Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery
Abstract Background Most interactions between the host and its microbiota occur at the gut barrier, and primary colonizers are essential in the gut barrier maturation in the early life. The mother–offspring transmission of microorganisms is the most important factor influencing microbial colonizatio...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Microbiome |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40168-023-01584-0 |
| _version_ | 1797557821969006592 |
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| author | M. Barone Y. Ramayo-Caldas J. Estellé K. Tambosco S. Chadi F. Maillard M. Gallopin J. Planchais F. Chain C. Kropp D. Rios-Covian H. Sokol P. Brigidi P. Langella R. Martín |
| author_facet | M. Barone Y. Ramayo-Caldas J. Estellé K. Tambosco S. Chadi F. Maillard M. Gallopin J. Planchais F. Chain C. Kropp D. Rios-Covian H. Sokol P. Brigidi P. Langella R. Martín |
| author_sort | M. Barone |
| collection | DOAJ |
| description | Abstract Background Most interactions between the host and its microbiota occur at the gut barrier, and primary colonizers are essential in the gut barrier maturation in the early life. The mother–offspring transmission of microorganisms is the most important factor influencing microbial colonization in mammals, and C-section delivery (CSD) is an important disruptive factor of this transfer. Recently, the deregulation of symbiotic host-microbe interactions in early life has been shown to alter the maturation of the immune system, predisposing the host to gut barrier dysfunction and inflammation. The main goal of this study is to decipher the role of the early-life gut microbiota-barrier alterations and its links with later-life risks of intestinal inflammation in a murine model of CSD. Results The higher sensitivity to chemically induced inflammation in CSD mice is related to excessive exposure to a too diverse microbiota too early in life. This early microbial stimulus has short-term consequences on the host homeostasis. It switches the pup’s immune response to an inflammatory context and alters the epithelium structure and the mucus-producing cells, disrupting gut homeostasis. This presence of a too diverse microbiota in the very early life involves a disproportionate short-chain fatty acids ratio and an excessive antigen exposure across the vulnerable gut barrier in the first days of life, before the gut closure. Besides, as shown by microbiota transfer experiments, the microbiota is causal in the high sensitivity of CSD mice to chemical-induced colitis and in most of the phenotypical parameters found altered in early life. Finally, supplementation with lactobacilli, the main bacterial group impacted by CSD in mice, reverts the higher sensitivity to inflammation in ex-germ-free mice colonized by CSD pups’ microbiota. Conclusions Early-life gut microbiota-host crosstalk alterations related to CSD could be the linchpin behind the phenotypic effects that lead to increased susceptibility to an induced inflammation later in life in mice. Video Abstract |
| first_indexed | 2024-03-10T17:21:37Z |
| format | Article |
| id | doaj.art-9bc254305ed4404096c3dd3611458fd4 |
| institution | Directory Open Access Journal |
| issn | 2049-2618 |
| language | English |
| last_indexed | 2024-03-10T17:21:37Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj.art-9bc254305ed4404096c3dd3611458fd42023-11-20T10:19:25ZengBMCMicrobiome2049-26182023-07-0111112410.1186/s40168-023-01584-0Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section deliveryM. Barone0Y. Ramayo-Caldas1J. Estellé2K. Tambosco3S. Chadi4F. Maillard5M. Gallopin6J. Planchais7F. Chain8C. Kropp9D. Rios-Covian10H. Sokol11P. Brigidi12P. Langella13R. Martín14Microbiomics Unit, Department of Medical and Surgical Sciences, University of BolognaINRAE, AgroParisTech, GABI, Paris-Saclay UniversityINRAE, AgroParisTech, GABI, Paris-Saclay UniversityINRAE, AgroParisTech, Micalis Institut,, Paris-Saclay UniversityINRAE, AgroParisTech, Micalis Institut,, Paris-Saclay UniversityINRAE, AgroParisTech, Micalis Institut,, Paris-Saclay UniversityCNRS, CEA, l’Institut de Biologie Intégrative de La Cellule (I2BC), Paris-Saclay UniversityINRAE, AgroParisTech, Micalis Institut,, Paris-Saclay UniversityINRAE, AgroParisTech, Micalis Institut,, Paris-Saclay UniversityINRAE, AgroParisTech, Micalis Institut,, Paris-Saclay UniversityINRAE, AgroParisTech, Micalis Institut,, Paris-Saclay UniversityINRAE, AgroParisTech, Micalis Institut,, Paris-Saclay UniversityMicrobiomics Unit, Department of Medical and Surgical Sciences, University of BolognaINRAE, AgroParisTech, Micalis Institut,, Paris-Saclay UniversityINRAE, AgroParisTech, Micalis Institut,, Paris-Saclay UniversityAbstract Background Most interactions between the host and its microbiota occur at the gut barrier, and primary colonizers are essential in the gut barrier maturation in the early life. The mother–offspring transmission of microorganisms is the most important factor influencing microbial colonization in mammals, and C-section delivery (CSD) is an important disruptive factor of this transfer. Recently, the deregulation of symbiotic host-microbe interactions in early life has been shown to alter the maturation of the immune system, predisposing the host to gut barrier dysfunction and inflammation. The main goal of this study is to decipher the role of the early-life gut microbiota-barrier alterations and its links with later-life risks of intestinal inflammation in a murine model of CSD. Results The higher sensitivity to chemically induced inflammation in CSD mice is related to excessive exposure to a too diverse microbiota too early in life. This early microbial stimulus has short-term consequences on the host homeostasis. It switches the pup’s immune response to an inflammatory context and alters the epithelium structure and the mucus-producing cells, disrupting gut homeostasis. This presence of a too diverse microbiota in the very early life involves a disproportionate short-chain fatty acids ratio and an excessive antigen exposure across the vulnerable gut barrier in the first days of life, before the gut closure. Besides, as shown by microbiota transfer experiments, the microbiota is causal in the high sensitivity of CSD mice to chemical-induced colitis and in most of the phenotypical parameters found altered in early life. Finally, supplementation with lactobacilli, the main bacterial group impacted by CSD in mice, reverts the higher sensitivity to inflammation in ex-germ-free mice colonized by CSD pups’ microbiota. Conclusions Early-life gut microbiota-host crosstalk alterations related to CSD could be the linchpin behind the phenotypic effects that lead to increased susceptibility to an induced inflammation later in life in mice. Video Abstracthttps://doi.org/10.1186/s40168-023-01584-0C-section deliveryMicrobiotaPrimary colonizationEarly lifeInflammationGut barrier |
| spellingShingle | M. Barone Y. Ramayo-Caldas J. Estellé K. Tambosco S. Chadi F. Maillard M. Gallopin J. Planchais F. Chain C. Kropp D. Rios-Covian H. Sokol P. Brigidi P. Langella R. Martín Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery Microbiome C-section delivery Microbiota Primary colonization Early life Inflammation Gut barrier |
| title | Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery |
| title_full | Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery |
| title_fullStr | Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery |
| title_full_unstemmed | Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery |
| title_short | Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery |
| title_sort | gut barrier microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of c section delivery |
| topic | C-section delivery Microbiota Primary colonization Early life Inflammation Gut barrier |
| url | https://doi.org/10.1186/s40168-023-01584-0 |
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