Abstract
A mutual interplay exists between adaptive immune system and gut microbiota. Altered gut microbial ecosystems are associated with the metabolic syndrome, occurring in most obese individuals. However, it is unknown why 10–25% of obese individuals are metabolically healthy, while normal weight individuals can develop inflammation and atherosclerosis. We modeled these specific metabolic conditions in mice fed with a chow diet, an obesogenic but not inflammatory diet—mimicking healthy obesity, or Paigen diet—mimicking inflammation in the lean subjects. We analyzed a range of markers and cytokines in the aorta, heart, abdominal fat, liver and spleen, and metagenomics analyses were performed on stool samples. T lymphocytes infiltration was found in the aorta and in the liver upon both diets, however a significant increase in CD4+ and CD8+ cells was found only in the heart of Paigen-fed animals, paralleled by increased expression of IL-1, IL-4, IL-6, IL-17, and IFN-γ. Bacteroidia, Deltaproteobacteria, and Verrucomicrobia dominated in mice fed Paigen diet, while Gammaproteobacteria, Delataproteobacteria, and Erysipelotrichia were more abundant in obese mice. Mice reproducing human metabolic exceptions displayed gut microbiota phylogenetically distinct from normal diet-fed mice, and correlated with specific adaptive immune responses. Diet composition thus has a pervasive role in co-regulating adaptive immunity and the diversity of microbiota.
Highlights
The main feature of obesity is an excess of adipose tissue, which is the result of an imbalance existing between the intake and the expenditure of energy
Our analyses showed a great enrichment in myeloid cells, CD45+, CD11b+, CD11c, F480+, Ly6G+ upon Paigen diet (PD)- in the spleen compared to ND- and high fat diet (HD)-feeding (Figure 4A), a massive lymphocyte infiltration in the aorta and in the liver upon both PD and HD compared to ND diet (Figure 4B), a significant increase in CD4+ and CD8+ positive cells percentage exclusively in the aorta and in the hearts of PD-fed animals compared to ND and HD (Figure 4C); no changes were observed in abdominal fat tissues
Individuals with adverse metabolic status despite a normal body mass index (BMI) have been described (MSL = metabolic syndrome lean; Karelis, 2008; Flegal et al, 2013). It is currently unclear whether metabolic dysfunctions affects the higher morbidity and mortality observed in individuals with higher BMI: the concept of “benign obesity” has been challenged by some meta-analyses (Kramer et al, 2013) but not by others (Dhana et al, 2016), suggesting that MetS and not elevated BMI is an unequivocal risk factor for cardiovascular diseases (CVD)
Summary
The main feature of obesity is an excess of adipose tissue, which is the result of an imbalance existing between the intake and the expenditure of energy. Under healthy conditions commensal bacteria colonizing the gut interplay with the host immunity to maintain a state of homeostasis In this respect, an immune system–gut microbiota cooperation which operates at optimal levels is instrumental for setting protective mechanisms against pathogenic agents and, at the same time, for keeping in check the regulatory pathways implicated in the avoidance of triggering immune responses to harmless antigens (Belkaid and Hand, 2014). An immune system–gut microbiota cooperation which operates at optimal levels is instrumental for setting protective mechanisms against pathogenic agents and, at the same time, for keeping in check the regulatory pathways implicated in the avoidance of triggering immune responses to harmless antigens (Belkaid and Hand, 2014) This reciprocal interaction involves both innate (Thaiss et al, 2014) and adaptive immunity (Kato et al, 2014; Zhang and Luo, 2015). It has been suggested that dysbiosis can cause immune dysfunctions by activating B and T cells regardless of their distance from the location of their induction (Honda and Littman, 2016), there is scarce knowledge on the relationship between distinct immune cell populations, more in particular those belonging to the adaptive immunity, and the heterogeneity of digestive system-residing and symbiotic bacteria
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