Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Nutrition in acute and chronic diseases

The effect of enteral stimulation on the immune response of the intestinal mucosa and its application in nutritional support


The intestine plays a fundamental role as a regulator of the mucosal immune response, mostly through the production and secretion of secretory Immunoglobulin A (sIgA) by the gut-associated lymphoid tissue (GALT). Enteral stimulation, a balance between the commensal microbiota and pathogenic microorganisms, in addition to an adequate nutritional status is required for the optimal immune function of the intestine. Fasting subjects or those supported only with parenteral nutrition, show a progressive anatomical and physiological deterioration of the GALT, triggering a series of alterations resulting in a decrease in the intestinal immune response, modification in the type of microbiota, and changes that lead to or aggravate malnutrition. Patients with malnutrition present an increase in the rate of nosocomial infections, hospital length of stay, and mortality. An adequate nutritional assessment at hospital admission and avoiding long periods of fasting are paramount to prevent these unfavorable outcomes. Herein, we present a mini-state of the art review on the role and importance of enteral stimulation by GALT-mediated immune response.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Mechanism of IgAs production in GALT in response to a pathogen.


  1. 1.

    Kang W, Kudsk KA. Is there evidence that the gut contributes to mucosal immunity in humans? J Parenter Enter Nutr. 2007;31:246–58.

    CAS  Article  Google Scholar 

  2. 2.

    Cesta MF. Normal structure, function, and histology of mucosa-associated lymphoid tissue. Toxicol Pathol. 2006;34:599–608.

    PubMed  Article  Google Scholar 

  3. 3.

    Elmore SA. Enhanced histopathology of mucosa-associated lymphoid tissue. Toxicol Pathol. 2006;34:687–96.

    PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Fukatsu K, Kudsk KA. Nutrition and gut immunity. Surg Clin North Am. 2011;91:755–70.

    PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    Pierre JF. Gastrointestinal immune and microbiome changes during parenteral. Am J Physiol - Gastrointest Liver Physiol. 2017;312:G246–56.

    PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    Pierre JF, Busch RA, Kudsk KA. The gastrointestinal immune system: implications for the surgical patient. Curr Probl Surg. 2016;53:11–47.

    PubMed  Article  Google Scholar 

  7. 7.

    Jonker MA, Hermsen JL, Sano Y, Heneghan AF, Lan J, Kudsk KA. Small intestine mucosal immune system response to injury and the impact of parenteral nutrition. Surg [Internet] 2012;151:278–86.

    Article  Google Scholar 

  8. 8.

    Szefel J, Kruszewski WJ, Buczek T. Enteral feeding and its impact on the gut immune system and intestinal mucosal barrier. Prz Gastroenterol. 2015;10:71–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Gommerman JL, Rojas OL, Fritz JH. Re-thinking the functions of IgA+plasma cells. Gut Microbes. 2015;5:652–62.

    Article  Google Scholar 

  10. 10.

    Woof JM, Ken MA. The function of immunoglobulin A in immunity. J Pathol. 2006;208:270–82.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Anastasilakis CD, Ioannidis O, Gkiomisi AI, Botsios D. Artificial nutrition and intestinal mucosal barrier functionality. Digestion. 2013;88:193–208.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Suzuki K, Fagarasan S. How host-bacterial interactions lead to IgA synthesis in the gut. Trends Immunol. 2008;29:523–31.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Pabst O. New concepts in the generation and functions of IgA. Nat Rev Immunol. 2012;12:821–32.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Kudsk KA, Croce MA, Fabian TC, Minard G, Tolley EA, Poret HA, et al. Enteral versus parenteral feeding effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg. 1992;215:503–13.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Sano Y, Gomez FE, Kang W, Lan J, Maeshima Y, Hermsen JL, et al. Intestinal polymeric immunoglobulin receptor is affected by type and route of nutrition. J Parenter Enter Nutr. 2007;31:356–7.

    Article  Google Scholar 

  16. 16.

    Hermsen JL, Sano Y, Gomez FE, Maeshima Y, Kang W, Kudsk KA. Parenteral nutrition inhibits tumor necrosis factor- α-mediated IgA response to injury. Surg Infect (Larchmt) 2008;9:33–40.

    Article  Google Scholar 

  17. 17.

    Heneghan AF, Pierre JF, Tandee K, Shanmuganayagam D, Wang X, Reed JD, et al. Parenteral nutrition decreases paneth cell function and intestinal bactericidal activity while increasing susceptibility to bacterial enteroinvasion. J Parenter Enter Nutr. 2014;38:817–24.

    CAS  Article  Google Scholar 

  18. 18.

    Ikeda S, Kudsk KA, Fukatsu K, Johnson CD, Le T, Reese S, et al. Enteral feeding preserves mucosal immunity despite in vivo MAdCAM-1 blockade of lymphocyte homing. Ann Surg. 2003;237:677–85.

    PubMed  PubMed Central  Google Scholar 

  19. 19.

    Li J, Kudsk KA, Gocinski B, Dent D, Glezer J, Langkamp-Henken B, et al. Effects of parenteral and enteral nutrition on gut-associated lymphoid tissue. J Trauma - Inj Infect Crit Care. 1995;39:44–51.

    CAS  Article  Google Scholar 

  20. 20.

    Hermsen JL, Sano Y, Kudsk KA. Food fight! Parenteral nutrition, enteral stimulation and gut-derived mucosal immunity. Langenbeck’s Arch Surg. 2009;394:17–30.

    Article  Google Scholar 

  21. 21.

    Fukatsu K. Role of nutrition in gastroenterological surgery. Ann Gastroenterol Surg. 2019;3:160–8.

    PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Fukatsu K. Impact of the feeding route on gut mucosal immunity. Curr Opin Clin Nutr Metab Care. 2014;17:164–70.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Elke G, van Zanten ARH, Lemieux M, McCall M, Jeejeebhoy KN, Kott M, et al. Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials. Crit Care/ 2016;20:1–14.

    Google Scholar 

  24. 24.

    McCoy KD, Burkhard R, Geuking MB. The microbiome and immune memory formation. Immunol Cell Biol. 2019;97:625–35.

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Huus KE, Bauer KC, Brown EM, Bozorgmehr T, Woodward SE, Serapio-Palacios A, et al. Commensal bacteria modulate immunoglobulin a binding in response to host nutrition. Cell Host Microbe. 2020;27:1–13.

    Article  CAS  Google Scholar 

  26. 26.

    Miyasaka EA, Feng Y, Poroyko V, Falkowski NR, Erb-Downward J, Gillilland MG, et al. Total parenteral nutrition–associated lamina propria inflammation in mice is mediated by a MyD88-dependent mechanism. J Immunol. 2013;190:6607–15.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Amarasinghe JJ, D’Hondt RE, Waters CM, Mantis NJ. Exposure of Salmonella enterica serovar typhimurium to a protective monoclonal IGA triggers exopolysaccharide production via a diguanylate cyclase-dependent pathway. Infect Immun. 2013;81:653–64.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Cullender TC, Chassaing B, Janzon A, Kumar K, Muller CE, Werner JJ, et al. Innate and adaptive immunity interact to quench microbiome flagellar motility in the gut. Cell Host Microbe. 2013;14:571–81.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. 29.

    McClave SA, Taylor BE, Martindale RG, Warren MM, Johnson DR, Braunschweig C, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically Ill patient: society of critical care medicine (SCCM) and American society for parenteral and enteral nutrition (A.S.P.E.N.). J Parenter Enter Nutr. 2016;40:159–211.

    CAS  Article  Google Scholar 

  30. 30.

    Okamoto K, Fukatsu K, Hashiguchi Y, Ueno H, Shinto E, Moriya T, et al. Lack of preoperative enteral nutrition reduces gut-associated lymphoid cell numbers in colon cancer patients: a possible mechanism underlying increased postoperative infectious complications during parenteral nutrition. Ann Surg. 2013;258:1059–64.

    PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Patel JJ, Kozeniecki M, Biesboer A, Peppard W, Ray AS, Thomas S, et al. Early trophic enteral nutrition is associated with improved outcomes in mechanically ventilated patients with septic shock: a retrospective review. J Intensive Care Med. 2016;31:471–7.

    PubMed  Article  Google Scholar 

  32. 32.

    Gustafsson UO, Scott MJ, Schwenk W, Demartines N, Roulin D, Francis N, et al. Guidelines for perioperative care in elective colonic surgery: Enhanced recovery after surgery (ERAS®) society recommendations. World J Surg. 2013;37:259–84.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  33. 33.

    Higashizono K, Fukatsu K, Watkins A, Watanabe T, Noguchi M, Ri M, et al. Influences of short-term fasting and carbohydrate supplementation on gut immunity and mucosal morphology in mice. J Parenter Enter Nutr. 2019;43:516–24.

    CAS  Article  Google Scholar 

  34. 34.

    Bourke CD, Berkley JA, Prendergast AJ. Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol. 2016;37:386–98.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Correia MITD, Perman MI, Waitzberg DL. Hospital malnutrition in Latin America: a systematic review. Clin Nutr. 2017;36:958–67.

    PubMed  Article  Google Scholar 

  36. 36.

    Cederholm T, Jensen GL, Correia MITD, Gonzalez MC, Fukushima R, Higashiguchi T. et al. GLIM criteria for the diagnosis of malnutrition – A consensus report from the global clinical nutrition community. Clin Nutr. 2019;38:1–9.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Pérez Romero MT, Serralde-Zuniga AE, Reyes Ramírez AL, del C, Alfonso Baruch E, Gulías Herrero A. et al. Prevalence of malnutrition at admission in hospitalized adults at INCMNSZ in Mexico City. Rev Mex Endocrinol Metab y Nutr. 2017;4:12–6.

    Google Scholar 

  38. 38.

    Waitzberg DL, Ravacci GR, Raslan M. Desnutrición hospitalaria. Nutr Hosp. 2011;26:254–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Rangel AG, Sepúlveda FR, Domínguez RS, Maldonado GM. Evaluación del estado nutricional y su impacto en pacientes post operados de anastomosis intestinal. Nutrición y fuga anastomosis. Nutr Clin y Diet Hosp. 2016;36:82–8.

    Google Scholar 

  40. 40.

    Morris HJ, Carrillo OV, Llauradó G, Alonso ME, Bermúdez RC, Lebeque Y, et al. Effect of starvation and refeeding on biochemical and immunological status of Balb/c mice: an experimental model of malnutrition. Immunopharmacol Immunotoxicol. 2011;33:438–46.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T, Trehan I, et al. Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Sci Transl Med. 2015;7:276ra24.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  42. 42.

    Lochs H, Dejong C, Hammarqvist F, Hebuterne X, Leon-Sanz M, Schütz T, et al. ESPEN guidelines on enteral nutrition: gastroenterology. Clin Nutr. 2006;25:260–74.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Hernández Centeno JR, Fernández Galicia JC, González Bravo F, Ramírez Barba EJ, Zavala Martín J, Montiel Ramírez AE, et al. Inicio temprano de la alimentación enteral en pacientes con reconexión intestinal. Nutr Clin y Diet Hosp. 2013;33:18–22.

    Google Scholar 

  44. 44.

    Reddy V, Raghuramulu N, Bhaskaram C. Secretory IgA in protein-calorie malnutrition. Arch Dis Child. 1976;51:871–4.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Elmadfa I, Meyer AL. The role of the status of selected micronutrients in shaping the immune function. Endocr, Metab Immune Disord - Drug Targets. 2019;19:1100–15.

    CAS  Article  Google Scholar 

  46. 46.

    Kudsk KA, Hermsen JL, Genton L, Faucher L, Gomez FE. Injury stimulates an innate respiratory immunoglobulin a immune response in humans. J Trauma - Inj Infect Crit Care. 2008;64:316–23.

    Article  Google Scholar 

  47. 47.

    Sano Y, Hermsen JL, Kang W, Gomez FE, Lan J, Maeshima Y, et al. Parenteral nutrition maintains pulmonary IgA antibody transport capacity, but not active transport, following injury. Am J Surg. 2009;198:105–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Kondrup J, Ramussen HH, Hamberg O, Stanga Z, Camilo M, Richardson R, et al. Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr. 2003;22:321–36.

    PubMed  Article  Google Scholar 

  49. 49.

    Heyland DK, Dhaliwal R, Jiang X, Day AG. Identifying critically ill patients who benefit the most from nutrition therapy: the development and initial validation of a novel risk assessment tool. Crit Care. 2011;15:R268.

    PubMed  PubMed Central  Article  Google Scholar 

  50. 50.

    The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. N. Engl J Med. 1991;325:525–32.

    Article  Google Scholar 

Download references


This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information




GQO, AESZ, and GGS were responsible for the main idea. GQO conducted the search of the studies and extract the information. GQO, MFRP, JGPC, AESZ, and GGS wrote the manuscript and designed the figure and table, and AESZ, GGS, and JGPC reviewed the final script.

Corresponding author

Correspondence to Aurora E Serralde-Zúñiga.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Quiroz-Olguín, G., Gutiérrez-Salmeán, G., Posadas-Calleja, J.G. et al. The effect of enteral stimulation on the immune response of the intestinal mucosa and its application in nutritional support. Eur J Clin Nutr (2021).

Download citation


Quick links