Metabolic imprint after immunological scar induced by acute gastrointestinal infection

Author(s)

Mirian Krystel De Siqueira

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2019-08-05

Examining board members

Denise Morais Fonseca; William Tadeu Lara Festuccia; Marco Aurélio Ramirez Vinolo

• Advisor: Denise Morais Fonseca

Abstract

Infections at barrier tissues such as the skin, lungs and gut, represent a frequent occurrence worldwide. However, the mechanisms underlying the long-term consequences of acute episodes of infection for host physiology remain poorly explored. In particular, infection at the gut mucosa can change microbiota composition and interfere in the way of how the host responds to environmental challenges, including changes in diet and pathogen exposure. Here, we report how a defined episode of acute intestinal infection can change host physiology and contribute for improved metabolism and environmental advantage. Following the clearance of Yersinia pseudotuberculosis (YP) infection, we found a persistent low-grade production of TNF, IL-1beta and IL-6 in several white adipose tissue (AT) compartments. This chronic inflammation was associated with increased permeability of intestinal lymphatics and chylomicron leakage. Despite the severe loss of dietary lipids, mice presented increased weight gain and a persistent remodeling of the white adipose tissue depots. Paradoxically, despite the weight gain and expansion of adipose tissue, mice presented improved glucose disposal and insulin sensitivity. The analysis of energy expenditure showed that previously infected animals displayed a better carbohydrate metabolism. Such metabolic imprinting towards the usage of carbohydrate was microbiota-dependent and conferred to the host resistance to malnutrition. 16S analysis of microbiota composition revealed an increase of Proteobacteria, in particular Suterella wadworthensis (SW) that was sustained after clearance of infection. Notably, the gavage of Suterella in juvenile or germ-free mice improved the glucose metabolism and increased glucose-dependent insulinotropic peptide (GIP) secretion. Together, this study proposes that changes in the microbiota induced by a single acute infection can provide a metabolic advantage for the host, a response that may sustain survival in part of the world in which both infectious burden and malnutrition are prevalent (AU)

• FAPESP's process: 17/02298-8 - Analysis of lipid metabolism after immunological scar induced by acute gastrointestinal infection
• Grantee: Mirian Krystel de Siqueira
• Support Opportunities: Scholarships in Brazil - Master