Guillermo E. Sanchez and Glenn H. Sullivan

January 2018

Environmental enteropathy dysfunction (EED), a chronic intestinal inflammatory condition caused by repeated acute infections (1) reduces host immunity and enhances stunting (chronic malnutrition) in afflicted young children.  Characterized by intestinal inflammation, blunting of the intestinal villi, reduced intestinal absorption capacity and impaired membrane permeability (barrier function) (2,3), EED can have a significant impact on lineal growth during early childhood.  EED is exacerbated by poor nutrition, unsanitary environmental conditions, contaminated water, poor hygiene and inadequate child care, requiring a multi-approach strategy to manage the disease.  Some of these tactics include (i) improved sanitation, hygiene and clean uncontaminated water, (ii) improved breastfeeding and nutrition, incorporating the use of prebiotics and probiotics as well as nutrient supplements and, (iii) use of antibiotics and anti-inflammatory agents to manage infections and improve nutrient absorption (4).

The role of an impaired microbiome in children with EED is an interesting current area of research, as it has been demonstrated that the development of a ‘healthy’ gut microbiota undergoes changes among malnourished children, compared to healthy siblings (5).  Other studies have shown that growth failure is associated to intestinal inflammation, a key component of EED (6).  Furthermore, recent studies suggest that linear growth can be associated with changes in the gut microbiota of young children, with less diverse microbiota associated with stunting severity (7).

Microorganisms with beneficial effects on the health of individuals, when ingested at sufficient amounts, are known as probiotics.  Prebiotics are carbohydrates that stimulate the growth of specific probiotic species; synbiotics result from the combination of a prebiotics and probiotics (8).  Different animal models have been used to study the prebiotic and bioactive characteristics of rice bran (RB) or its derivatives.  In rats for example, enzyme treated prebiotic products developed from RB have been shown to improve inflammatory bowel disease (9).  In gnotobiotic pigs colonized with probiotics, the consumption of RB prevented human rotavirus diarrhea, prevented epithelial damage and promoted growth (10).   RB has also been shown to improve lipid levels, ameliorate chronic diseases such as type II diabetes, metabolic syndrome, cardiovascular disease, and exhibited cancer fighting properties (11).  RB also contains bioactive (not necessarily bioavailable) nutraceutical components including polyphenols, fatty acids, flavonoids, amino acids and peptides (12, 13).  Moreover, recent studies using metabolomics identified 453 metabolites, including vitamins, amino acids, peptides, carbohydrates, lipids and cofactors which probably work synergistically and confer RB its functional food properties that help reduce the risk of chronic and infectious diseases (14).

The use of RB as weaning component in complementary food products after the exclusive breastfeeding period is of interest, especially in resource poor areas where animal protein is expensive or scarce (11).  The high caloric content of RB, along with its high quality hypoallergenic protein (15) and prebiotic properties make it an attractive option as a complementary functional food that could be of importance in impoverished and nutrient deficient regions.  For example, the potential prevention or mitigation of human rotavirus diarrhea in preschool aged children shown by rice bran in animal models can also be of great importance, as HRV-induced diarrhea continues to be a major morbidity factor in developing countries.  However, the problem with RB in its natural state remains the lack of bioavailability in the human gastrointestinal tract.

Recently, a patented rice bran derivative obtained through combined enzymatic extraction of carbohydrase’s and proteases has been developed (16). Trademarked NutraLac®, this rice bran enzymatic extract (RBEE) exhibits unique characteristics that enhances bioavailability and its potential as a functional food.  Despite its interesting nutritional composition, rice bran’s potential use as a functional food is limited by high insolubility of its protein as well as the integrity of its nutraceutical components, particularly referring to the phenolic fraction (17).  As in other RBEE’s (18) and due to the use of proteases (that solubilize and hydrolyze the initial insoluble proteins) NutraLac® shows an increase of soluble proteins, peptides, and free amino acids with physical properties different from those of RB, but at a significantly higher level than other RB extracts (19).  The changes in NutraLac’s® protein structure drastically modify the water solubility and increase nutritional functionality.  As similarly shown in other RBEE studies (20), NutraLac® also contains higher concentrations of bioactive nutraceutical phytomolecules and pharmacological compounds, including tocopherols, tocotrienols (Vitamin E complex) as well as gamma-oryzanol and other phytosterols (Annex 1).

The increased concentration and bioavailability of peptides and other bioactive phytochemicals in NutraLac®,  make it a functional food with great potential as an adjuvant in the treatment of chronic diseases such as EED and protein-calorie malnourishment in young children.


  1. Trepan, I., Kelly, P., Shaikh, N., & Manary, M. J. (2016). New insights into environmental enteric dysfunction. Archives of disease in childhood, archdischild-2015.
  2. Crane, R. J., Jones, K. D., & Berkley, J. A. (2015). Environmental enteric dysfunction: an overview. Food and nutrition bulletin36(1_suppl1), S76-S87.
  3. Syed, S., Ali, A., & Duggan, C. (2016). Environmental Enteric Dysfunction in Children. Journal of pediatric gastroenterology and nutrition63(1), 6-14.
  4. Owino, V., Ahmed, T., Freemark, M., Kelly, P., Loy, A., Manary, M., & Loechl, C. (2016). Environmental enteric dysfunction and growth failure/stunting in global child health. Pediatrics138(6), e20160641.
  5. Smith, M. I., Yatsunenko, T., Manary, M. J., Trehan, I., Mkakosya, R., Cheng, J., … & Liu, J. (2013). Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science339(6119), 548-554.
  6. Kosek, M., Haque, R., Lima, A., Babji, S., Shrestha, S., Qureshi, S., … & Guerrant, R. L. (2013). Fecal markers of intestinal inflammation and permeability associated with the subsequent acquisition of linear growth deficits in infants. The American journal of tropical medicine and hygiene88(2), 390-396.
  7. Gough, E. K., Stephens, D. A., Moodie, E. E., Prendergast, A. J., Stoltzfus, R. J., Humphrey, J. H., & Manges, A. R. (2015). Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota. Microbiome3(1), 24.
  8. Alou, M. T., Lagier, J. C., & Raoult, D. (2016). Diet influence on the gut microbiota and dysbiosis related to nutritional disorders. Human Microbiome Journal1, 3-11.,
  9. Komiyama, Y., Andoh, A., Fujiwara, D., Ohmae, H., Araki, Y., Fujiyama, Y., … & Kanauchi, O. (2011). New prebiotics from rice bran ameliorate inflammation in murine colitis models through the modulation of intestinal homeostasis and the mucosal immune system. Scandinavian journal of gastroenterology46(1), 40-52.
  10. Yang, X., Twitchell, E., Li, G., Wen, K., Weiss, M., Kocher, J., … & Yuan, L. (2015). High protective efficacy of rice bran against human rotavirus diarrhea via enhancing probiotic growth, gut barrier function, and innate immunity. Scientific reports5.
  11. Borresen, E. C., & Ryan, E. P. (2014). Rice bran: a food ingredient with global public health opportunities. In: Watson RR, Preedy VR, Zibadi S, eds. Wheat and Rice in Disease Prevention and Health. 1st Academic Press; p. 301-310.
  12. Huang, Y. P., & Lai, H. M. (2016). Bioactive compounds and antioxidative activity of colored rice bran. journal of food and drug analysis24(3), 564-574.
  13. Ryan, E. P. (2011). Bioactive food components and health properties of rice bran. Journal of the American Veterinary Medical Association238(5), 593-600.
  14. Zarei, I., Brown, D. G., Nealon, N. J., & Ryan, E. P. (2017). Rice Bran Metabolome Contains Amino Acids, Vitamins & Cofactors, and Phytochemicals with Medicinal and Nutritional Properties. Rice10(1), 24.
  15. Khan, S. H., Butt, M. S., Anjum, F. M., & Sameen, A. (2011). Quality evaluation of rice bran protein isolate-based weaning food for preschoolers. International journal of food sciences and nutrition62(3), 280-288.
  16. Lynch, I. E., Sullivan, G. H., & Miller, L. R. (2015). Nutritionally enhanced isolate from stabilized rice bran and method of production. S. Patent No. 8,945,642. Washington, DC: U.S. Patent and Trademark Office.
  17. Justo, M. L., Rodriguez–Rodriguez, R., Claro, C. M., De Sotomayor, M. A., Parrado, J., & Herrera, M. D. (2013). Water-soluble rice bran enzymatic extract attenuates dyslipidemia, hypertension and insulin resistance in obese Zucker rats. European journal of nutrition52(2), 789-797.
  18. Parrado, J., Miramontes, E., Jover, M., Gutierrez, J. F., de Terán, L. C., & Bautista, J. (2006). Preparation of a rice bran enzymatic extract with potential use as functional food. Food Chemistry98(4), 742-748.
  19. Sullivan, G.H. ‘All rice bran derivatives are not equal’. Quintessence Nutraceuticals Position Paper, 2017.
  20. Vallabha, V. S., Indira, T. N., Lakshmi, A. J., Radha, C., & Tiku, P. K. (2015). Enzymatic process of rice bran: a stabilized functional food with nutraceuticals and nutrients. Journal of food science and technology52(12), 8252-8259.