Alimentary Pharmacology and Therapeutics

Background  Non‐alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, and its worldwide prevalence continues to increase with the growing obesity epidemic. This study assesses the epidemiology of NAFLD in adults based on clinical literature published over the past 30 years.

Aim  To review epidemiology and natural history of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in adults based on clinical literature published over the past 30 years.

Methods  An in‐depth search of PubMed (1980–2010) was based on five search terms: ‘non‐alcoholic fatty liver disease’ OR ‘non‐alcoholic steatohepatitis’ OR ‘fatty liver’ OR ‘steatosis’ AND ‘incidence’ [MeSH Terms] OR ‘prevalence’ [MeSH Terms] OR ‘natural history’. Studies of paediatric cohorts were excluded. Articles were categorised by topic and summarised, noting generalisations concerning their content.

Results  Four study categories included NAFLD incidence, prevalence, risk factors and natural history. Studies related to NAFLD prevalence and incidence indicate that the diagnosis is heterogeneous and relies on a variety of assessment tools, including liver biopsy, radiological tests such as ultrasonography, and blood testing such as liver enzymes. The prevalence of NAFLD is highest in populations with pre‐existing metabolic conditions such as obesity and type II diabetes. Many studies investigating the natural history of NAFLD verify the progression from NASH to advanced fibrosis and hepatocellular carcinoma.

Conclusions  Non‐alcoholic fatty liver disease is the most common cause of elevated liver enzymes. Within the NAFLD spectrum, only NASH progresses to cirrhosis and hepatocellular carcinoma. With the growing epidemic of obesity, the prevalence and impact of NAFLD continues to increase, making NASH potentially the most common cause of advanced liver disease in coming decades.

: Although 5‐aminosalicylic acid (5‐ASA) oral compounds are the standard maintenance treatment for ulcerative colitis in remission, some patients cannot use them because of side‐effects. Clinical and experimental observations have suggested the potential role of probiotics in inflammatory bowel disease therapy.

: To evaluate the effects on intestinal microflora and the clinical efficacy of a new probiotic preparation in patients with ulcerative colitis in remission.

: Twenty patients with ulcerative colitis, intolerant or allergic to 5‐ASA, have been treated with a new probiotic preparation (VSL # 3, CSL, Milan, Italy) containing 5 × 10¹¹ cells/g of 3 strains of bifidobacteria, 4 strains of lactobacilli and 1 strain of Streptococcus salivarius ssp. thermophilus. Two doses of 3 g were administered o.d. for 12 months. Faecal samples for stool culture were obtained from the patients at the beginning of the trial and after 10, 20, 40, 60, 75, 90 days, 12 months and at 15 days after the end of the treatment. The following bacterial groups have been evaluated in the faeces: total aerobic and anaerobic bacteria, enterococci, Streptococcus thermophilus, lactobacilli, bifidobacteria, Bacteroides, clostridia, coliforms. Patients were assessed clinically every two months, and assessed endoscopically at 6 and 12 months or in relapse.

: Faecal concentrations of Streptococcus salivarius ssp. thermophilus, lactobacilli and bifidobacteria increased significantly in all patients, compared to their basal level, from the 20th day of treatment (P < 0.05) and remained stable throughout the study. Concentrations of Bacteroides, clostridia, coliforms, total aerobic and anaerobic bacteria did not change significantly during treatment (P = N.S.). Fifteen of 20 treated patients remained in remission during the study, one patient was lost to follow up, while the remaining relapsed. No significant side‐effects have been reported.

: These results show that this probiotic preparation is able to colonize the intestine, and suggest that it may be useful in maintaining the remission in ulcerative colitis patients intolerant or allergic to 5‐ASA. Controlled trials are warranted to confirm these preliminary results.

Irritable bowel syndrome (IBS) is a chronic functional bowel disorder. Disturbances in the gastrointestinal microbiome may be involved in its aetiology.

To perform a systematic review and meta‐analysis to examine the efficacy of prebiotics, probiotics, synbiotics and antibiotics in IBS.

MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to July 2017). Randomised controlled trials (RCTs) recruiting adults with IBS, comparing prebiotics, probiotics, synbiotics or antibiotics with placebo or no therapy were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardised mean difference with a 95% CI.

The search identified 4017 citations. Data for prebiotics and synbiotics were sparse. Fifty‐three RCTs of probiotics, involving 5545 patients, were eligible. Particular combinations of probiotics, or specific species and strains, appeared to have beneficial effects on global IBS symptoms and abdominal pain, but it was not possible to draw definitive conclusions about their efficacy. There were five trials of similar design that used rifaximin in non‐constipated IBS patients, which was more effective than placebo (RR of symptoms persisting = 0.84; 95% CI 0.79‐0.90). Adverse events were no more common with probiotics or antibiotics.

Which particular combination, species or strains of probiotics are effective for IBS remains, for the most part, unclear. Rifaximin has modest efficacy in improving symptoms in non‐constipated IBS.

To quantify, through systematic review, the epidemiology and natural history of Crohn’s disease in North America.

The selected articles contained: (i) population‐based samples of patients followed from the time of diagnosis; and (ii) objective diagnostic criteria for disease. Studies on the natural history of Crohn’s disease also contained sufficient follow‐up.

For prevalence studies, data on the incidence, prevalence, gender and age at diagnosis were extracted. For natural history studies, data on the disease activity, use of medications and surgery were extracted.

The prevalence of Crohn’s disease in North America ranges from 26.0 to 198.5 cases per 100 000 persons. The incidence rates range from 3.1 to 14.6 cases per 100 000 person‐years. Most patients have a chronic intermittent disease course, while 13% have an unremitting disease course and 10% have a prolonged remission. Less than half require corticosteroids at any point. During any given year, approximately 10% are treated with corticosteroids and 30% are treated with 5‐aminosalicylates. Up to 57% of patients require at least one surgical resection.

Between 400 000 and 600 000 patients in North America have Crohn’s disease, and the natural history is marked by frequent exacerbations requiring treatment with corticosteroids, 5‐aminosalicylate products and surgery.

Butyrate, propionate and acetate are short chain fatty acids (SCFA), important for maintaining a healthy colon and are considered as protective in colorectal carcinogenesis. However, they may also regulate immune responses and the composition of the intestinal microbiota. Consequently, their importance in a variety of chronic inflammatory diseases is emerging.

To review the physiology and metabolism of SCFA in humans, cellular and molecular mechanisms by which SCFA may act in health and disease, and approaches for therapeutic delivery of SCFA.

A PubMed literature search was conducted for clinical and pre‐clinical studies using search terms: ‘dietary fibre’, short‐chain fatty acids’, ‘acetate’, ‘propionate’, ‘butyrate’, ‘inflammation’, ‘immune’, ‘gastrointestinal’, ‘metabolism’.

A wide range of pre‐clinical evidence supports roles for SCFA as modulators of not only colonic function, but also multiple inflammatory and metabolic processes. SCFA are implicated in many autoimmune, allergic and metabolic diseases. However, translating effects of SCFA from animal studies to human disease is limited by physiological and dietary differences and by the challenge of delivering sufficient amounts of SCFA to the target sites that include the colon and the systemic circulation. Development of novel targeted approaches for colonic delivery, combined with postbiotic supplementation, may represent desirable strategies to achieve adequate targeted SCFA delivery.

There is a large array of potential disease‐modulating effects of SCFA. Adequate targeted delivery to the sites of action is the main limitation of such application. The ongoing development and evaluation of novel delivery techniques offer potential for translating promise to therapeutic benefit.