Intestinal Permeability, Gut Inflammation, and Gut Immune System Response Are Linked to Aging-Related Changes in Gut Microbiota Composition: A Study in Female Mice

Author:

Gámez-Macías Paola Elizabeth12ORCID,Félix-Soriano Elisa12,Samblas Mirian2,Sáinz Neira2,Moreno-Aliaga María Jesús34,González-Muniesa Pedro34

Affiliation:

1. Faculty of Pharmacy and Nutrition, Department of Nutrition, Food Science, and Physiology, University of Navarra , Pamplona , Spain

2. Center for Nutrition Research, University of Navarra , Pamplona , Spain

3. Faculty of Pharmacy and Nutrition, Department of Nutrition, Food Science, and Physiology, and Center for Nutrition Research, University of Navarra/Navarra Institute for Health Research (IdiSNA) , Pamplona , Spain

4. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III , Madrid , Spain

Abstract

Abstract Aging entails changes at the cellular level that increase the risk of various pathologies. An association between gut microbiota and age-related diseases has also been attributed. This study aims to analyze changes in fecal microbiota composition and their association with genes related to immune response, gut inflammation, and intestinal barrier impairment. Fecal samples of female mice at different ages (2 months, 6 months, 12 months, and 18 months) and gene expression in colon tissue were analyzed. Results showed that the older mice group had a more diverse microbiota than the younger group. Additionally, the abundance of Cyanobacteria, Proteobacteria, Flavobacteriaceae, Bacteroides, Parabacteroides, Prevotellaceae_UCG-001, Akkermansia, and Parabacteroides goldsteinii increased with age. In contrast, there was a notable decline in Clostridiaceae, Lactobacillaceae, Monoglobaceae, Ligilactobacillus, Limosilactobacillus, Mucispirillum, and Bacteroides faecichinchillae. These bacteria imbalances were positively correlated with increased inflammation markers in the colon, including Tnf-α, Ccl2, and Ccl12, and negatively with the expression of tight junction genes (Jam2, Tjp1, and Tjp2), as well as immune response genes (Cd4, Cd72, Tlr7, Tlr12, and Lbp). In conclusion, high levels of diversity did not result in improved health in older mice; however, the imbalance in bacteria abundance that occurs with aging might contribute to immune senescence, inflammation, and leaky gut disease.

Funder

MINECO/FEDER of the Government of Spain

CIBER Physiopathology of Obesity and Nutrition (CIBEROBN) of Carlos III Health Research Institute

Department of University, Innovation and Digital Transformation, Government of Navarra

Publisher

Oxford University Press (OUP)

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