Abstract
The administration of a high fat content diet is an accelerating factor for metabolic syndrome, impaired glucose tolerance, and early type 2 diabetes. The present study aims to assess the impact of a high fat diet on tuberculosis progression and microbiota composition in an experimental animal model using a C3HeB/FeJ mouse strain submitted to single or multiple consecutive aerosol infections. These models allowed us to study the protection induced by Bacillus Calmette-Guérin vaccination as well as by the natural immunity induced by chemotherapy after a low dose Mycobacterium tuberculosis infection. Our results show that a high fat diet is able to trigger a pro-inflammatory response, which results in a faster progression toward active tuberculosis and an impaired protective effect of BCG vaccination, which is not the case for natural immunity. This may be related to dysbiosis and a reduction in the Firmicutes/Bacteroidetes ratio in the gut microbiota caused by a decrease in the abundance of the Porphyromonadaceae family and, in particular, the Barnesiella genus. It should also be noted that a high fat diet is also related to an increase in the genera Alistipes, Parasuterella, Mucispirillum, and Akkermansia, which have previously been related to dysbiotic processes. As diabetes mellitus type 2 is a risk factor for developing tuberculosis, these findings may prove useful in the search for new prophylactic strategies for this population subset.
Highlights
Tuberculosis (TB) is still a major challenge facing humanity in the twenty-first century
Two different experiments were planned in order to evaluate: (a) the effect of high fat diet (HFD)-induced obesity on the mouse model of active TB using the C3HeB/FeJ strain, as well as Bacillus Calmette-Guérin (BCG) vaccination and two different types of challenge [single infection or multiple consecutive infections (SI or Multiple consecutive infections (MCI))]; and (b) the effect of BCG vaccination compared to natural immunity (NI) in the same comorbidity model
Before Mycobacterium tuberculosis (Mtb) challenge there was a clear difference in the slope of the body weight increase between normal diet (ND) and HFD (Figures 1A–F; Table S1; Figure S1)
Summary
Tuberculosis (TB) is still a major challenge facing humanity in the twenty-first century. In several infectious diseases, such as communityacquired pneumonia, sepsis, Chagas disease, or TB, there are consistent epidemiological data showing the advantages of obesity, with negative outcomes being inversely related to BMI. This benefit can be seen for a variety of surgical and nonsurgical conditions [6, 7]. Metabolic syndrome intensifies with an increase in adiposity, thereby raising the level of immune protection, which at the same time is counterbalanced by the deleterious effects of dysglycemia. This process is known as the “obesity paradox” [6]
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