Dietary patterns, microbiome, metabolome and cardiovascular disease risk in transitioning India

Lead Research Organisation: London Sch of Hygiene and Trop Medicine
Department Name: Epidemiology and Population Health

Abstract

A growing number of people living in India are suffering from heart disease. Many researchers think that this is because of changes in diet (from traditional diets rich in cereals to western diets rich in sugars, fats and meat products) that occur when countries develop economically. The dietary changes in India appear to be different from other developing countries due to a strong cultural preference for vegetarian food. Therefore, our goal is to understand how dietary changes in India may be influencing the risk of heart disease. We are particularly interested in the role of bacteria that usually live harmlessly in our gut, as new research suggests their involvement in many health conditions.

For nearly two decades, we have been conducting health-related research in 29 villages on the edge of Hyderabad city in South India. Over the past decade, these villages have undergone rapid uneven development providing a unique opportunity to understand the health effects of dietary changes. In 2010-12, we collected data on diet and heart health of ~7,000 individuals from this community. We now plan to collect similar data on these individuals, including their blood and stool samples. We will use state-of-the-art technologies to identify the patterns of small molecules in the blood (i.e. metabolomics) and bacteria in the gut (i.e. microbiome). We will then analyse the data to understand how dietary patterns and gut bacteria may influence the risk of heart disease at a deeper (molecular) level. Findings from this research will inform dietary guidelines and food policy in India, and ultimately lead to a reduction in economic loss to the country from heart disease.

Technical Summary

The prevalence of cardiovascular disease in India is increasing rapidly. This is widely attributed to changes in dietary patterns (from traditional to western) associated with economic transition, but the molecular mechanisms by which dietary patterns specific to India (i.e. predominantly vegetarian) influence the risk of cardiovascular disease are unknown.

The Andhra Pradesh Children and Parents Study is an intergenerational cohort study in 29 villages near Hyderabad city, South India. In 2010-12, detailed data on diet and cardiovascular disease risk factors were collected for ~7000 participants, and blood samples banked. The peri-urban study villages have since experienced rapid unplanned development, providing a unique opportunity for prospective investigation of mechanisms by which dietary transition may influence the risk of cardiovascular disease.

We plan to re-examine the cohort in 2020-22 to collect data on dietary patterns, cardiovascular risk factors, and key hypothesised mechanisms (i.e. gut microbiome, blood metabolome, immunome and micronutrients) to address the following objectives:

-Identify predominant patterns for diet, gut microbiome and blood metabolome in this transitional community, and any systematic variations in these by the level of village development

-Investigate the key molecular pathways hypothesised to explain the relationship between dietary patterns and cardiovascular disease risk

-Investigate the role played by the gut microbiome in the relationship between dietary patterns and cardiovascular disease risk, specifically through changes in immunological functioning and micronutrient deficiencies

Findings from this study may inform dietary guidelines and food policy in India, and ultimately lead to a reduction in economic burden from cardiovascular disease epidemic in India.

Planned Impact

The proposed research has the potential for a range of direct and indirect impacts on the Indian society.

Potential impact 1: Population diet and health
Dietary advice is often perceived by the public with scepticism due to frequent reports of contradictory findings. Indian culture in particular has a lot of myths involving diet. The issues are compounded by rapidly changing dietary patterns as a result of economic development. The cultural preference for vegetarianism makes it difficult to extrapolate dietary guidelines from other settings or for healthcare providers in India to provide dietary advice for specific health conditions. Improved understanding of mechanisms by which diet could influence cardiovascular disease and other conditions will provide a strong evidence base on which to base dietary advice for Indians. As healthy diet is a key determinant of a broad range of health conditions, both physical and mental, optimal diets are likely to have wide-ranging impact on the general health and well-being of the Indian population.

Potential impact 2: Science and technology
We will use several innovative technologies in the proposed research to characterise the metabolomics, microbiome and immunome. So far, the use of such technologies in humans has been limited to small samples in India. A large-scale project will provide Indian scientific community with experience to manage 'big data' from multiple platforms and undertake complex analyses to generate new knowledge. Such knowledge can then be applied to a range of other samples and industries (e.g. -omics of food samples). Hyderabad is a hub for biotechnology start-ups, many of which have emerged from academic centres, providing a template for others to follow.

Potential impact 3: Industry
The food industry is currently making considerable investments in understanding dietary preferences as they are under pressure from policy makers to develop food products that are tasty, but low in calories, salt and sugar. The findings of this research will be of great interest to them. The findings from the microbiome-related research will have value for the probiotic and microbiome manipulation industries.

Potential impact 4: Governmental policies
The findings from this research will inform national policies in several interrelated areas. For example, the agricultural and rural development policy may be influenced by what foods dietary guidelines encourage people to consume. This is topical as many farmers in India are changing their land use to make more animal produce, which has potential impact on green-house emissions and climate change mitigation policies.

Potential impact 5: Economic productivity and inequalities
Non-communicable diseases, including cardiovascular disease, was estimated to cost the Indian economy $6 trillion during 2012-30, owing to the loss of productivity in a relatively young workforce afflicted with cardiovascular disease. The cost of medical treatment of cardiovascular disease is known to push many low-income households in India into catastrophic poverty, further increasing social inequalities. The urban poor are one of the groups at most risk of diet-related non-communicable diseases. Improvement in diets of transitioning Indians may mitigate some of these adverse consequences of economic development in India.

Publications

10 25 50
 
Description We examined the association between meat intake and cardio-metabolic risk in two population-based studies from India. Results were highly consistent between the two studies: greater intake of meat was associated with increased risk of hypertension, diabetes and dyslipidemia. Elevated risk was observed even at relatively low absolute levels of meat intake (e.g. 15-20g of meat per day). Results were robust to adjustment for confounding factors such as age, sex, educational status, tobacco use, alcohol use, physical activity, total energy intake and fruit and vegetable intake. This provides further indication of higher susceptibility to the cardio-metabolic effects of meat intake among Indians; we are seeking further funding to confirm and explain this observation.
Exploitation Route We are preparing three manuscripts for publication in open-access journals on the cardio-metabolic effects of meat intake in the Indian population, interaction with lean body mass, and a review of metabolomic markers for cardiovascular disease. These will be informative to both academics and policy-makers in the field of diet/meat intake in India.
Sectors Agriculture, Food and Drink,Healthcare

 
Description During our project inception and collaborator group meetings, we have continuously engaged with scientists from the National Institute of Nutrition, India, the key body providing nutritional recommendations for Indians. Our findings about harmful effects of meat intake in Indians and forthcoming publications will feed into upcoming dietary recommendations about meat intake in India (which are currently lacking).
First Year Of Impact 2019
Sector Agriculture, Food and Drink,Healthcare
Impact Types Societal

 
Description Novel collaboration of UK and Indian scientists to elucidate metabolomic pathways of dietary risks in Indians 
Organisation Aberystwyth University
Country United Kingdom 
Sector Academic/University 
PI Contribution As PI of the grant, I initiated the collaboration and brought all of the teams on board. My team coordinated a 2-day collaboration meeting in Hyderabad (Novemeber 2019), where we developed a plan for a program of research aiming to elucidate metabolomic pathways between diet and cardiovascular risk in Indians. I led on the coordination and writing of the grant proposal which arose from the meeting.
Collaborator Contribution All collaborators contributed subject-specific knowledge and expertise towards conceptualizing and writing the grant proposal. Collaborators from National Institute of Nutrition and Yenepoya University collected samples and conducted pilot metabolomic analyses to inform development of the proposal. Collaborators from Public Health Foundation of India and London School of Hygiene and Tropical Medicine conducted epidemiological analyses of existing data and presented findings at the meeting.
Impact Three manuscripts are under preparation relating to pilot work and discussions from the collaboration meeting. Scientific advisers to the Government of India (collaborators from National Institute of Nutrition) were present at the meetings and instrumental in the design and framing of the grant proposal. Building on discussions and pilot work presented at the collaboration meeting, a grant proposal funding application has been submitted (currently pending funding decision).
Start Year 2019
 
Description Novel collaboration of UK and Indian scientists to elucidate metabolomic pathways of dietary risks in Indians 
Organisation CSIR - Institute of Microbial Technology
Country India 
Sector Public 
PI Contribution As PI of the grant, I initiated the collaboration and brought all of the teams on board. My team coordinated a 2-day collaboration meeting in Hyderabad (Novemeber 2019), where we developed a plan for a program of research aiming to elucidate metabolomic pathways between diet and cardiovascular risk in Indians. I led on the coordination and writing of the grant proposal which arose from the meeting.
Collaborator Contribution All collaborators contributed subject-specific knowledge and expertise towards conceptualizing and writing the grant proposal. Collaborators from National Institute of Nutrition and Yenepoya University collected samples and conducted pilot metabolomic analyses to inform development of the proposal. Collaborators from Public Health Foundation of India and London School of Hygiene and Tropical Medicine conducted epidemiological analyses of existing data and presented findings at the meeting.
Impact Three manuscripts are under preparation relating to pilot work and discussions from the collaboration meeting. Scientific advisers to the Government of India (collaborators from National Institute of Nutrition) were present at the meetings and instrumental in the design and framing of the grant proposal. Building on discussions and pilot work presented at the collaboration meeting, a grant proposal funding application has been submitted (currently pending funding decision).
Start Year 2019
 
Description Novel collaboration of UK and Indian scientists to elucidate metabolomic pathways of dietary risks in Indians 
Organisation Indian Council of Medical Research (ICMR)
Country India 
Sector Public 
PI Contribution As PI of the grant, I initiated the collaboration and brought all of the teams on board. My team coordinated a 2-day collaboration meeting in Hyderabad (Novemeber 2019), where we developed a plan for a program of research aiming to elucidate metabolomic pathways between diet and cardiovascular risk in Indians. I led on the coordination and writing of the grant proposal which arose from the meeting.
Collaborator Contribution All collaborators contributed subject-specific knowledge and expertise towards conceptualizing and writing the grant proposal. Collaborators from National Institute of Nutrition and Yenepoya University collected samples and conducted pilot metabolomic analyses to inform development of the proposal. Collaborators from Public Health Foundation of India and London School of Hygiene and Tropical Medicine conducted epidemiological analyses of existing data and presented findings at the meeting.
Impact Three manuscripts are under preparation relating to pilot work and discussions from the collaboration meeting. Scientific advisers to the Government of India (collaborators from National Institute of Nutrition) were present at the meetings and instrumental in the design and framing of the grant proposal. Building on discussions and pilot work presented at the collaboration meeting, a grant proposal funding application has been submitted (currently pending funding decision).
Start Year 2019
 
Description Novel collaboration of UK and Indian scientists to elucidate metabolomic pathways of dietary risks in Indians 
Organisation Public Health Foundation of India
Country India 
Sector Public 
PI Contribution As PI of the grant, I initiated the collaboration and brought all of the teams on board. My team coordinated a 2-day collaboration meeting in Hyderabad (Novemeber 2019), where we developed a plan for a program of research aiming to elucidate metabolomic pathways between diet and cardiovascular risk in Indians. I led on the coordination and writing of the grant proposal which arose from the meeting.
Collaborator Contribution All collaborators contributed subject-specific knowledge and expertise towards conceptualizing and writing the grant proposal. Collaborators from National Institute of Nutrition and Yenepoya University collected samples and conducted pilot metabolomic analyses to inform development of the proposal. Collaborators from Public Health Foundation of India and London School of Hygiene and Tropical Medicine conducted epidemiological analyses of existing data and presented findings at the meeting.
Impact Three manuscripts are under preparation relating to pilot work and discussions from the collaboration meeting. Scientific advisers to the Government of India (collaborators from National Institute of Nutrition) were present at the meetings and instrumental in the design and framing of the grant proposal. Building on discussions and pilot work presented at the collaboration meeting, a grant proposal funding application has been submitted (currently pending funding decision).
Start Year 2019
 
Description Novel collaboration of UK and Indian scientists to elucidate metabolomic pathways of dietary risks in Indians 
Organisation Yenepoya University
Country India 
Sector Academic/University 
PI Contribution As PI of the grant, I initiated the collaboration and brought all of the teams on board. My team coordinated a 2-day collaboration meeting in Hyderabad (Novemeber 2019), where we developed a plan for a program of research aiming to elucidate metabolomic pathways between diet and cardiovascular risk in Indians. I led on the coordination and writing of the grant proposal which arose from the meeting.
Collaborator Contribution All collaborators contributed subject-specific knowledge and expertise towards conceptualizing and writing the grant proposal. Collaborators from National Institute of Nutrition and Yenepoya University collected samples and conducted pilot metabolomic analyses to inform development of the proposal. Collaborators from Public Health Foundation of India and London School of Hygiene and Tropical Medicine conducted epidemiological analyses of existing data and presented findings at the meeting.
Impact Three manuscripts are under preparation relating to pilot work and discussions from the collaboration meeting. Scientific advisers to the Government of India (collaborators from National Institute of Nutrition) were present at the meetings and instrumental in the design and framing of the grant proposal. Building on discussions and pilot work presented at the collaboration meeting, a grant proposal funding application has been submitted (currently pending funding decision).
Start Year 2019
 
Description Community engagement with participants from the APCAPS study site in rural India 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact We held community consultation and engagement meetings with members of the APCAPS study community (which will be the site of data collection in the proposed grant), to understand the local communities views and knowledge around dietary risks for cardiovascular disease, and their own research priorities in this area, to feed back into our grant proposal. We also used this opportunity to gauge the community members' interest and commitment in study participation, which was very high.
Year(s) Of Engagement Activity 2019,2020