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Investigation of the molecular mechanisms involved in the interaction between microbiota-derived metabolites and host cells during inflammation

Grant number: 18/15313-8
Support type:Research Grants - Young Investigators Grants- Phase 2
Duration: May 01, 2019 - April 30, 2024
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal researcher:Marco Aurélio Ramirez Vinolo
Grantee:Marco Aurélio Ramirez Vinolo
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:12/10653-9 - Role of short chain fatty acids and their receptor (GPR43) in the immune response to anaerobic bacteria in vivo and in vitro, AP.JP
Associated grant(s):20/04583-4 - Impact of intestinal microbiota and its metabolites on SARS-CoV-2 infection, AP.R
Associated scholarship(s):20/00311-0 - Role of SMARCAD-1 protein in macrophage function and microbiota-host interactions, BP.DD
20/02919-5 - Relevance of the FFAR2 receptor on the biological responses of stem cells and Intestinal Epithelial Cells (IECs) during inflammatory conditions, BP.PD
20/02685-4 - Investigation of the effect of gut dysbiosis on histone post-translational modifications in neutrophils, BP.PD
+ associated scholarships 20/00465-7 - Relevance of SCFAs-induced histone acylation in neutrophils production of inflammatory mediators, BP.DD
20/02312-3 - Study of the effect of short-chain fatty acids on the tissue regeneration process during experimental colitis, BP.DD
19/14342-7 - Role of GPR43 receptor in intestinal epithelial cells and neutrophils during gut inflammation, BP.DR
19/11662-0 - Participation of the FFAR2 receptor in the inflammation in a DSS-induced colitis model, BP.MS - associated scholarships

Abstract

How the microbiota communicates with the host and contributes to health is a key question for progress in this research field. Bacterial metabolites called short chain fatty acids (SCFAs), which are generated by fermentation of non-digestible carbohydrates, constitute a link between microbiota and host cells. Previous studies demonstrated that these metabolites regulate host metabolism and immunity. However, the molecular mechanisms are not totally defined. The aim of this project is to investigate this by examining 1) activation of the SCFA receptor FFAR2 (GPR43) and 2) modification of the pattern of histone acylations (mainly, acetylation and crotonylation) in neutrophils and intestinal epithelial cells (IECs) and their biological relevance in inflammatory models. For this, we will 1) characterize, using cell-specific knockout mice, the role of FFAR2 in neutrophil and IEC functions, and its participation in inflammasome activation and relevance during intestinal inflammation and; 2) investigate the effect of SCFAs on the pattern of histone acylation in intestinal epithelial cells and neutrophils and how this affects their transcriptional and effector responses during inflammation. With this, we will contribute to the understanding of the molecular mechanisms of microbial-host interaction and identification of new biomarkers and therapeutic targets for inflammatory diseases. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Drug attenuates weight gain in animals fed a high-fat diet  
Una dieta rica en fibras puede cumplir un papel en el control de la inflamación asociada al COVID-19  
High-fiber diet may play a role in controlling the inflammation associated with COVID-19 
Fármaco atenua o ganho de peso em animais alimentados com dieta rica em gordura 
Articles published in other media outlets (90 total):
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UOL: Fármaco ameniza ganho de peso em animais aliado a dieta rica em gordura (02/Dec/2020)
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)
Santé blog (França): OBÉSITÉ: Le médicament thermogénique qui brûle les adipocytes (23/Dec/2020)
ICTQ - Instituto de Ciência, Tecnologia e Qualidade: Pesquisadores da Unicamp estudam eficácia de antibiótico contra obesidade (22/Dec/2020)
Planeta online: Remédio reduz ganho de peso em animais com dieta rica em gordura (14/Dec/2020)
Blueedit.cn (China): 揭示依诺沙星通过调节脂肪组织miRNA表达 (11/Dec/2020)
SOHU.com (China): Science子刊详解!揭示依诺沙星通过调节脂肪组织miRNA表达,诱导氧化代谢和降低体重增加 (06/Dec/2020)
Bioon.com (China): Science子刊详解!揭示依诺沙星通过调节脂肪组织miRNA表达,诱导氧化代谢和降低体重增加 (06/Dec/2020)
Plantão News (MT): Fármaco atenua o ganho de peso em animais alimentados com dieta rica em gordura (05/Dec/2020)
Healthcare Hygiene Magazine (EUA): Antibacterial Drug Alters MicroRNA Production to Boost Thermogenesis, Reduce Weight Gain in Mice (05/Dec/2020)
Deenewsline (Nigéria): Drug attenuates weight gain in animals fed a high-fat diet (05/Dec/2020)
Genetic Engineering & Biotechnology News (EUA): Antibacterial Drug Alters MicroRNA Production to Boost Thermogenesis, Reduce Weight Gain in Mice (04/Dec/2020)
Revista Amazônia: Fármaco atenua o ganho de peso em animais alimentados com dieta rica em gordura (04/Dec/2020)
Medical Xpress (Reino Unido): 药物可减轻高脂饮食动物的体重增加 - Medicamentos podem reduzir o ganho de peso em animais de dieta rica em gordura (03/Dec/2020)
Medindia (Índia): Drug Reduces Weight Gain in Mice Fed a High-fat Diet (03/Dec/2020)
Hale Plus Hearty (Nigéria): Drug attenuates weight gain in animals fed a high-fat diet (03/Dec/2020)
Portal da Enfermagem: Fármaco atenua o ganho de peso em animais alimentados com dieta rica em gordura (03/Dec/2020)
MT HOJE: Fármaco atenua o ganho de peso em animais alimentados com dieta rica em gordura (03/Dec/2020)
7thSpace: Drug attenuates weight gain in animals fed a high-fat diet (03/Dec/2020)
Mindzilla (Reino Unido): 5 min read Drug Attenuates Weight Gain in Animals Fed a High-Fat Diet (03/Dec/2020)
Sochob - Sociedad Chilena de Obesidad (Chile): FÁRMACO ATENÚA EL AUMENTO DE PESO EN ANIMALES ALIMENTADOS CON UNA DIETA RICA EN GRASAS (03/Dec/2020)
AZo Life Sciences: Drug meant for bacterial infections can combat weight gain (03/Dec/2020)
HealthyPhotonn: Drug attenuates weight gain in animals fed a high-fat diet (03/Dec/2020)
Technology Times (Paquistão): Drug Reduces Weight Gain In Mice Fed A High-Fat Diet (03/Dec/2020)
Wheight Control (EUA): Experimental Antibiotic May Boost Metabolism and Mitigate Obesity (03/Dec/2020)
Medical Xpress (Reino Unido): Drug attenuates weight gain in animals fed a high-fat diet (02/Dec/2020)
Science Codex: Drug attenuates weight gain in animals fed a high-fat diet (02/Dec/2020)
Technology Networks (Reino Unido): Drug Reduces Weight Gain in Mice Fed a High-Fat Diet (02/Dec/2020)
Scienmag Science Magazine (Reino Unido): Drug attenuates weight gain in animals fed a high-fat diet (02/Dec/2020)
Drug Target Review (Reino Unido): Drug target to tackle COVID-19 inflammatory processes identified (02/Dec/2020)
Ethical Editor EUA): Drug attenuates weight gain in animals fed a high-fat diet (02/Dec/2020)
Goalshakers (Reino Unido): Drug attenuates weight gain in animals fed a high-fat diet (02/Dec/2020)
Postin Trend: Drug attenuates weight gain in animals fed a high-fat diet (02/Dec/2020)

Scientific publications
(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, J. L.; PRAL, L. P.; DOS SANTOS, J. A. C.; CODO, A. C.; DE OLIVEIRA, S.; FELIPE, J. S.; ZAMBOM, F. F. F.; CAMARA, N. O. S.; VIEIRA, P. M. M. M.; COLONNA, M.; VINOLO, M. A. R. Hypoxia enhances ILC3 responses through HIF-1 alpha-dependent mechanism. MUCOSAL IMMUNOLOGY, JAN 2021. Web of Science Citations: 0.
ROCHA, ANDREA LIVIA; DE LIMA, TANES IMAMURA; DE SOUZA, GERSON PROFETA; CORREA, RENAN OLIVEIRA; FERRUCCI, DANILO LOPES; RODRIGUES, BRUNO; LOPES-RAMOS, CAMILA; NILSSON, DANIEL; KNITTEL, THIAGO LEITE; CASTRO, POLLYANA RIBEIRO; FERNANDES, MARIANE FONT; MARTINS, FLAVIANO DOS SANTOS; PARMIGIANI, RAPHAEL BESSA; SILVEIRA, LEONARDO REIS; CARVALHO, HERNANDES F.; AUWERX, JOHAN; VINOLO, MARCO AURELIO R.; BOUCHER, JEREMIE; MORI, MARCELO A. Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression. SCIENCE ADVANCES, v. 6, n. 49 DEC 2020. Web of Science Citations: 0.
SATO, FABIO TAKEO; YAP, YU ANNE; CRISMA, AMANDA RABELLO; PORTOVEDO, MARIANA; MURATA, GILSON MASAHIRO; HIRABARA, SANDRO MASSAO; RIBEIRO, WILLIAN RODRIGUES; FERREIRA, CAROLINE MARCANTONIO; CRUZ, MAYSA MARIANA; BERTAGLIA PEREIRA, JOICE NAIARA; PAYOLLA, TANYARA BALIANI; SATO GUIMA, SUZANA EIKO; THOMAS, ANDREW MALTEZ; SETUBAL, JOAO CARLOS; CARDOSO ALONSO-VALE, MARIA ISABEL; SANTOS, MARINILCE FAGUNDES; CURI, RUI; MARINO, ELIANA; VINOLO, MARCO A. R. Tributyrin Attenuates Metabolic and Inflammatory Changes Associated with Obesity through a GPR109A-Dependent Mechanism. CELLS, v. 9, n. 9 SEP 2020. Web of Science Citations: 0.

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