We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Patients infected with Mycobacterium africanum versus Mycobacterium tuberculosis possess distinct intestinal microbiota.
- Authors
Namasivayam, Sivaranjani; Diarra, Bassirou; Diabate, Seydou; Sarro, Yeya dit Sadio; Kone, Amadou; Kone, Bourahima; Tolofoudie, Mohamed; Baya, Bocar; Diakite, Mahamane T.; Kodio, Ousmane; Cohen, Keira; Holl, Jane; Achenbach, Chad J.; Chatterjee, Soumya; Murphy, Robert Leo; Bishai, William; Diallo, Souleymane; Sher, Alan; Maiga, Mamoudou
- Abstract
Background: Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB), is composed of eight subspecies. TB in West Africa, in contrast to other geographical regions, is caused by Mycobacterium africanum (MAF) in addition to M. tuberculosis (MTB), with both infections presenting similar symptoms. Nevertheless, MAF is considered to be hypovirulent in comparison with MTB and less likely to progress to active disease. In this study, we asked whether MAF and MTB infected patients possess distinct intestinal microbiomes and characterized how these microbiota communities are affected by anti-tuberculosis therapy (ATT). Additionally, we assessed if the changes in microbiota composition following infection correlate with pathogen induced alterations in host blood-gene expression. Methods: A longitudinal, clinical study of MAF infected, MTB infected patients assessed at diagnosis and two months after start of ATT, and healthy, endemic controls was conducted to compare compositions of the fecal microbiome as determined by 16S rRNA sequencing. A blood transcriptome analysis was also performed on a subset of subjects in each group by microarray and the results cross-compared with the same individual's microbiota composition. Findings: MAF participants have distinct microbiomes compared with MTB patients, displaying decreased diversity and increases in Enterobacteriaceae with respect to healthy participants not observed in the latter patient group. Interestingly, this observed elevation in Enterobacteriaceae positively correlated with enhanced inflammatory gene expression in peripheral blood and was reversed after initiation of ATT. Interpretation: Our findings indicate that MAF and MTB have distinct associations with the gut microbiome that may be reflective of the differential susceptibility of West Africans to these two co-endemic infections either as biomarkers or as a contributing determinant. Author summary: Mycobacterium africanum (MAF) is a hypovirulent mycobacterium species that is co-endemic with Mycobacterium tuberculosis (MTB) in West Africa and is selectively responsible for up to half the tuberculosis cases in this region. Why some individuals become infected with MAF versus MTB is unclear but has been suggested to be determined by differential host immune competency. Since the microbiome has now been implicated in numerous studies to generally influence host resistance to disease, we investigated whether differences in the intestinal microbiota might associate with MAF as compared with MTB infection. This report presents the first analysis of the intestinal microbiome of MAF-infected subjects as well as a comparison with the microbiota of co-endemic MTB patients and reveals that the microbiota of individuals with MAF infection display both decreased diversity and distinct differences in microbial taxa when compared to both MTB-infected and healthy controls. Furthermore, our data reveal for the first time in TB patients a correlation between the abundance of certain taxa and host blood transcriptional changes related to immune function. Our study also establishes that antibiotic treatment induces parallel changes in the gut microbiota of MAF- and MTB-infected patients. Although not directly addressed in the present study, the findings presented here raise the possibility that the microbiota or other host physiologic or immune factors closely associated with it may be a factor underlying the differential susceptibility of West Africans to MAF infection. In addition, the data identify certain commensal taxa that could be tested in future studies as specific determinants of this association.
- Subjects
WEST Africa; MYCOBACTERIUM tuberculosis; GUT microbiome; MYCOBACTERIUM; NATURAL immunity; MYCOBACTERIUM avium paratuberculosis; BLOOD testing; BURULI ulcer
- Publication
PLoS Neglected Tropical Diseases, 2020, Vol 14, Issue 5, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0008230