Disponible en Dadun la tesis «Study of novel probiotics for the treatment of obesity and metabolic syndrome» de Ignacio Goyache.

Resumen: Gut microbiota has emerged as a critical modulator of host metabolism, inflammation, and energy balance, with increasing evidence linking its dysregulation (dysbiosis) to the development of obesity and metabolic syndrome. In this context, probiotics and their inactivated forms (postbiotics) offer a promising therapeutic strategy to counteract these diseases. This work investigates the anti-obesity, anti-inflammatory, and metabolic regulatory effects of three novel probiotic strain Latilactobacillus sakei CNTA 173, Lactiplantibacillus plantarum CNTA 628 and COmpanilactibacillus alimentarius CNTA 209 in various in vivo models, including Caenorhabditis elegans, Wistar rats, Danio rerio, and C57BL/6 mice. In Chapter 1, probiotics demonstrated lipid-lowering and lifespan extending effects in C. elegans, modulating genes involved in lipid and carbohydrate metabolism, insulin signalling, and β-oxidation pathways. Chapter 2 explores the probiotic’s effects in a diet-induced obese Wistar rat model, where L. sakei CNTA 173 improved glucose tolerance, reduced inflammation and visceral adiposity, altered mesenteric fat gene expression, and influenced sphingolipid and ceramide metabolism. 16S metagenomics analysis confirmed the presence of the probiotic DNA in faecal samples and revealed correlations between its abundance and improvements in metabolic parameters. Moreover, a toxicological study stablished the dose of 109 CFU/ day as the NOAEL. Chapter 3 further evaluates L. sakei CNTA 173 in a diet- induced obesity zebrafish model, where the strain significantly prevented weight gain, ameliorated hepatic steatosis, and modulated gut microbiota composition and gene expression. In Chapter 4, postbiotic forms of L. sakei CNTA 173, especially heat-inactivated L. sakei, exhibited superior effectiveness in reducing body weight gain, improving glycaemic and lipid profiles, and attenuating hepatic fat accumulation in C57BL/6 mice. All forms modulated gene expression in brown adipose tissue and modulated gut microbiota distribution, increasing beneficial bacteria and restoring eubiosis. Together, the findings support the anti-obesogenic potential of L. sakei CNTA 173 and its postbiotic forms across multiple obesity animal models. The strain modulates key metabolic and inflammatory pathways, enhances gut microbiota diversity, and may serve as a novel microbiota-targeted intervention for obesity and related comorbidities. Moreover, this work validates the use of C. elegans, zebrafish, rats, and mice as complementary in vivo platforms to study probiotic efficacy and mechanism of action.

La tesis ha sido defendida en mayo de 2025 y ha sido dirigida por Paula Aranaz-Oroz y Fermín Milagro-Yoldi.