Enteral nutrition and the gut microbiome
by Annina Whipp, Registered Dietitian
Annina is a UK Registered Dietitian with experience in gastrointestinal disorders, diabetes and weight management and in both adult and paediatric settings.
Enteral nutrition (EN) refers to any method of feeding which uses the gastrointestinal tract to deliver some or all of a person’s nutritional requirements.1 British Association for Parenteral and Enteral Nutrition (BAPEN). Enteral Nutrition. Available from: https://www.bapen.org.uk/nutrition-support/enteral-nutrition People who are unable to meet their nutritional requirements through an oral diet alone may require tube feeding; this can be delivered enterally and/or parenterally (intravenously). Enteral tube feeding is the administration of food and/or fluid via a tube into the gastrointestinal tract (see table 1).
Table 1: Indications and routes of enteral feeding2Tube type Timeframe Common indications Common Insertion methods Hazards Key interventions Common issues. Available from: https://www.bsg.org.uk/resource/bsg-guidelines-for-enteral-feeding-in-adult-hospital-patients.html
|Tube Type||Timeframe||Common Indications||Insertion Method|
|Naso-gastric tube (NGT)||Short-term (less than 30 days)||Inadequate oral intake, Acute swallowing problem, Supplementary nutrition||At bedside|
|Naso-jejunal tube (NJT)||Short-term (less than 30 days)||Gastroparesis, Recurrent vomiting or reflux, Pathology in oesophagus or stomach||Bedside magnetic imager, Endoscopy, Radiological screening|
|Gastrostomy||Long-term (more than 30 days)||Neurological disease or brain injury, Oesophageal pathology: head and neck cancer||Endoscopy, Radiology, Surgery|
|Jejunostomy||Long-term (more than 30 days)||Long-term: i.e. Gastroparesis, Recurrent vomiting or reflux, Pathology in the oesophagus or stomach||Endoscopy (direct), Endoscopy, (extension via gastrostomy), Radiology (transgastric), Surgery|
Gastrointestinal challenges of enteral nutrition
Gastrointestinal complications related to EN include altered gut transit time, vomiting, constipation and diarrhoea. These symptoms can disrupt the diversity of gut microbiota (a community of microorganisms found in the gut). Altered microbial diversity is a marker of dysbiosis, which can cause changes to the immune response and increases susceptibility towards disease.3 Malik AA, Rajandram R, Tah PC, Hakumat-Rai VR, Chin KF. Microbial cell preparation in enteral feeding in critically ill patients: A randomized, double-blind, placebo-controlled clinical trial. Journal of Critical Care. 2016 Apr 1;32:182–8,4Tatsumi H. Enteral tolerance in critically ill patients. Vol. 7, Journal of Intensive Care. BioMed Central Ltd.; 2019. Available from: https://europepmc.org/article/pmc/pmc6505301,5Valdes AM, Walter J, Segal E, Spector TD. Role of the gut microbiota in nutrition and health. BMJ (Online) [Internet]. 2018 Jun 13;361:36–44. Available from: http://www.bmj.com/ Recent research has explored the impact of modulation of the gut microbiome on enteral tolerance in tube fed hospital patients.4Tatsumi H. Enteral tolerance in critically ill patients. Vol. 7, Journal of Intensive Care. BioMed Central Ltd.; 2019. Available from: https://europepmc.org/article/pmc/pmc6505301
Probiotics and prebiotics in enteral nutrition
Probiotics, prebiotics and synbiotics (see table 2 for definitions) are sometimes used in patients receiving long-term enteral tube feeds, particularly in those who are critically ill or have EN-associated diarrhoea. This section will explore the current evidence base for the use of probiotics, prebiotics and synbiotics in the management of patients receiving enteral tube feeding.
Table 2: Definitions of probiotics, prebiotics and synbiotics
|Probiotics||Live microorganisms which when administered in adequate amounts confer a health benefit on the host.6FAO/WHO. Guidelines for the evaluation of probiotics in food. Food and Agriculture Organization of the United Nations and World Health Organization Group Report.(London Ontario, Canada). FAO Food and Nutrition Paper 85. 2002.|
|Prebiotics||Ingredients selectively used by host microorganisms that confer a health benefit.6FAO/WHO. Guidelines for the evaluation of probiotics in food. Food and Agriculture Organization of the United Nations and World Health Organization Group Report.(London Ontario, Canada). FAO Food and Nutrition Paper 85. 2002. Dietary sources of prebiotics include onions, leeks, celery, legumes and oats.7Cresci GAM, Lampe JW, Gibson G. Targeted Approaches for In Situ Gut Microbiome Manipulation. Journal of Parenteral and Enteral Nutrition. 2020. 44(4):581–8. Available here|
|Synbiotics||A dietary supplement containing a combination of probiotics and prebiotics, which together, confer a health benefit.6FAO/WHO. Guidelines for the evaluation of probiotics in food. Food and Agriculture Organization of the United Nations and World Health Organization Group Report.(London Ontario, Canada). FAO Food and Nutrition Paper 85. 2002.|
EN-associated diarrhoea can be caused by a variety of factors such as antibiotic use, medications, lactose intolerance and enteral feed composition (i.e. the presence or absence of dietary fiber or the osmolarity of the feed).4Tatsumi H. Enteral tolerance in critically ill patients. Vol. 7, Journal of Intensive Care. BioMed Central Ltd.; 2019. Available from: https://europepmc.org/article/pmc/pmc6505301 Prolonged diarrhoea can impair nutrient absorption, which can lead to malnutrition and increased risk of mortality.8Wiesen P, van Gossum A, Preiser JC. Diarrhoea in the critically ill [Internet]. Vol. 12, Current Opinion in Critical Care. Curr Opin Crit Care; 2006. p. 149–54. Available from: https://pubmed.ncbi.nlm.nih.gov/16543792/ Thus, the use of prebiotics and probiotics have been explored as a method of managing EN-associated diarrhoea.
Randomised controlled trials of probiotics and their effects on EN-associated diarrhoea have reported inconsistent findings. However, Saccharomyces boulardii has been shown to reduce the incidence of diarrhoea in adult patients receiving EN on the intensive care unit.9Whelan K. Enteral-tube-feeding diarrhoea: Manipulating the colonic microbiota with probiotics and prebiotics – BAPEN Symposium 2 on “Pre- and probiotics.” In: Proceedings of the Nutrition Society. 2007. Further research is required to examine the efficacy of probiotics and prebiotics in the prevention of EN-associated diarrhoea before it can be considered an efficacious treatment.
Clostridium difficile-associated diarrhoea
Changes to gut microbiota as a result of EN or antibiotic use can lead to increased susceptibility to infectious pathogens such as Clostridium difficile. A Cochrane review of thirty‐nine studies (n= 9,955) found that in patients receiving antibiotic therapy, probiotics reduced the risk of clostridium difficile-associated diarrhoea (CDAD) by 60%.10Goldenberg JZ, Yap C, Lytvyn L, Lo CKF, Beardsley J, Mertz D, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Vol. 2017, Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd; 2017. Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006095.pub4/full
Probiotic administration also reduced the incidence of CDAD-related symptoms (including abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance) in 17% of participants. Based on this systematic review, it can be concluded that probiotics are effective for the management of CDAD. However, it is important to note that these participants were not receiving enteral nutrition; further research is required to examine the role of probiotics and management of CDAD in enterally tube fed patients.
Prevention of sepsis in critically ill patients
A systematic review in 2018 examined data from 32 trials to assess the effects of probiotic-enriched EN formulas on clinical outcomes in critically ill patients. Probiotic-enriched EN formulas did not affect hospital or intensive care unit (ICU) mortality rates. The addition of Lactobacillus plantarum was associated with a significant reduction in overall infection rates, however this was only seen in a subgroup of lower-quality studies. Probiotic-enriched EN formulas had no effect on length of hospital admission, although it may have contributed to a shortened ICU admission.11Nutrition CC. Enteral Nutrition: Probiotics. 2018; Available from: https://www.criticalcarenutrition.com/docs/systematic_reviews_2018/6.2%20Probiotics_2018.pdf
A further study randomised 65 critically ill trauma patients to receive an enteral formula supplemented with four probiotics (Pediococcus pentosaceus, Leuconostoc mesenteroides, L. paracasei and L. plantarum) and prebiotics (inulin, oat bran, pectin, and resistant starch) or a placebo. Synbiotic-treated patients showed a significantly reduced rate of infections, sepsis severity, and mortality. This subsequently reduced the duration of ventilatory support and intensive care admission.12Kotzampassi K, Giamarellos-Bourboulis EJ, Voudouris A, Kazamias P, Eleftheriadis E. Benefits of a synbiotic formula (Synbiotic 2000Forte®) in critically ill trauma patients: Early results of a randomized controlled trial. World Journal of Surgery. 2006 Oct. 30(10):1848–55. Available from: https://pubmed.ncbi.nlm.nih.gov/16983476/
Probiotics are considered to be safe in healthy populations; however a cautious approach is required for specific patient groups. For example, probiotic supplementation in the critically ill may result in bacterial translocation, whereby bacteria from the GI tract enters extraintestinal sites which can lead to sepsis.13Whelan K, Myers CE. Safety of probiotics in patients receiving nutritional support: a systematic review of case reports, randomized controlled trials, and nonrandomized trials. The American Journal of Clinical Nutrition.2010.91(3):687–703. Available from: https://academic.oup.com/ajcn/article/91/3/687/4597201 Additionally, the use of probiotic supplementation may be contraindicated in those with acute pancreatitis, people who are immunocompromised or in patients post-transplantation.14Arvanitakis M, Ockenga J, Bezmarevic M, Gianotti L, Krznari C E Z, Lobo DN, et al. ESPEN Guideline ESPEN guideline on clinical nutrition in acute and chronic pancreatitis. 2020. Available from: https://doi.org/10.1016/j.clnu.2020.01.004,15Doron, Shira, and David R Snydman. “Risk and safety of probiotics.” Clinical infectious diseases : an official publication of the Infectious Diseases Society of America vol. 60 Suppl 2,Suppl 2. 2015: S129-34. doi:10.1093/cid/civ085 Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490230/
Further research is required to determine the clinical benefits of microbiome modulation in patients receiving enteral tube feeds. The American Society of Parenteral and Enteral Nutrition (ASPEN) cannot make recommendations at present for the routine use of probiotics across the general population of ICU patients. They suggest that probiotics may be used where there is documented safety and outcome benefit, for example in EN-associated diarrhoea.16American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM).2016. Available from: https://journals.sagepub.com/page/pen/podcasts
To minimise adverse clinical outcomes, a risk-benefit analysis and routine monitoring should be undertaken when considering probiotic and prebiotic supplementation in specific patient groups, including those who are immunocompromised or critically ill.