Work done in the lab of Dr. Vineet K. Sharma at MetaBioSys group, Indian Institute of Science Education and Research Bhopal
About author
Vishnu Prasoodanan PK obtained his Bachelor’s and Master’s degree (BS-MS dual degree) in Biological Sciences from the Indian Institute of Science Education and Research Bhopal. He has done his MS Thesis project at the MetaBioSys group, department of Biological Sciences, IISER-Bhopal. His initial project in association with the MetaBioSys group was entitled ‘Reconstruction of bacterial and viral genomes from a Metagenomic mix of reads’ that evaluates a new strategy for the complete genome assembly of un-culturable bacteria using complex metagenomic data. Later on, he joined the same group to pursue doctoral studies. Initially, he was involved in the curation and analysis of metagenomic data from different environmental samples river, ocean, soil, human gut, etc. However, gradually he shifted his focus on the in-depth analysis of the gut microbiome and how different covariates like dietary patterns, lifestyle, and health status affect its compositions. He also creates scientific illustrations using digital art to explain different concepts and outcomes of scientific studies.
Dr. Sharma has been an Associate Professor at the Indian Institute of Science Education and Research Bhopal since July 2011. Dr. Sharma had obtained his Ph.D. in Bioinformatics and Biomedical Sciences from IGIB, New Delhi, in 2006. After completing his doctoral research, he worked as a Postdoctoral Researcher for two years and a Scientist at RIKEN, Japan, for the next three years. He joined IISER Bhopal after returning to India. At IISER Bhopal, Dr. Sharma has also founded the Innovation and Incubation Centre of Entrepreneurship (IICE). The main focus of Dr. Sharma’s lab is to gain functional insights into the healthy human microbiome in Indian and other populations and also to compare it with the selected disease microbiomes. For the first time, Dr. Sharma’s group has sequenced significant bird, animal, and plant genomes, including Peacock, Indian Tiger, Turmeric, Giloy, Aloe vera, Banyan tree, Peepal tree, and carried out the most extensive gut microbiome and scalp microbiome study in the Indian population. His group also employs machine learning and artificial intelligence approaches to carry out large-scale human gut data analysis and develop new algorithms and software using the BIG data of Biology.
Interview
How would you explain your research outcomes to the non-scientific community?
India is a country of diversities, which can be found in the culture, traditions, language, and even in the dietary habits of individuals. The variations in diet result from differences in local culture, geographical location (coastal areas, mountains, or desert), and socio-economic status. Even though Indians majorly follow a vegetarian diet, vegetables and fruits depends on the seasons. Besides, choice of meals, preparation styles, and usage of spices are also different in each geographical region of India. These dietary patterns and lifestyles have a significant role in shaping the composition of microbes residing in the human gut (called as human gut microbiome). It was always fascinating for me to explore the composition of the gut microbiome in the Indian population. To date, most of the human gut microbiome studies were focused on western populations of the world, while non-western populations that differed significantly in diet and lifestyle remain largely understudied. Considering the extensive potential of human gut microbiome studies to get translated to biomedical applications and therapeutics, the availability of deeply sequenced microbiome cohorts from non-western populations will substantially translate the study outcomes into medicinal products and diagnostic methods. In the light of the above, marking India in the global gut microbiome landscape becomes crucial.
Being mindful of these facts, the MetaBioSys research group had conducted a pilot study on (DB Dakan et al.) gut microbiome composition in the Indian population by collecting faecal samples from individuals residing in two different regions that vary primarily in dietary patterns. This was the first extensive effort to reveal the composition of the Indian gut microbiome and compare it with the gut microbiome of other populations. Using combined approaches of 16S rRNA gene sequencing, metagenomic analysis, and metabolomic profiling of the samples, the analysis revealed the unique composition of the Indian gut microbiome. This study also identified and annotated all microbial genes present in the human gut and established the Indian gut microbial gene catalogue. Also, reported diverse functions these microbes take part in the human gut. Interestingly, Prevotella was the most abundant microbial genus in the Indian population.
As the next step, our focus slowly shifted towards “the role of Prevotella in the human gut, particularly in India.” Rigorous literature search indicated a high prevalence of P. copri in the gut microbiomes of selected non-western populations, including the local people of Madagascar, Peru, and Tanzania. On the other hand, gut microbiome studies conducted in western populations indicated enrichment of Bacteroides, Ruminococcus and showed a very low abundance of Prevotella. These intriguing observations ignited a thought that “Is there a variation in strain-level composition of Prevotella genus in populations with different dietary patterns and lifestyle? If yes, what can be the possible implication at functional level?” With this in mind, we carried out a comprehensive analysis of the composition, diversity, and functional role of Prevotella species in the global gut microbiome by including 200 healthy samples from the Indian population that primarily consumes plant-based diets. For comparative analysis, we used Prevotella-rich non-western populations (Madagascar, Tanzania, and Peru) and western populations (US, Spain, Netherlands, and Italy) that primarily consumed the animal-based diets and showed a low abundance of Prevotella. 189 Inflammatory Bowel Disease (IBD) samples were also analyzed for examining the variation in Prevotella composition based on health status. Unfortunately, no bacterial genome database was available from the Prevotella genus with a complete representation of unculturable and metagenomically reconstructed genomes, which was crucial in gaining deeper insights into the functional roles of Prevotella. This scenario necessitated the construction of a comprehensive Prevotella genome database containing 2,204 genomes/bins and a Prevotella gene catalogue containing 2.9 million genes that include the latest information on the novel cultured and metagenomically reconstructed genomes.
This study, comprising the largest cohort of previously unexplored Indian populations and its comparison with other non-western and western populations, provided new insights into the yet understudied role of Prevotella genus in the human gut. It reemphasized the uniqueness of the Indian gut microbiome with a high abundance of Prevotella genus compared to other populations. The metagenomic composition of Prevotella genomes revealed the highest inter-sample variation among Indians, attributed to the inclusion of samples from diverse geographical regions of India differing in diets and cooking styles. Even though the gut microbiome composition of the Indian population is significantly different from all other populations, it is comparatively similar to non-western populations (mainly Tanzania and Peru) than to the western populations (US, Netherlands, Spain, and Italy). In addition, the majority of Prevotella genomes in Indian and non-western populations are of P. copri. In contrast, western populations were primarily dominated by Bacteroides. The high consumption of a plant-based high-fiber diet is plausibly the primary reason for the high abundance of Prevotella in Indian and other non-western populations, in contrast to the consumption of a ‘typical western diet’ in western populations. Further exploration in this direction unveiled the potential role of P. copri microbes in metabolising complex plant polysaccharides in the gut of individuals consuming a high fibre diet. We also identified specific genomic loci (polysaccharide utilization loci, PUL) from P. copri genomes for metabolising complex plant polysaccharides. The Prevotella species in western healthy and IBD populations were diverse and enriched in known inflammatory Prevotella species like P. intermedia, P. pallens, P. oryzae, P. koreensis, and P. ihumii with high virulence and antibiotics resistance genes. In addition, these species are also reported to be a part of the oral microbiome in western populations and have been associated with oral inflammatory conditions. Perhaps, this indicates the possible mouth-to-gut transmission of inflammation associated with Prevotella species and its association with dysbiosis of the human gut microbiome during gut inflammations.
How do these findings contribute to your research area?
Recent studies reported the higher incidence and prevalence of gut inflammatory conditions in western populations associated with adoption of western lifestyle and dietary habits. In comparison, India is among the few countries with the lowest incidence of gut inflammations reported. One of the reasons for the low incidence of inflammatory gut diseases such as Inflammatory Bowel Disease (IBD), Irritable Bowel Syndrome (IBS), and colorectal cancer in the Indian population is the consumption of a high-fiber diet where the role of the gut microbiome becomes crucial in the metabolism of the complex polysaccharides present in this kind of diet. The leading players of complex plant-polysaccharides metabolism in the non-western population are Prevotella species. This study revealed the composition and functional aspects of Prevotella species in the global gut microbiome by including the largest yet diverse cohort from India. Prevotella turned out to be a highly diverse genus that exhibits compositional variations in both inter-individual and inter-population comparisons of the human gut microbiome. The members of this genus include several strains of plant-polysaccharide metabolizing P. copri and inflammation-associated species like P. intermedia, P. pallens, etc. The positive association of gut residing P. copri with glucose homeostasis and cardiometabolic markers explain the intriguingly high abundance of this species in the gut microbiome of healthy Indian and non-western population that consumes a plant-associated carbohydrate and fiber-rich ingredients as the major component in the diet. Providing insights on the unique gut microbiome composition of the Indian population emphasizes the importance of considering inter populational variations while pursuing the long-term goal of personalized medicine. Based on these aspects, the results of the study will find applications in the development of new prebiotics, probiotics, and early diagnostic methods to treat gut disorders.
“the results of the study will find applications in the development of new prebiotics, probiotics, and early diagnostic methods to treat gut disorders.”
What was the exciting moment during your research?
The most exciting moment while carrying out this analysis was when we identified the distinct clustering of Indian gut microbiome samples in comparison with the global gut microbiome based on the microbial species abundance. This result backed our hypothesis that the distinct dietary patterns in the Indian population have a significant role in modulating the Indian gut microbiome composition and its functional potential. This excitement geared up by observing the highest abundance of Prevotella in the Indian population compared to all other non-western and western populations. These two key observations ignited several questions regarding the variable composition of this unique bacterial genus in populations having different lifestyles and dietary patterns.
What do you hope to do next?
Distinct clustering of Indian gut microbiome samples in terms of whole microbial species composition and the composition of Prevotella species indicates the possible existence of several novel microbial species that can carry out diverse metabolic functions. In the future, we are planning to extract more information regarding the novel species of Prevotella and characterize them using culturomics and computational approaches.
Where do you seek scientific inspiration from?
The human body contains 39 trillion cells of microbial origin, which is more than the total human cells in our body. Moreover, the repertoire of 20 million genes of the human microbiome can take part in a diverse range of metabolic functions. These facts signify the importance of studying the human microbiome present in oral, gut, skin, lung, and vaginal sites and different covariates that influence its composition and inter-individual variation. The human gastrointestinal tract harbors approximately 100 trillion micro-organisms, and a healthy gut microbiome is essential for nutrition and host digestion. Dysbiosis in the gut microbiome composition has significant phenotypic implications, including disease conditions. In India, human microbiome research is in its primitive stage, and it is crucial to elucidate how different covariates affect human microbiome composition. This will lead to huge and meaningful contributions in the biomedical translation of study outcomes from the largely understudied Indian population. Closely watching our dietary patterns and small-level implications in physiology also ignites the interest to study this topic. Scientific discussions with our colleagues and keen observation of the world around us with proper tracking of the studies in this field inspire us to pursue more.
How do you intend to help Indian science improve?
A considerable advancement in human microbiome studies happened in the last two decades. The majority of these studies comprise large sets of deeply phenotyped cohorts from the western population for a comprehensive analysis of human microbiome composition and its biomedical translation. However, India is falling behind in collecting large cohort datasets to explore distinctness and diversity in microbiome composition. We need to conduct more large-scale studies with cutting-edge research infrastructure to mark our contribution to the scientific world.
Reference
Prasoodanan P. K., V., Sharma, A.K., Mahajan, S. et al. Western and non-western gut microbiomes reveal new roles of Prevotella in carbohydrate metabolism and mouth–gut axis. npj Biofilms Microbiomes 7, 77 (2021). https://doi.org/10.1038/s41522-021-00248-x
Edited by: Manveen K Sethi