Malnutrition leads to increased inflammation and expression of tuberculosis risk signatures in recently exposed household contacts of pulmonary tuberculosis

Abstract

BackgroundMost individuals exposed to Mycobacterium tuberculosis (Mtb) develop latent tuberculosis infection (LTBI) and remain at risk for progressing to active tuberculosis disease (TB). Malnutrition is an important risk factor driving progression from LTBI to TB. However, the performance of blood-based TB risk signatures in malnourished individuals with LTBI remains unexplored. The aim of this study was to determine if malnourished and control individuals had differences in gene expression, immune pathways and TB risk signatures.MethodsWe utilized data from 50 tuberculin skin test positive household contacts of persons with TB - 18 malnourished participants (body mass index [BMI] < 18.5 kg/m2) and 32 controls (individuals with BMI ≥ 18.5 kg/m2). Whole blood RNA-sequencing was conducted to identify differentially expressed genes (DEGs). Ingenuity Pathway Analysis was applied to the DEGs to identify top canonical pathways and gene regulators. Gene enrichment methods were then employed to score the performance of published gene signatures associated with progression from LTBI to TB.ResultsMalnourished individuals had increased activation of inflammatory pathways, including pathways involved in neutrophil activation, T-cell activation and proinflammatory IL-1 and IL-6 cytokine signaling. Consistent with known association of inflammatory pathway activation with progression to TB disease, we found significantly increased expression of the RISK4 (area under the curve [AUC] = 0.734) and PREDICT29 (AUC = 0.736) progression signatures in malnourished individuals.ConclusionMalnourished individuals display a peripheral immune response profile reflective of increased inflammation and a concomitant increased expression of risk signatures predicting progression to TB. With validation in prospective clinical cohorts, TB risk biomarkers have the potential to identify malnourished LTBI for targeted therapy.

Integrative analysis of multimodal patient data identifies personalized predictors of tuberculosis treatment prognosis

“…TB is typically more prevalent in the undernourished population. 40 , 41 Our findings are thus consistent with these reports.…”

Nutritional Status and Associated Factors Among Adult Patients With Tuberculosis

“…Awareness of nutrition, balanced diet and regular physical activity should be improved by counselling and communication. "The authors declare no conflict of interest regarding this article" "The authors declare that all the procedures and experiments of this study respect the ethical standards in the Helsinki Declaration of 1975, as revised in 2008 (5), as well as the national law. Informed consent was obtained from all the patients included in the study".…”

“…Nutritional status is one of the most important determinants of resistance to infection, including TB. The interaction between TB and malnutrition has been well-established in the literature [3][4][5][6] . Undernutrition causes approximately 1/4 of all new TB cases worldwide and TB is one of the most frequent underlying causes of wasting 7 .…”

Prognostic Nutritional Index (PNI) in patients with severe encephalitis as a useful prognostic indicator:a multivariate analysis

“…Researchers have found that malnutrition plays an important role in the prognosis of many diseases, including infectious diseases, in ammation, and cancers. A lack of nutrition increased the susceptibility to infection, as well as reducing the quality and durability of vaccine responses 2 . An Indian study about nutritional status and pulmonary tuberculosis shown 85% patients with undernutrition had increased risk of death 3 .…”