TY - JOUR
T1 - Patients infected with Mycobacterium africanum versus Mycobacterium tuberculosis possess distinct intestinal microbiota
AU - Namasivayam, Sivaranjani
AU - Diarra, Bassirou
AU - Diabate, Seydou
AU - Sarro, Yeya Dit Sadio
AU - Kone, Amadou
AU - Kone, Bourahima
AU - Tolofoudie, Mohamed
AU - Baya, Bocar
AU - Diakite, Mahamane T.
AU - Kodio, Ousmane
AU - Cohen, Keira
AU - Holl, Jane
AU - Achenbach, Chad J.
AU - Chatterjee, Soumya
AU - Murphy, Robert Leo
AU - Bishai, William
AU - Diallo, Souleymane
AU - Sher, Alan
AU - Maiga, Mamoudou
N1 - Publisher Copyright:
© 2020, Public Library of Science. All rights reserved.
PY - 2020/5
Y1 - 2020/5
N2 - 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 coendemic infections either as biomarkers or as a contributing determinant.
AB - 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 coendemic infections either as biomarkers or as a contributing determinant.
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U2 - 10.1371/journal.pntd.0008230
DO - 10.1371/journal.pntd.0008230
M3 - Article
C2 - 32401750
AN - SCOPUS:85084626324
SN - 1935-2727
VL - 14
SP - 1
EP - 20
JO - PLoS neglected tropical diseases
JF - PLoS neglected tropical diseases
IS - 5
M1 - e0008230
ER -