Indole-3-carbinol and chlorogenic acid combination modulates gut microbiome and attenuates nonalcoholic steatohepatitis in a murine model

Autor(es)

Bacil, Gabriel P. ; Romualdo, Guilherme R. ; Rodrigues, Josias ; Barbisan, Luis F.

• Tipo de documento: Artigo Científico
• Fonte: Food Research International; v. 174, p. 11-pg., 2023-10-05.

Resumo

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, affecting almost 32% of the population and ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Recent findings indicate that the fast-growing prevalence of NAFLD might be linked to adherence to a Westernized diet (WD), mostly composed of fat/sugar-enriched foods. The WD has been reportedly targeted as a potential driver of gut liver axis unbalance, suggesting a major role in NASH. On the other hand, bioactive food compounds feature as a potential chemopreventive strategy against NASH, due to their beneficial effects (i.e, anti-inflammatory/oxidant activity and modulation of gut microbiome). Brassicaceae vegetables are known for their high amount of isothiocyanates and polyphenols, as indole-3-carbinol (I3C) and chlorogenic acid (CGA). Thus, we sought to assess the effects of human relevant doses of I3C and CGA isolated or in combination (5/125 mg/Kg of body weight, respectively) on a diet/chemical-induced murine model of NASH. I3C + CGA oral treatment diminished NAFLD activity score (NAS) (p < 0.0001), as well as alleviated the hepatic lipid (p = 0.0011) accumulation, prevented hepatic stellate cell (HSC) activation (p < 0.0001), and subsequent fibrosis (p < 0.0001). The combination also reduced the number of both hepatic CD68-positive macrophages (p < 0.0001) and cleaved caspase-3 hepatocytes (p < 0.0001) and diminished the malondialdehyde levels (p = 0.0155). Additionally, the combination of I3C + CGA restored the relative abundance of Alistipes (p = 0.0299), Allobaculum (p = 0.0014), Bacteroides (p = 0.0046), and Odoribacter (p = 0.0030) bacteria genera on the gut microbiome. Taken together, these findings show that the combination of I3C + CGA at populational-relevant ingestion, rather than the I3C or CGA alone, was able to modulate gut microbiome and attenuate NASH in this hybrid model mouse. (AU)

• Processo FAPESP: 20/01944-6 - Ácido clorogênico e indol-3-carbinol: efeito de compostos de vegetais Brassica sobre a esteatohepatite não alcoólica in vivo
• Beneficiário: Gabriel Bacil Prata
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 20/01078-7 - Implicações do glifosato e do 2,4-D sobre a doença hepática gordurosa não alcoólica in vivo: análise do transcriptoma e da microbiota
• Beneficiário: Luís Fernando Barbisan
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/00377-0 - Efeitos da exposição aos herbicidas glifosato e 2,4-D sobre a esteatohepatite não-alcoólica em camundongos: Insights sobre exposições contemporâneas?
• Beneficiário: Guilherme Ribeiro Romualdo
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/16972-5 - Modulação do microbioma do intestino de portadores de retocolite ulcerativa através de transplantação fecal: um estudo controlado, duplo cego e randomizado
• Beneficiário: Josias Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Regular