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Role of GPR43 receptor in intestinal epithelial cells and neutrophils during gut inflammation

Grant number: 19/14342-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2019
Effective date (End): February 28, 2023
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Marco Aurélio Ramirez Vinolo
Grantee:Patrícia Brito Rodrigues
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:18/15313-8 - Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation, AP.JP2

Abstract

Antibiotic-induced dysbiosis is a key factor to predispose to Clostridium difficile (Cd) infection. Cd colonizes the intestine and triggers intestinal epithelial damage by the action of its toxins A and B and intestinal inflammation. Short-Chain Fatty Acids (SCFAs) are metabolites of the intestinal microbiota from the fermentation of dietary fibers and, as shown in our previous work, protect the intestinal epithelium from damage caused by Cd toxins, as well as attenuate the inflammatory process and the systemic effects of infection. The GPR43 receptor also known as FFAR2 (Free Fatty Acid Receptor-2) is highly expressed in myeloid and intestinal epithelial cells and when activated by SCFAs it regulates important biological activities including immune and intestinal barrier functions. However, the relationship between GPR43 receptor activation in these cells and their role in controlling Cd infection has not been explored. Therefore, our goal is to identify the contribution of tissue-specific GPR43 expression during intestinal inflammation caused by Cd. For this, we will use GPR43-deletion mice in intestinal epithelial cells (VilcreFFAR2fl/fl) or in neutrophils (S100creFFAR2fl/fl), which will be infected with Cd and treated with acetate (FFAR2 linker) or placebo in drinking water; other groups will be treated with diets containing different amounts of soluble fibers with intent of analyze the effect of the endogenous production of SCFAs on the infection. Parameters including mortality, development of Colitis, intestinal barrier and immune response will be evaluated in vivo. In order to complement and deepen our study, we will also perform in vitro analyzes on neutrophils and intestinal organoids isolated from animals deficient or not for FFAR2. With the present project, we will understand the involvement and cell-specific effects of FFAR2 receptor activation, which is relevant not only for a better understanding of the microbial-host interaction, but also, potentially, for the development of new therapeutic strategies. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
High-fiber diet may play a role in controlling the inflammation associated with COVID-19 
Articles published in other media outlets (58 total):
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Al Día (Cuba): Una dieta rica en fibras puede ayudar a controlar la inflamación asociada al COVID-19 (06/May/2021)
Santegra (Rússia): High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (07/Apr/2021)
Catalunya Vanguardista (Espanha): Una dieta rica en fibras contra la inflamación asociada al COVID-19 (06/Apr/2021)
My Pharmacy News: Microbiota-derived molecules do not change the entry or replication of SARS-CoV-2 in intestinal cells (03/Apr/2021)
Archyde: Do High Fiber Diets Help Reduce Inflammation? – healing practice (03/Apr/2021)
Health910: High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (03/Apr/2021)
Bionity (Estônia): High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (01/Apr/2021)
Heilpraxisnet.de (Alemanha): COVID-19: Hilft eine ballaststoffreiche Ernährung die Entzündungen zu reduzieren? (01/Apr/2021)
Environmental News Network (EUA): High-Fiber Diet May Play a Role in Controlling the Inflammation Associated With COVID-19 (31/Mar/2021)
Medical Xpress (Reino Unido): High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (31/Mar/2021)
Panorama Farmacêutico: Dieta rica em fibras pode ter papel no controle de inflamação associada à Covid-19 (31/Mar/2021)
ClinicalNews (EUA): High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (31/Mar/2021)
MDLinx (EUA): High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (31/Mar/2021)
Technologie Média: COVID-19 : un régime riche en fibres contre l’inflammation (31/Mar/2021)
Globe Health News: Microbiota-derived molecules do not change the entry or replication of SARS-CoV-2 in intestinal cells (31/Mar/2021)
Verietyinfo.com: Molecules derived from microbiota do not alter the entry or replication of SARS-CoV-2 in intestinal cells (31/Mar/2021)
The Health News Express: High-fiber weight loss program might play a task in controlling the irritation related to COVID-19 (31/Mar/2021)
The Gary Null Show - Podbean (EUA): High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (31/Mar/2021)
News Medical (Austrália): Microbiota-derived molecules do not change the entry or replication of SARS-CoV-2 in intestinal cells (30/Mar/2021)
Bioengineer (Reino Unido): High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (30/Mar/2021)
Science Codex: High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (30/Mar/2021)
Scienmag Science Magazine (Reino Unido): High-Fiber Diet May Play A Role In Controlling The Inflammation Associated With COVID-19 (30/Mar/2021)
7thSpace: High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (30/Mar/2021)
Healthcare Hygiene Magazine (EUA): High-Fiber Diet May Play Role in Controlling the Inflammation Associated With COVID-19 (30/Mar/2021)
A Closer Look (EUA): High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (30/Mar/2021)
The Uncover Reality (Índia): High-fiber Diet May Play A Role in Controlling The Inflammation Associated With COVID-19 (Food) (30/Mar/2021)
Biotech Asia News (Índia): High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (30/Mar/2021)
iHealthyZone: High-fiber diet may play a role in controlling the inflammation associated with COVID-19 (30/Mar/2021)
Today's Practitioner (EUA): Lab Study: High-fiber Short Chain Fatty Acids May Control COVID-19 Related Gut Tissue Inflammation (30/Mar/2021)
Cofemac: Dieta rica em fibras pode ajudar pacientes com covid (28/Mar/2021)
Portal Correio: Dieta rica em fibras pode ter papel no controle de inflamação associada à Covid-19 (28/Mar/2021)
Rede SIC - Sistema Independente de Comunicação: Dieta rica em fibras pode ter papel no controle da inflamação associada à Covid-19 (17/Mar/2021)
A Cidade On (Campinas, SP): Estudo da Unicamp indica dieta para controle de inflamação associada à covid (09/Mar/2021)
Jornal do Sudoeste : Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (09/Mar/2021)
Folha do ABC online: Dieta rica em fibras pode controlar inflamação associada à Covid (08/Mar/2021)
Blog Jornal da Mulher: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (08/Mar/2021)
A Cidade On (São Carlos, SP): Dieta rica em fibras pode ter papel no controle da inflamação associada à Covid-19 (08/Mar/2021)
Saense: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (08/Mar/2021)
O Estado do Maranhão online: Dieta rica em fibras pode ter papel no controle da inflamação associada à Covid-19 (07/Mar/2021)
Aparecidanet: Dieta rica em fibras pode ajudar no controle da inflamação associada à COVID-19 (07/Mar/2021)
Plantão News (MT): Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (06/Mar/2021)
Meio Norte online (Piauí): Dieta rica em fibras pode ter papel no controle da inflamação da Covid (05/Mar/2021)
Jornal da Unicamp online: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)
UNICAMP - Universidade Estadual de Campinas: Dieta rica em fibras pode ter papel no controle na inflamação associada à Covid-19 (05/Mar/2021)
A Crítica (MS) online: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)
Paranashop: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)
Diário da Saúde: Dieta rica em fibras ajuda a controlar inflamação da covid-19 (05/Mar/2021)
Investe São Paulo: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)
Espaço Ecológico no Ar: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)
Revista Amazônia: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)
Galileu online: Fibras podem ajudar a controlar inflamação intestinal ligada à Covid-19 (05/Mar/2021)
SB 24 horas: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)
Saber Atualizado: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)
Portal da Enfermagem: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)
Refugo: Fibras podem ajudar a controlar inflamação intestinal ligada à Covid-19 (05/Mar/2021)
Quimiweb: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)
Doutor Jairo Bouer: Covid-19: dieta rica em fibras talvez seja útil contra inflamação (05/Mar/2021)
Tubão: Dieta rica em fibras pode ter papel no controle da inflamação associada à COVID-19 (05/Mar/2021)

Scientific publications (8)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FACHI, JOSE LUIS; SECCA, CRISTIANE; RODRIGUES, PATRICIA BRITO; PINHEIRO DE MATO, FELIPE CEZAR; DI LUCCIA, BLANDA; FELIPE, JAQUELINE DE SOUZA; PRAL, LAIS PASSARIELLO; RUNGUE, MARCELLA; ROCHA, VICTOR DE MELO; SATO, FABIO TAKEO; SAMPAIO, ULLIANA; PEDROSA SILVA CLERICI, MARIA TERESA; RODRIGUES, HOSANA GOMES; SARAIVA CAMARA, NIELS OLSEN; CONSONNI, SILVIO ROBERTO; VIEIRA, ANGELICA THOMAZ; OLIVEIRA, SERGIO COSTA; MACKAY, CHARLES REAY; LAYDEN, BRIAN T.; BORTOLUCI, KARINA RAMALHO; COLONNA, MARCO; RAMIREZ VINOLO, MARCO AURELIO. Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2. JOURNAL OF EXPERIMENTAL MEDICINE, v. 217, n. 3 MAR 2020. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.