Prior research has demonstrated that children from low- and middle-income countries have a specific microbiome taxa that change in the setting of malnutrition, and such changes may contribute to malnutrition. This study from Bangladesh recruited children between 12 and 18 months of age with moderate acute malnutrition. Such children were randomized to consume either a newly developed microbiota-directed complementary food (MDCF) or a standard ready-to-use supplementary food (RUSF) for three months. The MDCF used in this study was MDCF-2 which is a new formulation that previously has been shown to change the microbiome to beneficial taxa. Anthropometric data was measured every 15 days, and fecal samples were obtained one month after the intervention. Besides anthropometric data, all patients underwent plasma proteomic profiling and gut microbiota determination.
A total of 123 subjects were enrolled (61 received MDCF-2 and 62 received RUSF). No was present regarding anthropometrics and social demographics between the two treatment groups. Both weight-for-length z scores and weight-for-age z scores significantly improved in the MDCF-2 group compared to the RUSF group. Plasma protein analysis showed that 714 proteins significantly increased or decreased in patients receiving MDCF-2 versus 82 proteins which significantly increased or decreased in patients receiving RUSF. Specific proteins that increased significantly in the MDCF-2 group included intermediate layer protein 2 (which improves articular cartilage formation), thrombospondin-4 (which helps develop bone and skeletal muscle), and SFRP4 (which is an osteoclast inhibitor). Fecal analysis demonstrated that 23 bacterial taxa (identified by amplicon sequence variants) were significantly associated with weight-forlength z scores (21 positively associated; 2 negatively associated). Interestingly, 5 of these taxa promoting growth had been identified previously in gnotobiotic mouse studies. Finally, these specific 21 bacterial taxa associated with increased weightfor- length z scores were significantly increased in children receiving MDCF-2 compared to children receiving RUSF and had a positive correlation with 70 plasma proteins associated with improving weight-for-length z scores.
This study demonstrates that changing the fecal microbiome via dietary manipulation may reverse the effects of malnutrition. This finding is intriguing as such effects also could occur in the setting of various types of intestinal inflammation. It is interesting to note that the significant improvements in malnutrition in children receiving MDCF-2 occurred despite this formulation having less caloric density compared to RUSF.
Chen R, Mostafa I, Hibberd M, Das S, Mahfuz M, Naila N, Islam M, Huq S, Alam A, Zaman M, Raman A, Webber D, Zhou C, Sundaresan V, Ahsan K, Meier M, Barratt M, Ahmed T, Gordon J. A microbiotadirected food intervention for undernourished children. N Engl J Med 2021; 384: 1517-1528.