Leprosy is back: An investigation on the role of skin microbes

Author: Nitin Bayal
National Centre for Cell Science, Pune
My presumptions about leprosy were incorrect! Books and documentaries have spoken plenty in silence but still incomplete. 
In the middle ages, it was one of the most feared diseases and was once considered as “Living Death”. There was a time when prevailing religious concepts kept our attention away from finding the root cause of leprosy transmission and religious institutions influenced the health and disease affairs. Illness due to leprosy was accepted as a curse from God or bad luck, just as many different phenomena that were not linked to cause-and-effect theory credited to the act of god, forcing people to plead and compensate for this unexplained experience. 
Although after new advances in science and technology came into existence, it became difficult to arguably justify scientific reasoning with superstitions. The dreadful infections in leprosy have much more to say than eradication objectives. Prior to perusing a Ph.D. at National Centre for Cell Science, Pune; I knew very little about leprosy and Mycobacterium leprae, the causative organism of leprosy. Leprosy which causes poor wound healing, nerve damage and if left untreated it results in permanent disfigurement or loss of body parts, has for long been associated with a social stigma. 
In India, for ages, ayurvedic preparations known as chaulmoogra oil was used to treat leprosy, and with the introduction of western medicine prescription drugs like Dapsone and Rifampicin, the catalog of every possible physical and chemical agent to indiscriminately kill the bad microbes is ever-expanding. 
It is known to us that a leprosy patient loses the ability to feel the temperature change and pain in the affected area on their body; with the current understanding on the subject, we discovered some mysterious insights on leprosy research that encouraged skin microbiome research in leprosy. We added a brief note on each idea discussed in our research group. I tried to understand the diseased states, current therapeutics, and the problems that challenge scientists in this field. 
M. leprae slowly gets resistant to new drugs and hence, raises concerns for a more severe form of the disease. In 1982, World Health Organization (WHO) released Multi-Drug Therapy (MDT) guidelines that dictate the planning and execution to eradicate leprosy. There is also the addition of newer drugs into the arsenal along with MDT treatment. Recently, scientists and clinicians speculated India accounts for 66% of leprosy patients worldwide. To challenge leprosy, WHO accelerated a global leprosy strategy for 2016-2020. A team of scientists led by Dr. GP. Talwar at All India Institute of Medical Science (AIIMS); New Delhi developed a vaccine in the 1970s that is finally recommended to launch on 2nd October 2019 after 36 years of testing in the clinical trials. As of now, it is well recognized that leprosy elimination has never been achieved actually in India. 
Moreover, the frequency of resistant mutants also varies to different drugs, MDT treatment also kills the bacteria that are naturally resistant to drugs on the affected sites. It also affects the normal skin bacterial community. 
Skin is the primarily affected organ in leprosy. This is where the skin microbiome plays its role to support normal homeostasis. The microbiome consists of an ecosystem of billions or trillions of microorganisms living in and on our bodies including skin. There is growing evidence that skin infections and drug abuse change or disturbs the skin microbiota in various types of skin pathological conditions like acne, eczema, psoriasis, skin allergies, and wounds. 
We knew that both research scientists and clinicians play a critical role in the successful completion of studies on human subjects through mutual collaborations. While communicating with scientists, dermatologists, and workers of all levels at different NGOs, we finally found our collaborations in 2015 with leprosy clinics at LEPRA and TLM organizations for clinical samples. Then it was followed by regular meetings with patients and leprologists at leprosarium, where patients are kept for their treatment. The situation of patients was horrible because of their constant suffering, thus to understand the relationship between the skin microbiome and M leprae infection, researchers at DBT-National Centre for Cell Science and Bio-Sciences R&D, TCS Innovation Labs, Pune also collaborated to conduct a new study on the skin microbial communities from lesional and non-lesional skin of Indian leprosy patients undergoing multi-drug regimen treatment and healthy individuals covering two different geographical locations viz. Hyderabad and Miraj in India. 
We obtained ethical and biosafety clearances and collaborated with Dr. Vijayalakshmi Valluri at LEPRA, Hyderabad and, Dr. Rohini Suryavanshi at TLM, Miraj, Maharashtra for clinical samples. We collected skin samples and extracted microbial DNA. We have used DNA sequencing methodologies and analysis tools to define the cutaneous microbiota. Our study has shown that the skin microbiota of healthy persons and leprosy patients have significant differences in its variety and abundance. The reasons also include the role of various external and internal factors comprising skin pH, skin thickness, skin moisture, hygiene, climate, etc. The photograph shown above was taken with consent at Richardson leprosy hospital, Miraj, Maharashtra, and pixelated to maintain the confidentiality of the leprosy patient.
Together with Dr. Milind S. Patole as doctoral co-supervisor, Dr. Dhiraj Paul, and Mr. Sunil Nagpal, one of my colleagues at TCS Innovation Labs, we have completed computational analysis on high-throughput sequencing data. We have published the first report on the structure of skin microbiota from India in Springer Nature journals i.e., Nature Scientific Data and Nature Scientific Reports journals. The corresponding authors, Dr. Shekhar C. Mande is Secretary DSIR and Director General, CSIR, New Delhi and Dr. Sharmila S. Mande is Chief Scientist and Head of Bio-Sciences R&D, TCS Research, Pune. They are leading scientists and specialized in Structural Biology and Microbiome research respectively.
Our analysis shows differences in the microbiota of affected and unaffected sites on the skin of leprosy patients and similarities among healthy persons irrespective of our sampling sites in India. Microbial diversity probes a distinct depletion of Staphylococcus genera in samples from affected sites of leprosy patients. Major abundant bacteria observed were Pseudomonas, Staphylococcus, Paracoccus, Brevundimonas, Limnobacter, Methylobacterium, Propionibacterium, Corynebacterium, Kocuria, and Streptococcus on the leprosy patient’s skin. It also shows a significant decline in firmicutes-related bacteria in leprosy patients in comparison to healthy individuals. It was a strange coincidence when M leprae attacks and occupy spaces in human bodies by either high exposure to infections or low immunity or both situations. M leprae is very intelligent, being a metabolically challenged bacterium it has managed to survive harsh conditions and still a mystery for the researchers for its cultivation in laboratory conditions. We are also afraid of liberal use of antibiotics and antiseptics that not only results in the extinction of some good bacteria but also kept the fortunate ones under constant threat. 
The aspect of working with microbiome research can help skin microbiome transplantation science that corresponds to better disease management and diagnosis. A healthy microbiome protects humans from harmful settlers and infections by pathogens or opportunistic microorganisms. 
Nowadays, many ventures are introducing probiotic products in the skin healthcare system and focusing on implications of skin’s health and appearance. The future of treating skin diseases is hopeful from microbiome research. However, despite these positive developments, measures to improve the healthcare system are also required. Humans often err in their haste. After all the great riches of leprosy are its paradoxes. If we are losing this time that will be another paradox, our luck may also prove contrary.​

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Author Bio: Nitin is a microbiome researcher at DBT-National Institute of Immunology, New Delhi. His interest mainly focus on data analytics in healthcare sector. He is an acclaimed scientific illustrator with a well disposed eye for art in daily lives. Nitin holds a degree of Master of Science in Molecular and Human Genetics and published his Ph.D work on leprosy research. His work is guided by a need to rationalize, make things beautiful, combine science with art and connect ideas.
Area of research: Skin biology, microbiome, sequencing technologies
Google Scholar link: https://scholar.google.com/citations?user=79o59fkAAAAJ&hl=en
Twitter handle: @BayalNitin