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Elucidating The Role Of Lactobacillus Rhamnosus Gg In The Prevention Of Mycobacterium Tuberculosis Infection

Posted on:2017-04-23Degree:MasterType:Thesis
Country:ChinaCandidate:ChiwalaFull Text:PDF
GTID:2334330488970483Subject:Biochemistry and Molecular Biology
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Mycobacterium tuberculosis,the causative agent of TB affects the bodily organs non-selectively and is a leading cause of death from infectious agent worldwide.While there is a reduction in mortality from TB following the inception of Millennium Development Goals,it has constantly remained at pandemic levels.To achieve the END TB goal by 2035,there is need to focus on the host not just the pathogen for Mycobacterium tuberculosis has been evolving over the years resulting in drug resistant TB.Host directed therapeutic(HDT)agents have potential to disrupt M.tuberculosis pathogenesis,facilitate the protective immune response or reduce deleterious responses that exacerbate disease.To determine if Lactobacillus rhamnosus GG has potential to protect against development and dissemination of Mycobacterium tuberculosis,30 female SD rats were assigned to receive either L.rhamnosus 5×108-11,Placebo or nothing at all(control group).Those in the placebo and L.rhamnosus group were immunosuppressed with Prednisone 6mg/kg/bwt/day for 3 weeks and were later exposed to 107-9 Mycobacterium smegmatis via aerosol spray betvween 30 to 60minutes for 5days.Bacterial load counts,cytokine expression in either blood,lung or kidney tissues was done on days 7,10,14 and 21 post last aerosol spray.From days 42 to 45,the animals were re-exposed to M.smegmatis with the above parameters checked on day 47,50,54,57,60,63 and 70.Results were analysed by ANOVA,T-test as well as Chi-square with GraphPad prism 5 and were significant at p<0.05.Notably,L.rhamnosus treated animals cleared bacteria from the lungs faster than the placebo group(p value 0.0049)but had more bacteria in spleen throughout the study period.In addition,L.rhamnosus treated animals manifested less tissue pathology on H&E staining than placebo group.Interestingly,L.rhamnosus treated animals had low pulmonary cytokine expression 7 days post infection but expressed but they had more expression from days 10 till 21 than the placebo animals.On the other hand,serum cytokine expression was significant for slight elevation of proinflammatory cytokines in the L.rhamnosus animals on day 7 but later dropped during the course of the study.Following reinfection on day 42 to 45,L.rhamnosus treated animals had less disseminated diseases than the placebo group and had significantly enhanced expression of IL-2 and other Th1 cytokines for a greater period than the placebo or control group.It was therefore concluded that Lactobacillus rhamnosus GG offers benefits to the host in the prevention of Mycobacterium tuberculosis infection by minimising the immunopathology as well as enhance rapid clearance which could lower the duration of treatment and minimise sequelae of disease.In addition,L.rhamnosus is protective against disseminated disease possibly due to enhanced IL-2 expression following reinfection or reactivation.As such,it will be appropriate to include L.rhamnosus on the list of HDTs against Mycobacterium tuberculosis as we move towards eliminating TB by 2035.
Keywords/Search Tags:Mycobacterium tuberculosis, Mycobacterium smegmatis, Lactobacillus rhamnosus, End TB, Host Directed Therapeutics
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