["Probiotic medicine" and certainty of the evidence.] / "Probiotic medicine" e certezza delle evidenze.

These are excellent times for probiotic medicine. We have discovered more than 150,000 genomes of the microbiome, which can be aggregated into 4,930 species. However, the dream of microbiome-based medicine requires a new approach - an ecological and evolutionary understanding of host-microbe interactions, rather than a qualitative analysis of species. Yet researchers still disagree on what constitutes a healthy microbiome or how to define an altered one. There is still uncertainty as to which properties of the microbiome will represent the most informative biomarkers in clinical and epidemiological studies. And little is known about how the microbiomes of different regions of the body, such as the mouth, intestines or skin, interact. It is time to re-establish the foundations for the certainty of evidence in myocrobiome-based medicine. We believe robust new pillars are needed: starting clinical trials whenever possible; extending the role of N-of-1 trials; ending the "one probiotic for every disease" principle; reduce the number of outcomes of each research; search for the replicability of the results (the best test for the validity of an intervention with probiotics is not statistical significance but the replication of the result). Again, we would like to urge probiotic medicine researchers not to publish in "pirate" journals.

[Side effects of antibiotic: diarrhea and Clostridium difficile infection.] / Effetti collaterali degli antibiotici. Diarrea da antibotici e colite da Clostridium difficile.

Antibiotics are some of the most frequently prescribed medications worldwide, but antibiotic therapy may disturb the colonization resistance of gut microbiota to pathogenic bacteria, resulting in a range of symptoms that include, most notably, diarrhea that occurs between 7% and 33% of adults and 66 and 80% in pediatric patients (median of 22%) who take antibiotics. The diverse class of antibiotics may damage the metabolic homeostasis and can alter the level of intestinal metabolites including amino acids, bile acids, glucose, short chain fatty acids through alteration in abundance of metabolically active bacteria. Clostridium difficile is the main cause of antibiotics associated diarrhea: 3rd generation Cephalosporin, Clyndamicin, 2nd and 4th generation Cephalosporines, Sulfamethoxazole-trimethoprim, Quinolones, Penicillin combination show the strongest association with diarrhea.

[Clostridium difficile infection and chronic inflammatory bowel disease.] / Infezione da Clostridium difficile e malattie infiammatorie croniche intestinali.

Patients with IBD are at increased risk of developing Clostridium difficile (CD) infection and have worse outcomes, including higher rates of colectomy and death, and experience higher rates of recurrence. However, it is still not clear whether CD is a cause of IBD or a consequence of the inflammatory state and of intestinal dysbiosis. The association between IBD and CD may be due to different factors, such as drugs that are used for the treatment of IBD, including repeat courses of antibiotics, that might alter the intestinal flora and promote colonization, altered immune and nutritional status, frequent hospitalizations, and even genetic predisposition. It has been suggested that up to 20% of IBD flares were associated with testing positive for CD and retrospective studies demonstrated doubling of the infection incidence among patients with Crohn Disease, and a 3-fold increase among those with Ulcerative Colitis. They have also shown that the CD infection incidence among IBD patients is estimated as being 3-fold higher than that in the general population. Decreased intestinal microbial diversity along with an inadequate immune response is thought to play a causative role in the development of CD infection.

[Probiotics for the antibiotics associated diarrhea and for Clostridium difficile infection.] / Probiotici per la diarrea da antibiotici e per l'infezione da Clostridium difficile.

The term probiotic refers to live microorganisms that survive passage through the gastrointestinal tract and have beneficial effects on the host. Many strains of probiotic microorganisms have been shown to inhibit growth and metabolic activity as well as the adhesion to intestinal cells of enteropathogenic bacteria, to modulate the gut microbiota and to have immunostimulatory or regulatory properties. The use of probiotic microorganisms for the prevention and the treatment of Antibiotic Associated Diarrhea is an obvious measure and perhaps the most usual application of probiotics. This overview summarizes the most commonly used probiotic microorganisms for DAA and IBD.

Thirty Years of Lactobacillus rhamnosus GG: A Review.

Lactobacillus rhamnosus GG (LGG) was the first strain belonging to the genus Lactobacillus to be patented in 1989 thanks to its ability to survive and to proliferate at gastric acid pH and in medium containing bile, and to adhere to enterocytes. Furthermore LGG is able to produces both a biofilm that can mechanically protect the mucosa, and different soluble factors beneficial to the gut by enhancing intestinal crypt survival, diminishing apoptosis of the intestinal epithelium, and preserving cytoskeletal integrity. Moreover LGG thanks to its lectin-like protein 1 and 2 inhibits some pathogens such as Salmonella species. Finally LGG is able to promote type 1 immune-responsiveness by reducing the expression of several activation and inflammation markers on monocytes and by increasing the production of interleukin-10, interleukin-12 and tumor necrosis factor-α in macrophages. A large number of research data on Lactobacillus GG is the basis for the use of this probiotic for human health. In this review we have considered predominantly randomized controlled trials, meta-analysis, Cochrane Review, guide lines of Scientific Societies and anyway studies whose results were evaluated by means of relative risk, odds ratio, weighted mean difference 95% confidence interval. The effectiveness of LGG in gastrointestinal infections and diarrhea, antibiotic and Clostridium difficile associated diarrhea, irritable bowel syndrome, inflammatory bowel disease, respiratory tract infections, allergy, cardiovascular diseases, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, cystic fibrosis, cancer, elderly end sport were analyzed.

[Evidence-based medicine vs personalized medicine.] / Evidence-based medicine vs medicina personalizzata.

Evidence-based medicine (EBM) and personalized medicine (PM) are driven by two diverse modes of reasoning about «evidence making¼. EBM has been criticized since his quality mark has been misappropriated by vested interests, the benefits statistically significant may be marginal in clinical practice, rigid rules and technology may produce care that is management driven rather than patient centered. On the contrary PM (or "precision medicine") refers to the tailoring of medical treatment to the specific characteristics of each patient involving the ability to classify individuals into subpopulations that are uniquely susceptible to a specific treatment, sparing expense and side effects and is derived from doubts on the results of subgroup analyses and on non responders in clinical trials typical of EBM. While both paradigms are epistemically sound they cannot, and should not, be hybridized into a unique model. Rather they ought to represent two compatible, but alternative ways of informing the Clinical practice. The clinicians may expect to see their responsibility increasing as they will deal with diverse, but equally compelling ways of reasoning and deciding about which intervention will qualify as the «best one¼ in each individual case.

[Revival of evidence-based medicine in gastroenterology.] / Per la rinascita della evidence-based medicine in gastroenterologia.

The evidence-based medicine (EBM) in gastroenterology is born with the XIII International Congress of Gastroenterology, the world congress of Gastroenterology, held in Rome in 1988. A clinical epidemiology manual was placed in the congress bag for each participant. The book contained an approach to biostatistics, interpretation of epidemiological data, clinical trials, meta-analysis and decision analysis. In the pocket appeared for the first time a floppy disk that offered softwares for the analysis of Student's and χ2, for randomization and for meta-analysis. In the following years the clinical epidemiology courses of Torgiano were born, now arriving at the 18th edition. The dedicated EBGH.it portal was also born. The reflections of recent years have suggested 8 theses for the renaissance of EBM in gastroenterology. 1. The patient must return to the center of the EBM. 2. There is an urgent need for more efficient production and implementation of evidences. 3. Researchers in gastroenterology should start studies only in relevant clinical fields where are not yet sufficient answers. 4. The EBM must move towards the evidence on the different effects of an intervention. 5. The relevance of the P-value should be reconsidered. 6. Precision medicine is growing. But EBM can not wait. 7. The best validity test is not the significance but the reproducibility of the data. 8. Data from the real world (real world evidence) can help increase the validity of clinical results.