Our intestinal barrier fulfills an essential role in maintaining balance within the body, which it does by regulating the absorption of nutrients, electrolytes and water from the gastrointestinal tract into the circulation, while simultaneously preventing the entry of pathogenic microorganisms, toxic metabolites, insufficiently digested food particles, and other immune-modulatory components. Intestinal barrier function is influenced by various factors including age, diet, stress, infections, and certain medications, and any loss of barrier integrity will lead to increased permeability.1
Intestinal barrier dysfunction and increased permeability [also known as Leaky Gut] has been linked with a wide range of systemic inflammatory disorders, including various liver diseases.1-8 There is an intimate association between the gut and the liver and growing evidence indicates that the development of non-alcoholic fatty liver disease (NAFLD) is associated with the impairment of gut physical barrier function.9-12 As such, the intestinal barrier represents a target for disease prevention and treatment.
NAFLD is the most common cause of liver disease in Australia, affecting an estimated 5.5 million individuals, including 40% of all adults over the age of 50 years.13 NAFLD results from the accumulation of excess fat in the liver of people who drink little or no alcohol,14 and is an umbrella term for a range of chronic liver diseases including steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis.15 Studies assessing the association between intestinal permeability and risk of developing NAFLD and its progression into NASH, have found that patients with either of these disease states were more likely to display enhanced leaky gut.12,16
Under normal conditions, a network of tight junctions protects against bacteria moving from the gut into the systemic circulation. When tight junction integrity is impaired, intestinal permeability increases, allowing unwanted particles and substances to enter the blood stream which flows directly into the liver. Poor gut health, impaired microbiome and permeability all contribute to this influx of toxins directly to the liver. 20,22,23
The protective role of our gut microbiota in NAFLD
When everything is running smoothly, our gut microbiota maintain gut barrier function via enhanced colonisation resistance and inhibition of pathogens, enhancement of the tight junctions and modulation of the immune system. The gut microbiota also play an important role in the production of anti-inflammatory metabolites such as short-chain fatty acids (SCFAs).24 SCFAs, such as butyrate, are important for the maintenance of intestinal barrier integrity, while suppressing mucosal inflammation. Hence, SCFAs may limit hepatic damage caused by dysbiosis and microbial by-products such as LPS.23 A functional pathology or Comprehensive Stool Analysis will help identify any potential imbalances within your gut.
Bile acid secreted by the liver also plays a role in maintaining gut barrier function. Several studies point towards a dominant role of the gut microbiota in regulating bile acids which are critically involved in many of the pathways responsible for maintaining glucose and cholesterol balance. Alterations to these pathways can lead to dysregulation of energy balance and increased inflammation, which in turn contributes to obesity and its related metabolic manifestations including NAFLD.25,26
What does this mean for you?
The gut barrier is a direct physical barrier against translocation of a broad range of substances into the circulation. It is becoming more and more evident that a breakdown of gut barrier integrity plays an important role in the pathogenesis of many diseases including NAFLD. There is very little evidence that any drug is effective in treating NAFLD or slowing the disease progression of NASH, and most medical practitioners can only recommend weight loss and exercise as a treatment strategy.
This is where natural healthcare practitioners are able to help. In addition to supporting a healthy gut by ensuring integrity of the gut walls, recommending diet and lifestyle modifications and assessing your individual needs for prebiotics, probiotics and anti-inflammatory compounds a qualified naturopath can make a significant difference to the quality of your life.
You can contact True Medicine on 07 5530 1863 to arrange a consultation.
1.Fukui H. Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation? Inflammatory Intestinal Diseases. 2016;1(3):135-145.
2.Everard A, Cani PD. Diabetes, obesity and gut microbiota. Best Pract Res Clin Gastroenterol. 2013;27(1):73-83.
3.Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015;9.
4.Magistris L. Intestinal Barrier in Autism. In: Patel VB, Pretty VR, Martin CR, eds. Comprehensive Guide to Autism. New York, NY, United States: Springer-Verlag New York Inc; 2014:2047-2060.
5.Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol. 2014;20(43):16079-16094.
6.van Hemert S, Breedveld AC, Rovers JMP, et al. Migraine Associated with Gastrointestinal Disorders: Review of the Literature and Clinical Implications. Front Neurol. 2014;5.
7.Fasano A, Shea-Donohue T. Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Pract Gastroenterol Hepatol. 2005;2(9):416-422.
8.Michielan A, D’Inca R. Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut. Mediators Inflamm. 2015;2015:628157.
9.Dai X, Wang B. Role of gut barrier function in the pathogenesis of nonalcoholic Fatty liver disease. Gastroenterol Res Pract. 2015;2015:287348.
10.Oldfield EC, Dong RZ, Johnson DA. Non-alcoholic Fatty Liver Disease and the Gut Microbiota: Exploring the Connection. Gastro Open J. 2015;1(2):30-43.
11.Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009;49(6):1877-1887.
12.Llorente C, Schnabl B. The Gut Microbiota and Liver Disease. In: Cell Mol Gastroenterol Hepatol. Vol 1.2015:275-284.
13.The Gastroenterological Society of Australia. The economic cost and health burden of liver diseases in Australia. 2013; http://static1.squarespace.com/static/50ff0804e4b007d5a9abe0a5/t/53321aaee4b09f967eb0c7e5/1395792558684/gesa2013_revised%5B1%5D.pdf. Accessed 5/3/18.
14.Croke B, Sampson D. Nonalcoholic Fatty Liver Disease: Implications for Clinical Practice and Health Promotion. The Journal for Nurse Practitioners. 2012;8(1):45-50.
15.Banini BA, Sanyal AJ. Nonalcoholic Fatty Liver Disease: Epidemiology, Pathogenesis, Natural History, Diagnosis, and Current Treatment Options. Clin Med Insights Ther. 2016;8:75-84.
16.Luther J, Garber JJ, Khalili H, et al. Hepatic Injury in Nonalcoholic Steatohepatitis Contributes to Altered Intestinal Permeability. Cell Mol Gastroenterol Hepatol. 2015;1(2):222-232.
17.Jiang W, Wu N, Wang X, et al. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Scientific Reports. 2015;5:8096.
18.Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas M-E. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Medicine. 2016;8(1):42.
19.Xue L, He J, Gao N, et al. Probiotics may delay the progression of nonalcoholic fatty liver disease by restoring the gut microbiota structure and improving intestinal endotoxemia. Scientific Reports. 2017;7:45176.
20.Zhu L, Baker RD, Baker SS. Gut microbiome and nonalcoholic fatty liver diseases. Pediatr Res. 2015;77(1-2):245-251.
21.Baker SS, Baker RD, Liu W, Nowak NJ, Zhu L. Role of alcohol metabolism in non-alcoholic steatohepatitis. PLoS One. 2010;5(3):e9570.
22.Bajaj JS. The Relationship Between the Gut Microbiota and Liver Disease. Gastroenterol Hepatol (N Y). 2015;11(9):626-628.
23.Bashiardes S, Shapiro H, Rozin S, Shibolet O, Elinav E. Non-alcoholic fatty liver and the gut microbiota. In: Mol Metab. Vol 5.2016:782-794.
24.Schwiertz A, Taras D, Schafer K, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190-195.
25.Yuan L, Bambha K. Bile acid receptors and nonalcoholic fatty liver disease. World J Hepatol. 2015;7(28):2811-2818.
26.Chow MD, Lee Y-H, Guo GL. The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Molecular Aspects of Medicine. 2017;56:34-44.