial landscape, causing a severe relative reduction of core commensals and an opportunistic expansion of Bacteroides. Subsequent molecular analyses on day 13 (n = 3/group) demonstrated that this dysbiosis significantly upregulated the mucosal TLR4/MyD88 signaling axis and effector cytokines IL-17 and IL-22. Strikingly, adult FMT administration effectively attenuated the TLR4 cascade and reduced pro-inflammatory cytokine transcript levels while immunoregulatory IL-10 transcripts remained partially elevated. Ecologically, FMT did not merely revert the gut to its naive juvenile baseline. Instead, it suppressed Bacteroides overgrowth and established a distinctly new, highly complex community enriched with putative mature, adult-signature taxa such as Parabacteroides, Tannerellaceae, and Desulfobacterota. Interestingly, the downregulation of TLR4 occurred concurrently with the engraftment of these Gram-negative, LPS-bearing taxa. Collectively, adult-sourced FMT ameliorates ABX-induced immune stress not by restoring the original microbiota, but by driving the juvenile gut towards a putatively mature, structurally distinct, and potentially immunologically tolerant ecological state.
SN - 1932-6203
ER -