Exploring the Effect of Legume Enriched Feeds on Gut Health In Undernourished Children
Lead Research Organisation:
Imperial College London
Department Name: Metabolism, Digestion and Reproduction
Abstract
BACKGROUND:
Severe acute malnutrition (SAM) is one of the most common underlying morbidity and mortality cause in children worldwide, with a prevalence of 1.5 million deaths annually, occurring due to changes in gut microbial balance and intestinal mucosal integrity. Currently, milk-based feeds are the standard recommended formulae by WHO in children with SAM, which can however cause osmotic diarrhoea. Therefore, by removing lactose and replacing with better tolerated simple carbohydrates, would be a more beneficial alternative in preventing or improving symptoms of diarrhea.
A plethora of studies suggest that small chain fatty acids (SCFA), which are produced primarily from microbial fermentation process of dietary fibre, appear to be key mediators of the beneficial effect promoted by the gut microbiota, such as maintaining health via regulation of the immune system. Legumes, which contain a mixture of different types of non-digestible fermentable carbohydrates, have been shown to increase microbial communities that enhance the production of SCFA, therefore posing a promising nutritional therapy against SAM.
Even though there has been an increase on the number of studies focusing on understanding gut function, there is a gap in translating findings clinically, mainly due to limitations associated with conventional culture platforms in supporting co-culture of living epithelium cells with microbes for more than a day. Recent technological advancements on cell culture systems, have enabled the development of experimental chip models of human intestine that allow analysis of gut pathophysiology in the presence of living microbiome for several days.
HYPOTHESIS: We hypothesized that introduction of lactose free, legume enriched feed in the early management of SAM affected children that are admitted to the hospital, could improve gut function and therefore, safely and cost effectively improve clinical outcomes globally.
METHODOLOGY: The hypothesis will be assessed by using data and samples from a completed interventional study on children with SAM, receiving legume-based, dairy-free feed vs current WHO standard feed. The effect of the feeds on gut integrity will be investigated on the basis of host-gut metabolic interactions, microbiota diversity and gut inflammation by using a combination of spectroscopic and gene sequencing techniques. In addition, we will also attempt to create an in vitro malnourished model of human intestine by using a commercial microfluidic gut-on-a-Chip platform in order to understand SAM pathophysiology and gut signaling in a near physiological setting.
RESEARCH OUTCOMES: This study will bring new evidence and potential therapeutic solutions on the field of SAM, by the modulation of gut microbiome, which could promote gut mucosal function recovery and enhance infection resilience, leading ultimately to the reduction of morbidity and mortality rates worldwide.
Severe acute malnutrition (SAM) is one of the most common underlying morbidity and mortality cause in children worldwide, with a prevalence of 1.5 million deaths annually, occurring due to changes in gut microbial balance and intestinal mucosal integrity. Currently, milk-based feeds are the standard recommended formulae by WHO in children with SAM, which can however cause osmotic diarrhoea. Therefore, by removing lactose and replacing with better tolerated simple carbohydrates, would be a more beneficial alternative in preventing or improving symptoms of diarrhea.
A plethora of studies suggest that small chain fatty acids (SCFA), which are produced primarily from microbial fermentation process of dietary fibre, appear to be key mediators of the beneficial effect promoted by the gut microbiota, such as maintaining health via regulation of the immune system. Legumes, which contain a mixture of different types of non-digestible fermentable carbohydrates, have been shown to increase microbial communities that enhance the production of SCFA, therefore posing a promising nutritional therapy against SAM.
Even though there has been an increase on the number of studies focusing on understanding gut function, there is a gap in translating findings clinically, mainly due to limitations associated with conventional culture platforms in supporting co-culture of living epithelium cells with microbes for more than a day. Recent technological advancements on cell culture systems, have enabled the development of experimental chip models of human intestine that allow analysis of gut pathophysiology in the presence of living microbiome for several days.
HYPOTHESIS: We hypothesized that introduction of lactose free, legume enriched feed in the early management of SAM affected children that are admitted to the hospital, could improve gut function and therefore, safely and cost effectively improve clinical outcomes globally.
METHODOLOGY: The hypothesis will be assessed by using data and samples from a completed interventional study on children with SAM, receiving legume-based, dairy-free feed vs current WHO standard feed. The effect of the feeds on gut integrity will be investigated on the basis of host-gut metabolic interactions, microbiota diversity and gut inflammation by using a combination of spectroscopic and gene sequencing techniques. In addition, we will also attempt to create an in vitro malnourished model of human intestine by using a commercial microfluidic gut-on-a-Chip platform in order to understand SAM pathophysiology and gut signaling in a near physiological setting.
RESEARCH OUTCOMES: This study will bring new evidence and potential therapeutic solutions on the field of SAM, by the modulation of gut microbiome, which could promote gut mucosal function recovery and enhance infection resilience, leading ultimately to the reduction of morbidity and mortality rates worldwide.
Organisations
People |
ORCID iD |
| Isabel Garcia-Perez (Primary Supervisor) | |
| Agklinta Kiosia (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/R513052/1 | 01/10/2018 | 30/09/2023 | |||
| 2289150 | Studentship | EP/R513052/1 | 02/09/2019 | 28/02/2023 | Agklinta Kiosia |
| Description | We have supportive evidence that our nutritional feed containing legume based ingredients such as chickpea, is safe and well tolerated by the gut of severely undernourished children, in low income countries, in a clinical setting. Comparing our feed to the WHO standard feed currently given, we have shown that our chickpea based feed performs equally well in various anthropometric and clinical parameters such as weight gain and mortality. Trends, however suggest that the chickpea based feed, had less re-admissions and the weight gain was more steady and maintained better overtime, compared to the WHO feed. Furthermore, we are exploring the impact of the feeds on the gut health and overall well-being of the children by assessing specific gut bacteria and molecules that are associated with optimal health and anti-inflammatory prophylactic effects, that maintain a healthy gut, therefore improving quality of life, in the long run. The benefit of our legume enriched feed over the current standard feed from a socioeconomic point of view, lays on the fact that our feed can be produced locally from locally sourced ingredients, hence, giving the opportunity to the locals for economic growth. Some aspects of the project are still under analysis and investigation. |
| Exploitation Route | Once we have established the primary and secondary outcomes of the study, the next phase will include making informed decisions on a new study on a greater number of participants and potentially explore additional elements of the topic by utilising new technology to gain as more mechanistic depth as possible in terms of biological pathways involved. Another element which the team is currently looking at, is refining the feed in terms of formulation (texture), from a paste to a liquid base formula, which will be easier for children to consume. We are hoping that our findings will inspire more research groups to investigate the role of sustainable and locally sourced therapeutic feeds, such as legumes that have been associated with a plethora of health benefits, such as increase of the number of good gut bacteria that improve overall health by reducing inflammation and promoting immune response to maintain a healthy status. As long term goals, we are hoping that our research will inspire funding bodies and scientists alike , to increase their contribution in order to minimise childhood mortality and and hunger. |
| Sectors | Agriculture, Food and Drink,Communities and Social Services/Policy,Education,Healthcare,Government, Democracy and Justice,Manufacturing, including Industrial Biotechology |
| Description | Some of the data from this trial have been used in order to make improvements on the nutritional feed, with respect to feed formulation, which has led in the collaboration with a local feed manufactory company in Uganda which is a positive outcome for the local economic growth. Raw materials have been also sourced locally. In addition, hiring local clinical stuff for the clinical trial is another positive outcome as it contributes towards the education and training of local clinical staff based on good clinical practices. |
| First Year Of Impact | 2021 |
| Sector | Agriculture, Food and Drink,Communities and Social Services/Policy,Healthcare,Manufacturing, including Industrial Biotechology |
| Impact Types | Societal,Economic |