Alcohol, GI cancer and microbiota
To what extent might alcohol consumption drive or modify the relationship between gut microbiota and GI cancer?
In the ‘European Code Against Cancer', the International Agency for Research on Cancer (IARC) identify 12 ways to reduce the risk of developing cancer, one of which has to do with alcohol consumption.1 Indeed, the Code advises “If you drink alcohol of any type, limit your intake. Not drinking alcohol is better for cancer prevention.” This recommendation is perhaps not surprising given that alcohol has been identified as a cause of at least seven types of cancer, most of which are gastrointestinal (i.e. cancer of the mouth, pharynx, oesophagus, liver, colon and rectum).1Working with clinical microbiology and microbiome analysis on a daily basis, I’m interested in the use of gut microbiota profiling for predicting human health and disease, including relationships between microbes and cancer. Dysbiosis and predominance of particular gut microbiota communities are thought to be involved in the development of, for example, colorectal cancer (CRC).2–4 But to what extent might alcohol consumption drive or modify such relationships? There may be several answers to this question, and, as exemplified by a recent study, they may not be black and white…5 In their study, Tsuruya et al. investigated the ecophysiological consequences of alcoholism on human gut microbiota.5 Detailing and corroborating the findings of others,6 they found that the gut microbiota of alcoholics were depleted in dominant obligate anaerobes (e.g. Ruminococcus) and enriched in aerotolerant (facultative anaerobic) groups, including Streptococcus and other minor species. That the distribution is skewed towards facultative anaerobes in alcoholics reflects—at least in part—the influence of oxidative stress due to ethanol-induced formation of reactive oxygen species by, for example, gut mucosal cells. The team go on to explain how the different major groups of bacteria metabolize ethanol under different ecological circumstances, which includes the production of acetaldehyde (the carcinogenic metabolite derived from alcohol that is thought to be critical to the development of ethanol-related CRC). While I strongly encourage you to acknowledge the complexity of these intricate relationships, what I find particularly intriguing is the extent to which it is possible to predict gut ecology (e.g. the level of oxidative stress) by microbiota profiling, since this could impact the way we manage and prevent cancers such as CRC. Strong epidemiological data suggest there is a dose–response relationship between alcohol consumption and the risk of CRC.7–10 And when it comes to alcohol (ab)use and the risk of developing and dying from CRC, it might be useful to look not only at the gut bacteria that are present and what they do, but also at those bacteria that are absent. For instance, the diet of individuals who consume excessive amounts of alcohol might favour gut microbiota changes that increase susceptibility to cancer development. Some bacteria produce short-chain fatty acids (SCFAs), which are most likely protective against the development of CRC.4,11 Such bacteria are established in the gut typically in relation to a diet rich in fibre. If the overall diet of alcoholics promotes (e.g. via malnutrition) a reduction in bacteria producing SCFAs, this could indirectly lead to an increased CRC risk. The possible opportunities here are manifold, but I will end by mentioning what I consider the two most important ones. First, microbiota profiling can be used as a noninvasive diagnostic/prognostic marker for various aspects of health and disease; stool analysis might in the future enable us to tell if a patient is an alcoholic, what type of food they eat (if you include profiling of eukaryotic cells in stool as well), and what the likelihood of, for example, CRC is in this patient. Second, microbiota manipulation—through diet, antibiotics, or gut microbiota transplantation—may be used with a view to reducing morbidity and mortality from cancer, not only CRC, but possibly also other types of cancer. References
- International Agency for Research on Cancer. European Code Against Cancer (https://cancer-code-europe.iarc.fr/index.php/en/) [accessed March 21, 2017].
- Gagnière J, Raisch J, Veziant J, et al. Gut microbiota imbalance and colorectal cancer. World J Gastroenterol 2016; 22: 501–518.
- Dulal S and Keku TO. Gut microbiome and colorectal adenomas. Cancer J 2014; 20: 225–231.
- Vipperla K and O’Keefe SJ. Diet, microbiota, and dysbiosis: a ‘recipe’ for colorectal cancer. Food Funct 2016; 7: 1731–1740.
- Tsuruya A, Kuwahara A, Saito Y, et al. Ecophysiological consequences of alcoholism on human gut microbiota: implications for ethanol-related pathogenesis of colon cancer. Sci Rep 2016; 6: 27923.
- Mutlu EA, Gillevet PM, Rangwala H, et al. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol 2012; 302: G966–978.
- Bailie L, Loughrey MB and Coleman HG. Lifestyle risk factors for serrated colorectal polyps: a systematic review and meta-analysis. Gastroenterology 2017; 152: 92–104.
- Wang YM, Zhou QY, Zhu JZ, et al. Systematic review with meta-analyses: alcohol consumption and risk of colorectal serrated polyp. Dig Dis Sci 2015; 60: 1889–1902.
- Bagnardi V, Rota M, Botteri E, et al. Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer 2015; 112: 580–593.
- Cai S, Li Y, Ding Y, et al. Alcohol drinking and the risk of colorectal cancer death: a meta-analysis. Eur J Cancer Prev 2014; 23: 532-539.
- Bultman SJ. Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer. Mol Nutr Food Res 2017; 61.
ESGAR & EPC Pancreas workshop
This multidisciplinary course takes place on September 21 - 22, 2017 in Stockholm – register now!
Mistakes in the use of PPIs and how to avoid them
PPIs are frequently prescribed—being knowledgeable about them is fundamental.
Proton pump inhibitors (PPIs) inhibit gastric acid secretion by blocking the gastric hydrogen potassium ATPase (H-K-ATPase). When omeprazole, the first PPI, became available in 1988, it soon appeared to be more effective than H2 antagonists, and PPIs rapidly became one of the most prescribed drug classes worldwide.1PPIs have proven highly efficient for the management of gastro-oesophageal reflux disease (GORD), gastroduodenal ulcers and in the treatment of Helicobacter pylori infections. PPIs are, however, also commonly prescribed for chronic complaints of dyspepsia and upper abdominal discomfort, for which there is no proof that gastric acid is an underlying pathophysiological factor. Lately, the safety of long-term PPI use has been the subject of debate, because chronic use of PPIs has been linked to several complications, such as vitamin and mineral malabsorption, pneumonia, gastrointestinal infections and dementia.2 For anyone working in gastroenterology, having knowledge of one of the most prescribed drugs in this field is fundamental. As such, we address nine frequently made mistakes when it comes to the use of PPIs, and also hope to disprove some of the misconceptions about PPI use.
Mistakes in alcoholic liver disease and how to avoid them
ALD is multifaceted—its management poses many difficulties and pitfalls.
Alcohol consumption is the most prevalent aetiology for liver cirrhosis in Europe and the third leading risk factor for overall mortality.1,2 In fact, alcoholic liver cirrhosis accounts for almost half a million deaths a year worldwide, corresponding to 50% of all cases of cirrhosis, according to the World Health Organization (WHO).3 Alcoholic liver disease (ALD) is multifaceted, with several cofactors influencing its progression. Patients abusing alcohol can simultaneously have viral hepatitis B or C, or a genetic disease, such as alpha-1 antitrypsin deficiency or haemochromatosis.Alcohol consumption is usually assessed in pure grams per day and has a direct relationship with liver damage. Daily alcohol consumption of >30 g for men and >20 g for women is considered the cut-off volume at which there is a risk of developing alcohol-related liver disease.4 Besides volume, the pattern of consumption is also a significant factor, with heavy episodic drinking (HED) defined as an intake of 60 g or more of pure alcohol on at least one occasion in the past 30 days. Regarding HED, there is scarce information on the threshold to be applied to this pattern of drinking.5 Although the relationship between alcohol consumption and ALD is well defined, it must be acknowledged that severe disease only develops in a fraction of those who consume excessive amounts of alcohol. Nonetheless, the disease course is very much influenced by the pattern of drinking, with periods of abstinence or heavy drinking clearly altering its progression.5 ALD can present in different stages, ranging from steatosis to more severe disease, such as the clinical syndrome of alcoholic hepatitis, or decompensated liver cirrhosis, which is sometimes complicated by liver cancer. In the setting of alcoholic hepatitis, several scores, such as the Maddrey discriminant function, Glasgow alcoholic hepatitis score (GASH) and ABIC, may be used to evaluate disease severity, predict short-term survival, and decide on the need for specific treatment. Later on, the Lille score, which includes the reduction in serum bilirubin levels at day 7, evaluates the response to prednisolone after one week, in order to decide whether to continue or stop treatment.5 Despite being a frequent disease, the different aspects of ALD mean that its management still poses many difficulties and pitfalls. In this article we discuss frequent mistakes in ALD, based on the current guidelines and some paradigmatic real-life cases.
Mistakes in EoE and how to avoid them
EoE is the second-most frequent cause of chronic oesophagitis.
Eosinophilic oesophagitis (EoE) is a chronic immune-mediated inflammatory condition that is confined to the oesophagus. Clinically, EoE is characterized by symptoms of oesophageal dysfunction; histologically, by eosinophil-predominant inflammation.1,2 At present, EoE is the second-most frequent cause of chronic oesophagitis (gastro-oesophageal reflux disease [GORD] is the primary cause) and the foremost cause of dysphagia and food impaction in young adults and children.The first descriptions of EoE date back to the early 1990s,3,4 but at that time the condition was largely underappreciated and treated as GORD. Recognition of EoE grew with the rapid increase of paediatric and adult patients diagnosed since 2003, but so did confusion surrounding diagnostic criteria and treatment. The first consensus guidelines for the diagnosis and management of EoE were published in 2007 and were instrumental in bringing EoE to light as a distinct new condition.5 Since 2007, the diagnostic criteria for EoE have constantly and rapidly changed. New evidence for therapeutic agents has mounted, especially during the past 5 years. Here, we discuss the critical pitfalls that frequently occur in daily practice when dealing with EoE patients. The discussion is evidence based and in line with the recommendations included in the updated guidelines for diagnosis and management of EoE in children and adults.6
Mistakes in liver function test abnormalities and how to avoid them
Liver function tests (LFTs) are routinely used to screen for liver disease, but the assessment of LFTs can be challenging. The LFT itself must be clearly understood and the results interpreted in light of the specific clinical setting.
Liver function tests (LFTs) are routinely used to screen for liver disease. A correct interpretation of LFT abnormalities may suggest the cause, severity, and prognosis of an underlying disease. Once the diagnosis has been established, sequential LFT assessment can be used to assess treatment efficacy.Abnormal LFTs are frequently encountered in clinical practice, since elevation of at least one LFT occurs in more than 20% of the population.1 Many patients with abnormal LFTs, however, do not suffer from structural liver disease, since these tests can be influenced by factors unrelated to significant liver damage or liver function loss. During normal pregnancy, for example, serum albumin levels fall due to plasma volume expansion, and alkaline phosphatase (ALP) levels rise due to placental influx. Patients who have elevated transaminase levels may not suffer from liver disease, but rather from cardiac or skeletal muscle damage. Conversely, patients who suffer from advanced liver disease, such as chronic hepatitis or compensated liver cirrhosis, may have normal LFTs.
In short, the assessment of LFTs can represent a challenge for physicians. The observations above demonstrate the need for a firm understanding of the individual LFT, and the ability to interpret the results in the light of a specific clinical setting. Such an understanding is not merely a goal on its own, but may serve as a template to avoid mistakes in interpreting LFT abnormalities. In the following sections, we discuss several mistakes frequently made in the interpretation of LFTs and how to avoid them. Most of the discussion is evidence based, but where evidence is lacking the discussion is based on extensive clinical experience.
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Mistakes in managing perianal disease and how to avoid them
Perianal disease is very common and can impair quality of life significantly. It is crucial to identify the serious causes of these symptoms, but also to reduce the burden of the less dangerous conditions that nevertheless can be debilitating and interfere with an individual’s work and life.
Perianal disease takes many forms, is very common and can impair quality of life significantly. The symptoms of perianal disease, including pain, bleeding, discharge and pruritus, are common to several conditions that are sometimes difficult to disentangle.
It is crucial to identify the serious causes of perianal symptoms, but also to reduce the burden of the less dangerous conditions that nevertheless can be debilitating and interfere with an individual’s work, social or intimate life. Below we discuss some of the frequent and important mistakes made in the management of perianal disease based, where possible, on evidence, and where not, on clinical experience.
A case of colitis
An unusual presentation of a common problem or a common presentation of an unusual problem?
A 65-year-old man presents with a 1-week history of increasingly intense and continuous low abdominal pain that does not appear to be exacerbated by eating. The abdominal pain was preceded by exertional chest pain that settled with anti-anginal therapy prescribed by the patient’s GP. Routine blood tests are normal on admission and the patient denies taking an NSAID or paracetamol.An abdominal CT (image A) is organised followed by a colonoscopy. The colonoscopy detects the presence of ulceration (image B) at the caecum and proximal ascending colon, but the appearance is normal elsewhere. Mucosal samples are taken. Apart from hypertension that is managed with ramipril, the recently started anti-anginal drug nicorandil and low-dose aspirin, the patient is well and able walk several miles without shortness of breath. Unfortunately, the patient deteriorates a couple of days later and becomes septic. A repeat abdominal CT confirms the presence of a perforation at the level of the caecum, and the patient undergoes an emergency hemi-colectomy. Analysis of the resection specimen confirms deep ulceration with a perforation at the centre of an area of ulceration (image C). WHAT IS THE MOST LIKELY DIAGNOSIS? a) Ischaemic colitis b) Aspirin-induced colonic ulceration c) Ulceration secondary to mucosal biopsy samples taken at colonoscopy d) Crohn’s disease e) None of the above
Mistakes in endoscopy and how to avoid them
Diagnostic and therapeutic mistakes discussed in the context of evidence and endoscopic experience.
Upper and lower gastrointestinal endoscopy examinations are performed daily as routine diagnostic procedures in a large number of patients with nonspecific indications, such as heartburn, pain, anaemia, bleeding, workup of portal hypertension and so on.Most of the examinations will point to a classic diagnosis (e.g. peptic disease, cancer, variceal management), but sometimes we see patients who've had multiple diagnostic endoscopic procedures in the previous few months with nonconclusive findings. The diagnostic mistakes discussed here are those that sprang to mind based on our endoscopic experience and they are discussed in an evidence-based approach. For therapeutic endoscopic procedures (e.g. ERCP and resections), we present the most important mistakes that are often seen in our practice and have major consequences for the patient. We propose, from our experience, a simple approach to avoid these mistakes.
All UEG Week 2016 content is included in the UEG Education Library
In addition to the recordings on UEG Week 24/7, the scientific material of UEG Week 2016 is available in the UEG Education library, including all abstracts, posters and the syllabus of the Postgraduate Teaching Programme.
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Mistakes in paediatric functional constipation diagnosis and treatment and how to avoid them
Have a look at the major mistakes that are made when diagnosing and treating children with functional constipation.
Constipation is a bothersome problem for many children. It may present as one or more of the following: infrequent bowel movements with faecal incontinence, hard and often large stools, painful defecation and abdominal pain. No organic cause of the constipation can be found in approximately 95% of children—these children suffer from functional constipation. The prevalence of functional constipation ranges between 0.7% and 29.6% and it occurs in girls more often than in boys (ratio 2.1:1).1The diagnosis of functional constipation is based on the paediatric diagnostic Rome criteria for functional gastrointestinal disorders.2,3 Additional investigations are indicated only if the diagnosis is not clear or in order to rule out an underlying organic disease, such as Hirschsprung disease.4 Education, demystification of constipation, following a reward-based toilet program and keeping a daily bowel diary form part of the nonpharmacological management process.4 Disimpaction, maintenance treatment and weaning of medication are all elements of pharmacological treatment.4 Polyethylene glycol (PEG) is the first-choice laxative for both disimpaction and maintenance treatment; however, if PEG is not available or is poorly tolerated, lactulose is recommended. Other laxatives are available as a second-line or additional treatment if treatment with PEG is insufficient. Here we discuss the major mistakes that are made when diagnosing and treating children with functional constipation. The discussion that follows is evidence based in the majority of cases, but where evidence is lacking the discussion is based on the lead author’s clinical experience of more than 20 years in the field as a paediatric gastroenterologist.
Mistakes in irritable bowel syndrome and how to avoid them
Learn more about the mistakes that can be made when diagnosing and managing IBS!
Around 11% of the worldwide population experience irritable bowel syndrome (IBS), making it one of the most frequent gastroenterological diagnoses.1 The symptoms of IBS include abdominal pain associated with unpredictable bowel habits and variable changes in the form and frequency of stool.2While all patients with IBS suffer from recurrent bouts of abdominal pain, their bowel habits are varied: around one-third suffer predominantly with diarrhoea (IBS-D), one-fifth experience predominantly constipation (IBS-C) and half have an erratic mixed pattern of both diarrhoea and constipation (IBS-M).3 This very heterogeneous condition undoubtedly has multiple causes and an individualized approach to management and treatment is required. Here I discuss the mistakes most frequently made when diagnosing and managing IBS. The mistakes and discussion that follow are based, where possible, on published data and failing that on many years of my own clinical experience.
Clinical Introduction to colorectal polyps
Improve your understanding of colorectal polyps.
Learn more about importance of the gut microbiota in many clinical conditions.
Emergency upper gastrointestinal bleeding
Enhance your knowledge of nonvariceal and variceal bleeding.
Mistakes in the management of acute pancreatitis and how to avoid them
Critical decision-making points & pitfalls
Acute pancreatitis is a common inflammatory disorder of the pancreas and its incidence is increasing among hospitalized patients worldwide.
The main symptoms include severe upper abdominal pain (often sudden onset), nausea, vomiting, bloating and the development of ileus. In many cases jaundice will also be present. The diagnosis, as agreed by international consensus, can be established by fulfilling two of the following three criteria: upper abdominal pain of sudden onset, elevation of either serum lipase or amylase activity to greater than three times the upper limit of normal, and imaging findings consistent with inflammation of the pancreas.4–6
By far the most common risk factors for the development of acute pancreatitis are excessive alcohol consumption and gallstone disease. Several mutations have been identified that, in combination with nongenetic factors or alone, can lead to pancreatitis. Certain drugs are known to be associated with the development of pancreatitis and smoking might also increase the probability of it developing. 80–85% of patients diagnosed with the disease will have mild disease and make an uneventful recovery with little more than adequate fluid therapy and analgesia needed to support them. The remaining patients, however, will suffer from moderately severe to severe acute pancreatitis, with the development of pancreatic necrosis, severe sepsis or abdominal compartment syndrome. These patients are at immediate danger of multiorgan failure and death and require multidisciplinary intensive care, organ support and often pancreatic interventions conducted by experienced investigators. Since it is difficult to predict outcomes and complications develop during the disease course, treatment in specialized centres that have a high case load is recommended.4
Here, we discuss critical decision-making points and pitfalls frequently occurring when managing patients with acute pancreatitis. The discussion is based on the medical literature and many years of clinical experience.
In 2009, it was the most frequent diagnosis in patients discharged from GI services in the US and the fifth leading cause of in-hospital mortality.1 Because of this high disease burden, acute pancreatitis is also a substantial contributor to healthcare spending, accounting for an estimated annual spend of US$4–7 million per million inhabitants in western countries.2,3
NAFLD and diabetes—are they symptoms of gut dysbiosis?
Connecting changes in gut microbiota to metabolic and hepatic diseases
The idea that obesity is a direct consequence of changes in gut microbiota structure and function that lead to enhanced extraction of energy from the host diet has been discussed for some years. Studies now suggest that associated diseases such as non-alcoholic fatty liver disease (NAFLD) and diabetes may also be considered consequences of intestinal dysbiosis.A leading cause of liver transplantation, NAFLD may now top the list of the most common liver diseases in developed countries. In an article published in Gastroenterology earlier this year, Betrapally and colleagues argue that “…the development and progression of fatty liver, alcoholic fatty liver disease, and NAFLD all appear to be influenced by the composition of the [gut] microbiota.”1 The way the gut microbiota influences the progression of these diseases appears to be complex, potentially involving diet-induced changes in bacterial metabolomes and microbial interactions with, for instance, bile acids and gut hormones such as glucagon-like peptide 1 (GLP1).1,2 An incretin secreted by enteroendocrine L cells, GLP1 induces pancreatic β-cell proliferation, maintains glucose-dependent insulin secretion and inhibits glucagon release, gastric emptying and food intake. Short-chain fatty acids (SCFAs) synthesized by certain bacteria activate the G-protein-coupled receptors GPR41 and GPR43, promoting secretion of GLP1.1 This was exemplified in a randomized controlled trial (RCT), in which Alisi and colleagues investigated the effect of the probiotic VSL#3, a mixture of eight probiotic strains (Streptococcus thermophilus, bifidobacteria [B. breve, B. infantis, B. longum], Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. bulgaricus) in children with NAFLD, using changes in the severity of the fatty liver disease as the primary outcome.2 They found that a 4-month supplement of VSL#3 significantly improved NAFLD, probably through VSL#3-dependent reversal of dysbiosis. Of note, however, is the fact that no data were included on gut microbiota profiling prior to or after intervention. Nevertheless, the authors speculated that restoration of normal gut flora led to reduced intestinal permeability, increased production of SCFAs and anorexogenic gut hormones, including GLP1, as well as enhanced insulin sensitivity. The effect of consuming 300g of probiotic yoghurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 every day for 8 weeks on selected metabolic parameters was studied in an RCT comprising 72 NAFLD patients.3 Patients consuming the probiotic yoghurt exhibited a reduction in the levels of serum hepatic enzymes (alanine aminotransferase and aspartate aminotransferase), serum total cholesterol, and low-density lipoprotein cholesterol. Again, no microbiota profiling was performed in order to try to link the findings with potential restoration of gut eubiosis. Meanwhile, other studies—although not intervention studies—have taken to investigating the gut microbiota profiles of patients with NAFLD lesions such as non-alcoholic steatohepatosis and fibrosis. These studies have identified independent associations between the predominance of certain bacterial groups and the presence of fatty liver disease.4,5 The fact remains, however, that we still need intervention studies that include pre-intervention and post-intervention gut microbiota profiling, preferably including data on the gut metabolome as well. And, as pointed out by Wieland and colleagues,6 we still need data in order to be able to delineate causality and obtain a mechanistic understanding of how in fact obesity and related metabolic and hepatic disease might reflect changes in gut microbiota structure and function.
We still need intervention studies that include pre-intervention and post-intervention gut microbiota profilingOn a different—yet related—note, a study has just been published in Nature identifying Prevotella copri as a driver of insulin resistance and potentially the development of type-2 diabetes.7 Mice fed P. copri developed increased serum levels of branched-chain amino acids, insulin resistance and reduced glucose tolerance. Hence, P. copri was identified as one of the bacterial species most critical to the development of insulin resistance. This finding suggests that type-2 diabetes is effectively the result of intestinal dysbiosis with predominance of certain bacteria such as P. copri. The results of future research will reveal the extent to which obesity and associated metabolic and hepatic diseases may be alleviated and perhaps even treated via gut microbiota manipulation with prebiotics, probiotics, synbiotics, antibiotics or other compounds such as SCFAs.8 If you are interested in the role of the gut microbiota in the development of NAFLD, especially changes in SCFA metabolism, I highly recommend perusing the review by Leung and colleagues in Nature Reviews Gastroenterology & Hepatology.9 For even more information on microbiota-associated pathogenesis of liver disease and its complications, I suggest reading the reviews by Schnabel and Brenner,10 Boursier and Diehl,11 Quigley and Monsour,12 and Abdou and colleagues.13 To find out more about the use of probiotics in the therapy of NAFLD, the reviews by Putignani et al.14 and Tarantino and Finelli15 are also worth consulting. References
- Betrapally NS, Gillevet PM and Bajaj JS. Changes in the intestinal microbioma and alcoholic and nonalcoholic liver diseases: Causes of effects? Gastroenterology 2016; 150: 1745–1755.
- Alisi A, Bedogni G, Beviera G, et al. Randomised clinical trial: the beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis. Aliment Pharmacol Ther 2014; 39: 1276–1285.
- Nabavi S, Rafraf M, Somi MH, et al. Effects of probiotic yogurt consumption on metabolic factors in individuals with nonalcoholic fatty liver disease. J Dairy Sci 2014; 97: 7386–7393.
- Boursier J, Mueller O, Barret M, et al. The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota. Hepatology 2016; 63: 764–775.
- 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. Sci Rep 2015; 5: 8096.
- Wieland A, Frank DN, Harnke B, et al. Systematic review: microbial dysbiosis and non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2015; 42: 1051–1063.
- Pedersen HK, Gudmundsdottir V, Nielsen HB, et al. Human gut microbes impact hos serum metabolome and insulin sensitivity. Nature 2016; 535: 376–381.
- Jin CJ, Sellmann C, Engstler AJ, et al. Supplementation of sodium butyrate protects mice from the development of non-alcoholic steatohepatitis (NASH). Br J Nutr 2015; 114: 1745–1755.
- Leung C, Rivera L, Furness JB, et al. The role of the gut microbiota in NAFLD. Nat Rev Gastroenterol Hepatol 2016; 13: 412–425.
- Schnabl B and Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 2014; 146: 1513–1524.
- Boursier J and Diehl AM. Implication of gut microbiota in nonalcoholic fatty liver disease. PLoS Pathog 2015; 11: e1004559.
- Quigley EM and Monsour HP. The gut microbiota and nonalcoholic fatty liver disease. Semin Liver Dis 2015; 35: 262–269.
- Abdou RM, Zhu L, Baker RD, et al. Gut microbiota of nonalcoholic fatty liver disease. Dig Dis Sci 2016; 61: 1268–1281.
- Putignani L, Alisi A and Nobili V. Pediatric NAFLD: the future role of patient-tailored probiotics therapy. J Pediatr Gastroenterol Nutr 2016; 63 Suppl 1: S6–8.
- Tarantino G and Finelli C. Systematic review on intervention with prebiotics/probiotics in patients with obesity-related nonalcoholic fatty liver disease. Future Microbiol 2015; 10: 889–902.