Functional bowel disorders (FBD), mainly irritable bowel syndrome (IBS) and functional constipation (FC, also called chronic idiopathic constipation), are very common worldwide. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, although less common, has a strong impact on patients' quality of life, as well as being highly expensive for our healthcare. A definite cure for those disorders is still yet to come. Over the years, several therapeutic approaches complementary or alternative to traditional pharmacological treatments, including probiotics, prebiotics, synbiotics, fibre and herbal medicinal products, have been investigated for the management of both groups of diseases. However, most available studies are biased by several drawbacks, including small samples and poor methodological quality. Probiotics, in particular Saccharomyces boulardii and Lactobacilli (among which Lactobacillus rhamnosus), synbiotics, psyllium, and some herbal medicinal products, primarily peppermint oil, seem to be effective in ameliorating IBS symptoms. Synbiotics and fibre seem to be beneficial in FC patients. The probiotic combination VSL#3 may be effective in inducing remission in patients with mild‐to‐moderate ulcerative colitis, in whom Escherichia coli Nissle 1917 seems to be as effective as mesalamine in maintaining remission. No definite conclusions can be drawn as to the efficacy of fibre and herbal medicinal products in IBD patients due to the low number of studies and the lack of randomized controlled trials that replicate the results obtained in the individual studies conducted so far. Thus, further, well‐designed studies are needed to address the real role of these therapeutic options in the management of both FBD and IBD.Linked Articles: This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc

Background: Digestive enzymes are able to break down proteins and carbohydrates and lipids, and their supplementation may play a role in the management of digestive disorders, from lactose intolerance to cystic fibrosis. To date, several formulations of digestive enzymes are available on the market, being different each other in terms of enzyme type, source and origin, and dosage. Methods: This review, performed through a non-systematic search of the available literature, will provide an overview of the current knowledge of digestive enzyme supplementation in gastrointestinal disorders, discussion of the use of pancreatic enzymes, lactase (-galactosidase) and conjugated bile acids, and also exploring the future perspective of digestive enzyme supplementation. Results: Currently, the animal-derived enzymes represent an established standard of care, however the growing study of plant-based and microbe-derived enzymes offers great promise in the advancement of digestive enzyme therapy. Conclusion: New frontiers of enzyme replacement are being evaluated also in the treatment of diseases not specifically related to enzyme deficiency, whereas the combination of different enzymes might constitute an intriguing therapeutic option in the future.

Antibiotics are mainly used in clinical practice for their activity against pathogens, but they also alter the composition of commensal gut microbial community. Rifaximin is a non-absorbable antibiotic with additional effects on the gut microbiota about which very little is known. It is still not clear to what extent rifaximin can be able to modulate gut microbiota composition and diversity in different clinical settings. Studies based on culture-dependent techniques revealed that rifaximin treatment promotes the growth of beneficial bacteria, such as Bifidobacteria and Lactobacilli. Accordingly, our metagenomic analysis carried out on patients with different gastrointestinal and liver diseases highlighted a significant increase in Lactobacilli after rifaximin treatment, persisting in the short time period. This result was independent of the disease background and was not accompanied by a significant alteration of the overall gut microbial ecology. This suggests that rifaximin can exert important eubiotic effects independently of the original disease, producing a favorable gut microbiota perturbation without changing its overall composition and diversity.

Liver lipid metabolism and its modulation are involved in many pathologic conditions, such as obesity, non-alcoholic fatty liver disease, diabetes mellitus, atherosclerosis and cardiovascular disease. Metabolic disorders seem to share a similar background of low-grade chronic inflammation, even if the pathophysiological mechanisms leading to tissue and organ damage have not been completely clarified yet. The accumulation of neutral lipids in the liver is now recognized as a beneficial and protective mechanism; on the other hand, lipoperoxidation is involved in the development and progression of non-alcoholic steatohepatitis. The role of the gut microbiota in liver lipid metabolism has been the object of recent scientific investigations. It is likely that the gut microbiota is involved in a complex metabolic modulation and the translocation of gut microflora may also contribute to maintaining the low-grade inflammatory status of metabolic syndrome. Therefore, lipid metabolism pathology has vague limits and complex mechanisms, and the knowledge of these is essential to guide diagnostic and therapeutic decisions.

Liver cirrhosis is a paradigm of intestinal dysbiosis. The qualitative and quantitative derangement of intestinal microbial community reported in cirrhotic patients seems to be strictly related with the impairment of liver function. A kind of gut microbial “fingerprint”, characterized by the reduced ratio of “good” to “potentially pathogenic” bacteria has recently been outlined, and is associated with the increase in Model for End-Stage Liver Disease and Child Pugh scores. Moreover, in patients presenting with cirrhosis complications such as spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and, portal hypertension intestinal microbiota modifications or the isolation of bacteria deriving from the gut are commonly reported. Rifaximin is a non-absorbable antibiotic used in the management of several gastrointestinal diseases. Beyond bactericidal/bacteriostatic, immune-modulating and anti-inflammatory activity, a little is known about its interaction with gut microbial environment. Rifaximin has been demonstrated to exert beneficial effects on cognitive function in patients with HE, and also to prevent the development of SBP, to reduce endotoxemia and to improve hemodynamics in cirrhotics. These results are linked to a shift in gut microbes functionality, triggering the production of favorable metabolites. The low incidence of drug-related adverse events due to the small amount of circulating drug makes rifaximin a relatively safe antibiotic for the modulation of gut microbiota in advanced liver disease.