Press releases

The organization of the intestinal microbiota governed by antibodies

Press release | 03 May 2018 - 17h59 | By INSERM PRESS OFFICE
Immunology, inflammation, infectiology and microbiology

Credits: Fotolia

In a paper published in the journal Science Translational Medicine , Guy and his team Gorochov research center CIMI (Inserm / Université Sorbonne) and Immunology Department at the Pitié-Salpêtrière Hospital, AP-HP, reveal that our IgA act as conductor of the intestinal microbiota.They effectively prevent intestinal colonization by the oral flora and promote the presence of certain bacteria, totally innocent of infectious standpoint, but playing a beneficial role.

Our pact with microbes, otherwise known as symbiosis, we make them indispensable to normal life. Obesity, cancer, autoimmunity, accompanied unlike dysbiosis, that is to say, a disturbance of the bacterial ecosystem in favor of the action of “bad” bacteria. Until recently, the IgA antibodies that we secrete heavily in our digestive tract (66 mg / kg / day) was considered a defense to prevent the passage of potentially harmful bacteria through the intestinal barrier so that its effects potential microbial ecology sheltered by man remained unclear. This is precisely what the researchers wanted to understand.

It is not possible to inactivate a gene in humans to elucidate its function, as is done in mice. To assess the impact of IgA on the microbiota, the authors have taken advantage of a clinical situation of immune deficiency resulting in the almost complete absence of IgA in blood and secretions. Typical bacterial targets of IgA in the general population were also determined by purifying the part of the fecal microbiota naturally covered with IgA in healthy subjects, a unique approach developed by Martin Larsen in the laboratory. Then, total or fractionated microbiota were analyzed in a so-called metagenomic approach comprising sequence simultaneously all bacterial genomes present in a sample. Finally,

The work published today reveals that IgA plays an organizing role of the intestinal microbiota. IgA prevent intestinal colonization by the oral flora while promoting the presence of certain commensal, totally innocent of an infectious standpoint, but play a beneficial role.

This work has also helped to break an old mystery by explaining why the IgA deficiency (affecting about 1 in 500 Caucasian) is not accompanied more often fatal infections. The study shows that IgM, another type of antibody, can partly compensate IgA in its functions of interaction with the microbiota. A compensation however incomplete because patients with IgA deficiency suffer from respiratory infections, but also autoimmunity and atopy. These symptoms although point out the specific roles and not strictly anti-infectives, played by IgA.

These findings were obtained with the help of 21 deficient patients IgA, followed in hospitals of the AP-HP. Besides the fundamental breakthrough in understanding the role of IgA in the establishment of a physiological balance essential to health, the article opens up new therapeutic prospects oral supplementation these IgA deficient patients.

Finally, this study illustrates how anti-microbiota analysis of the antibody response can be a convenient way to study the interface between the host and its microbiota own, and thus the immune footprint of that scale the entire body. The study of anti-microbiota individual serological signatures representing a new biomarker for studying microbiota associations / disease that currently show the open, especially in the field of cancer.

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Press release – Inserm press room The organization of the intestinal microbiota governed by antibodies Link : https://presse.inserm.fr/en/the-organization-of-the-intestinal-microbiota-governed-by-antibodies/31263/
Medias
Researcher Contact

Guy Gorochov

In charge of the team “Immunologie cellulaire et moléculaire des maladies inflammatoires chroniques”

Unité Inserm 1135 Centre d’immunologie et de maladies infectieuses

guy.gorochov@sorbonne-universite.fr

01 42 17 75 07

Press Contact

presse@inserm.fr

Sources

Jehane Fadlallah,1* Hela El Kafsi,1* Delphine Sterlin,1,2 Catherine Juste,3 Christophe Parizot,2 Karim Dorgham,1 Gaëlle Autaa,1 Doriane Gouas,1 Mathieu Almeida,4 Patricia Lepage,3 Nicolas Pons,5 Emmanuelle Le Chatelier,5 Florence Levenez,5 Sean Kennedy,5 Nathalie Galleron,5 Jean-Paul Pais de Barros,6,7 Marion Malphettes,8 Lionel Galicier,8 David Boutboul,8,9 Alexis Mathian,10 Makoto Miyara,1,2 Eric Oksenhendler,8,11 Zahir Amoura,1,10 Joel Doré,3,5 Claire Fieschi,8,9 S. Dusko Ehrlich,5,12 Martin Larsen,1,2†‡ Guy Gorochov 1,2†‡

1Sorbonne Université, INSERM, Centre d’Immunologie et des Maladies Infectieuses–Paris (CIMI-Paris), 75013 Paris, France.

2Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Département d’Immunologie, 75013 Paris, France.

3UMR1319 Micalis, Institut National de la Recherche Agronomique (INRA), Jouy-en-Josas, France. 4Center for Bioinformatics and Computational Biology, University of Maryland, Paint Branch Road, College Park, MD 20742, USA.

5INRA, US1367 MetaGenoPolis, 78350 Jouy en Josas, France.

6INSERM, LNC UMR866, Université Bourgogne Franche-Comté, F-21000 Dijon, France.

7LIPoprotéines et Santé prévention & Traitement des maladies Inflammatoires et du Cancer (LipSTIC) LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France. 8Département d’Immunologie Clinique, Hôpital Saint-Louis, AP-HP, 75010 Paris, France.

9INSERM U1126, Université Paris Diderot Paris 7, 75010 Paris, France.

10Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Service de Médecine Interne 2, Institut E3M, 75013 Paris, France.

11Université Paris Diderot Paris 7, EA3518, 75010 Paris, France.

12King’s College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy’s Hospital, London, UK.

*These authors contributed equally to this work.

†These authors jointly directed this work.

‡Corresponding author. Email: martin.larsen@upmc.fr (M.L.); guy.gorochov@upmc.fr (G.G.)

Sci. Transl. Med. doi.org./10.1126/scitranslmed.aan1217 2 May 2018.

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