Role of the Gut–Liver Axis in Driving Parenteral Nutrition-Associated Injury
Abstract
:1. Introduction
2. Evidence Supporting the Importance of Enteral Nutrition and Luminal Content
2.1. Hepatic Injury
2.2. Gut Injury
3. Gut–Liver Axis
3.1. Portal System
3.2. Gut Microbiota
3.2.1. Human Gut Microbiota
3.2.2. TPN and Modulation of Gut Microbiota
3.3. Hepatobiliary Receptors and Transporters
3.3.1. FXR-FGF19 Axis
3.3.2. TGR5–GLP Axis
3.4. GLP-2 and EGF
4. Expert Commentary: Five-Year View and Conclusion
5. Key Issues
- Parenteral nutrition (PN) has been a successful method for the intravenous delivery of nutrients and remains an essential therapy for individuals with intolerance of enteral feedings or impaired gut function. PN provides nourishment via the intravenous administration of nutritional components, such as amino acids, glucose, vitamins, minerals, and lipids. When nutritional needs are solely met via such intravenous therapy, the resulting process is called total parenteral nutrition (TPN).
- TPN remains an essential modality of nutrition delivery worldwide and is commonly used in neonates and pediatric and adult patients with lost or impaired gut function. TPN use has grown exponentially over the last few decades.
- Despite the several benefits of TPN therapy, its use is associated with adverse effects. Parenteral nutrition-associated liver disease (PNALD) is a cholestatic liver disease, which can also present with hepatic inflammation, steatosis, dyslipidemia, glucose intolerance, and/or fibrosis. Significant gut mucosal atrophy has also been shown to occur in association with TPN infusion in several animal studies.
- The pathophysiology and etiology of TPN-associated injury remains largely unknown despite several theories.
- Research into ameliorative therapies and mechanistic pathways continues to be a major focus in the field of gastroenterology and hepatology.
- Recent studies reveal that an alteration in gut-derived signals may occur with administration of TPN in the absence of enteral nutrition. This hypothesis is driven by the observation that hepatic injury is decreased if even a small percentage of nutrition can be provided enterally.
- Based on the concept that gut-derived signals, stimulated by intraluminal nutrients, can maintain liver health, it is hypothesized that in the state of TPN, the enterohepatic axis is disrupted, thus leading to injury.
- Current data, including work from our lab, support the theory that altered gut–liver crosstalk with TPN and bile acids have emerged as key regulators of injury. In fact, treatment with bile acid receptor agonists seems to ameliorate TPN-associated injury in animal models.
- Translating research from bench to clinical targeting of the gut-derived signaling appears to be key in developing novel approaches in mitigating TPN-associated injury and restoring the effectiveness of this lifesaving therapy.
Author Contributions
Funding
Conflicts of Interest
References
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Denton, C.; Price, A.; Friend, J.; Manithody, C.; Blomenkamp, K.; Westrich, M.; Kakarla, V.; Phillips, W.; Krebs, J.; Munoz Abraham, A.S.; et al. Role of the Gut–Liver Axis in Driving Parenteral Nutrition-Associated Injury. Children 2018, 5, 136. https://doi.org/10.3390/children5100136
Denton C, Price A, Friend J, Manithody C, Blomenkamp K, Westrich M, Kakarla V, Phillips W, Krebs J, Munoz Abraham AS, et al. Role of the Gut–Liver Axis in Driving Parenteral Nutrition-Associated Injury. Children. 2018; 5(10):136. https://doi.org/10.3390/children5100136
Chicago/Turabian StyleDenton, Christine, Amber Price, Julie Friend, Chandrashekhara Manithody, Keith Blomenkamp, Matthew Westrich, Vindhya Kakarla, William Phillips, Joseph Krebs, Armando Salim Munoz Abraham, and et al. 2018. "Role of the Gut–Liver Axis in Driving Parenteral Nutrition-Associated Injury" Children 5, no. 10: 136. https://doi.org/10.3390/children5100136