Research Projects

Rationale: Antimicrobial resistance (AMR) is a major public health challenge, with the human gut microbiome as a key reservoir for AMR genes. These genes can transfer resistance to pathogens, causing infections with adverse outcomes. While the microbiome prevents pathogen colonization, dysbiosis caused by antibiotics, diet, or lifestyle factors, coupled with AMR reservoirs, exacerbates health risks. This issue is critical in India, where AMR burden is high due to antibiotic misuse and environmental contamination. Poor maternal health and reduced breastfeeding further worsen infant microbiome dysbiosis, increasing the resistome. Open questions: 1. India is a hotspot for AMR, but baseline AMR reservoirs across age groups, health statuses, and antibiotic exposure remain understudied. 2. The dynamics of AMR reservoirs over time and under influences like antibiotics, infections, and microbiota-targeted interventions are poorly understood. 3. Current AMR detection methods, such as culturing and metagenomics, are costly, low-throughput, and lack resolution. 4. Microbiota engineering approaches like fecal microbiota transplants (FMT), probiotics, and breastfeeding show potential to modulate resistome, but their long-term durability and dynamics remain unexplored. Hypotheses: 1. Indian gut AMR reservoirs are enriched across the lifespan compared to healthy Western populations. 2. AMR reservoirs are modifiable through probiotics, dietary changes, and FMT, beneficially altering the resistome. Objectives: 1. Establish a baseline for gut AMR reservoirs in the Indian population across the lifespan, accounting for antibiotic exposure and demographics. 2. Develop and validate AMRGuard, a computational approach to identify AMR genes from low-depth sequencing for cost-effective profiling. 3. Assess the dynamics of gut AMR reservoirs over time and their response to microbiota-targeted interventions like FMT, probiotics, and breastfeeding. Experiments and Data: Publicly available (more than MT)500 shotgun sequenced gut metagenomics samples (India, Europe, US, East Asia), MT100 repeated culturing for AMR detection, MT250 cultured isolates. Collaborative study with Strand Life Sciences on MT250 Indian samples (MT500 metagenomics for gut, vagina, and skin sites) across lifespan, with or without antibiotic exposure, early demographics. 1. Baseline Characterization: Analyze stool samples from diverse populations to validate AMRGuard and establish AMR baselines. 2. Dynamic Analysis: Monitor resistome changes longitudinally. 3. Interventional Studies: Assess publicly available trials of FMT, probiotics, and prebiotics for altering the resistome and analyze breastfeeding's protective effects on infants. Significance: 1. Inform actionable public health policies and clinical guidelines for AMR mitigation. 2. Develop scalable, low-cost methodologies for global resistome profiling 3. Advance strategies for using probiotics, prebiotics, and FMT in AMR management.