Background:The current research was conducted with an aim to evaluate the association of oral microbiome with potentially malignant disorders(PMDs) because tobacco usage in any form can cause dysbiosis by altering the normal microbiome. Thus, our definitive knowledge of the oral commensal bacteria can definitely be used as a potential adjunct to early diagnosis and management of PMDs. Aim:To assess the microbiological pattern in tobacco pouch keratosis lesions among migrant construction workers in Chennai. Objectives:1.To evaluate the medicinal potential of Bromelain against tobacco pouch keratotic lesions 2.To examine the potency of plant extract by determining MIC (Minimum Inhibitory Concentration) Methods:Here, we used standard microbiological techniques to analyze the microbiota from labial and buccal mucosa of 70 smokeless tobacco users to assess microbial composition and effects of smokeless tobacco. In vitro experimental study was carried out to evaluate the antimicrobial effects of bromelain against MDR microbes.80% methanolic extraction was employed.MIC were measured using micro dilution as per CLSI protocols. Results:The distribution of microbial isolates from smokers is shown in Table 1. Streptococcus mutans was the most prevalent bacterial isolate followed by Candida species among smokers. The potency of plant extract was examined by determining MIC.MDR isolates including C.albicans and S.mutans were significantly inhibited by plant extract. Test extracts showed promising antibacterial potential against S.mutans with low MIC values ranging between 0.019mg/ml and 10mg/ml. Conclusion:The ecological shift to dysbiosis is a significant finding in oral carcinogenesis.The Bromelain extract has shown appreciable antimicrobial activities against MDR pathogens. Further investigation on a larger group of altered microbiomes can help in appropriate treatment and better prognosis by establishing relationship of altered microbiome.