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.
