Assessment of the influences of the microbiome and histidine metabolism on the effects of nicotinamide riboside on glycemic control in the context of obesity

• Grant number: 24/07895-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: November 01, 2024
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Raul Gobato da Costa
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/08354-2 - The interplay between the immune system and metabolism as a key determinant of the aging process, AP.TEM

Abstract

The relationship between nutrition, the gut, and the microbiota has been the subject of intensestudy in recent decades. The imbalance between these relationships is associated with theincidence of various metabolic diseases, which have been increasing worldwide. Changes indietary patterns towards a Western-type of diet are linked to a condition of intestinal dysbiosis,where alterations in microbial metabolism and increased incidence of specific microorganismspromote adiposity in animals and humans. Nicotinamide riboside (NR), a natural compound ofthe vitamin B3 family found in various foods and a precursor to NAD+, has been used in animalmodels with the aim of promoting metabolic health and longevity. However, our group hasidentified that NR administration increases the levels of the microbial metabolite imidazolepropionate (IMID) in rodents and humans. IMID is a product of microbial histidine metabolismand its production is associated with the microbiota of patients with type 2 diabetes, exerting adiabetogenic action. Consistently, changes in dietary histidine levels have been associated withmetabolic effects in obesity models, respectively. Thus, we propose the hypothesis that thepotential beneficial effects of NR are masked or mitigated by the production of IMID by themicrobiota. In this case, when exposed to a histidine-poor diet or subjected to antibiotictreatment for microbiota depletion, we expect obese mice to benefit positively from NRtreatment, showing improvements in glycemic homeostasis not necessarily observed in controlobese mice. With this, we aim to unravel possible nutritional interactions that aim to promote thebeneficial effects of dietary supplements.