Metabolome and microbiome alterations related to short-term feeding of a micronutrient-fortified, high-quality legume protein-based food product to stunted school age children: A randomized controlled pilot trial

Authors: VARKEY, ANEESIA - St John'S National Academy Of Health Sciences; DEVI, SARITA - St John'S National Academy Of Health Sciences; MUKHOPADHYAY, ARPOTA - St John'S National Academy Of Health Sciences; KAMAT, NAMRATA - St John'S National Academy Of Health Sciences; PAULINE, MARIA - St John'S National Academy Of Health Sciences; DHARMAR, MADA - Uc Davis Medical Center; HOLT, ROBERTA - University Of California, Davis; Allen, Lindsay - A; THOMAS, TINKU - St John'S National Academy Of Health Sciences; KEEN, CARL - University Of California, Davis; KURPAD, ANURA - St John'S National Academy Of Health Sciences

Submitted to: Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/14/2020
Publication Date: 2/24/2020
Citation: Varkey, A., Devi, S., Mukhopadhyay, A., Kamat, N.G., Pauline, M., Dharmar, M., Holt, R., Allen, L.H., Thomas, T., Keen, C.I., Kurpad, A. 2020. Metabolome and microbiome alterations related to short-term feeding of a micronutrient-fortified, high-quality legume protein-based food product to stunted school age children: A randomized controlled pilot trial. Clinical Nutrition. https://doi.org/10.1016/j.clnu.2020.02.018.
DOI: https://doi.org/10.1016/j.clnu.2020.02.018

Interpretive Summary: Stunting in children is associated with undernutrition and may be ameliorated by the provision of high-quality foods that provide protein and micronutrients. Addressing this problem in lower social economic environments requires, in part, affordable and scalable food-based solutions with efficacious food products. Towards this end, biochemical/metabolic indicators for fast-throughput screening of foods and their components are desired. A highly acceptable and economical micronutrient-fortified food product with different levels of legume protein was provided to stunted Indian children for one month, to determine change in their linear growth and explore associated biochemical, metabolomic and microbiome indicators. The approach was to conduct a randomized controlled pilot trial with 100 stunted children (6 to 10 years of age) to elucidate metabolic and microbiome-based biomarkers associated with linear growth. They were randomized into 4 groups receiving 6, 8, 10 or 12 g of a legume-based protein supplement per day for one month. Anthropometry, blood biochemistry, amino acids and acyl carnitines measured with metabolomics, and the fecal microbiome were measured before and after the feeding trial. No significant differences were observed between groups in height, height-for-age Z-score (HAZ) or BMI-for-age Z-score (BAZ); however, 38 serum metabolites were altered significantly (P < 0.1) in response to the interventions. IGF-1 (Insulin-like Growth Factor-1) was positively ('> 0.2, P = 0.02), while serine and ornithine (P < -0.2, P = 0.08) were negatively, associated with change in height. Leucine, isoleucine and valine positively correlated (P = 0.011, 0.023 and 0.007 respectively) with change in BAZ. Three Operational Taxonomic Units of bacteria in the fecal microbiome, belonging to Bacteroidetes and Firmicutes (VIP score >1.5), were significantly correlated with change in height. We conclude that in this pilot trial, a number of fasting serum metabolomic and fecal microbiome signatures were associated with linear growth after a short-term dietary intervention. The alterations of these markers should be validated in long-term dietary intervention trials as potential screening indicators towards the development of food products that favor growth. This trial was registered at www.ctri.nic.in as CTRI/2016/12/007564.

Technical Abstract: Stunting in children is a comorbid condition in undernutrition that may be ameliorated by the provision of high-quality foods that provide protein and micronutrients. Addressing this problem in lower social economic environments requires, in part, affordable and scalable food-based solutions with efficacious food products. Towards this end, biochemical/metabolic indicators for fast-throughput screening of foods and their components are desired. A highly acceptable and economical micronutrient-fortified food product with different levels of legume protein was provided to stunted Indian children for one month, to determine change in their linear growth and explore associated biochemical, metabolomic and microbiome indicators. Methods A randomized controlled pilot trial was conducted with 100 stunted children (6–10 years of age) to elucidate metabolic and microbiome-based biomarkers associated with linear growth. They were randomized into 4 groups receiving 6, 8, 10 or 12 g of legume-based protein for one month. Anthropometry, blood biochemistry, aminoacidomics, acylcarnitomics and fecal microbiome were measured before and after feeding. Results No significant differences were observed between groups in height, height-for-age Z-score (HAZ) or BMI-for-age Z-score (BAZ); however, 38 serum metabolites were altered significantly (Bonferroni adjusted P< 0.1) in response to the interventions. IGF-1 (Insulin like Growth Factor-1) was positively (P >0.2, P =0.02), while serine and ornithine (' <-0.2, P = 0.08) were negatively associated with change in height. Leucine, isoleucine and valine positively correlated (P = 0.011, 0.023 and 0.007 respectively) with change in BAZ. Three Operational Taxonomic Units belonging to Bacteroidetes and Firmicutes (VIP score > 1.5) were significantly correlated with change in height. Conclusions In this pilot trial, a number of fasting serum metabolomic and fecal microbiome signatures were associated with linear growth after a short-term dietary intervention. The alterations of these markers should be validated in long-term dietary intervention trials as potential screening indicators towards the development of food products that favor growth. This trial was registered at www.ctri.nic.in as CTRI/2016/12/007564.