COVID-19 and the enteric system: rapidly propagating issues.

The newly described SARS-CoV-2 respiratory virus is now righteously presenting as an ominous threat, based on the speed with which it originated a zoonosis from bats; advancing at a similar rate, the virus has placed mankind before a pandemic, with an infection toll of some 431 million, and a lethality of 5,9 million (as of February 25, 2022). The size of the harm that this agent can unleash against us is appallingly wide, from brain ischemia to foot chilblain, passing by heart massive infarction. Designing a possible response, we reappraised the well-known equation depression-inflammation, and tested the hypothesis that an upgraded ease-of-mind might help reduce the host's hospitality towards SARS-CoV-2. With time passing, it becomes increasingly evident that the virus shall tend to progressively occupy spaces, replacing pandemics with an apparently calm endemicity. This will have to be avoided, and surveillance of society on psychological terms will be one tenet. Needless to say, the role of the enteric tract in these issues is growing higher, and it will be narrated to seal the matters with the last (not the least) touch of glue.

Modulation of the gut microbiota: opportunities and regulatory aspects.

The human gut is an intensively colonized organ containing microorganisms that can be health-promoting or pathogenic. This feature led to the development of functional foods aiming to fortify the former category at the expense of the latter. Since long, cultured products, including probiotics fortification, have been used for humans as live microbial feed additions. This review presents some of the microbes used as probiotics and discusses how supplementation with probiotics may help initiate and/or restore eubiotic composition of gut microbiota. Additionally, it considers safety and regulatory aspects of probiotics.

COVID-19: a user's guide, status of the art and an original proposal to terminate viral recurrence.

The world is now entering its 9th month of combat against a pandemic of deadly pneumonia. Started out from China in December 2019, the disease has been declared as caused by infection with a so far unknown RNA Coronavirus of the respiratory family, then named severe acute respiratory syndrome coronavirus SARS-CoV-2. In the absence of a vaccine, and with scientists still struggling for an effective therapy, COVID-19 (the SARS-dependent syndrome) carries up to now, a death toll of more than 590,000 (July 18,2020) undermining jobs and finance of contemporary society in all continents. Social distancing, the only measure hitherto shown to restrain virus spread, has been progressively loosened from May 2020 in some countries, leaving us in the fear of repeat attacks from the unchecked virus. We discuss the problem and propose to tentatively boost the antivirus cell machinery by using lab-made viral mimics to engage cell receptors.

The gut and the inflammatory bowel diseases inside-out: extra-intestinal manifestations.

An increasing deal of attention is being conveyed on the extra-intestinal manifestations (EIM) of inflammatory bowel diseases (IBD). We compiled the present review in an attempt to upgrade the accuracy of the classification of such polymorphic entities. We focused on three patterns. First, the conventional EIM localized to bone and joints, to the eye, to the biliary tree and to the skin. Second, the so-called IBD-like syndromes accompanied by bone marrow-derived anomalies of innate or acquired immunity. Third, specific disorders of the skin and of the lungs. EIM are thought to derive from an altered gut permeability, the release of cross-reacting antigens, and subsequent peripheral inflammation; T helper 17 cells boosted by a polymorphic interleukin 23 circuitry would be the main effectors of this chain. Inflammatory bowel disease-like pictures would derive from inborn errors of the immune response causing undue inflammation home to the gut. Monogenic IBD belong to this subset, and are of specific pediatric interest. Psoriasis, chronic obstructive pulmonary disease, and IBD are all inflammatory disorders of the barrier organs: skin, lungs, and gut. The demonstration that specific antigen hyper- or hyporesponsiveness raised at any of the three districts can modulate the response of the other two sites, has led to the innovative concept of a system-wide mucosal immunological organ. An improved knowledge of these entities has not only a speculative importance, but can also bear a clinical impact, insofar as EIM prove often more disabling than the underlying IBD itself.

Inflammatory bowel disease: Efficient remission maintenance is crucial for cost containment.

The inflammatory bowel diseases (IBD) are chronic incurable inflammatory disorders of the gut. Some 10% run a downhill course, requiring emergency medical support and often surgery; another small subset are monogenic, and, threatening pediatric patients, are the challenge of these days. The majority of the IBDs, however, are polygenic low-penetrance diseases, running a lifetime waxing-and-waning course. The prevalent trend is towards a slow worsening and steady cost increase. Each and all drugs of the available arsenal exhibit strengths and weaknesses: Mesalamines are chiefly effectively for mild-moderate colitis, and do not work in Crohn's; steroids do not control some 40% of the ulcerative colitis cases, and are not indicated for Crohn's; thiopurines are effective in the maintenance of the IBDs but do not prevent relapses on withdrawal; biologics are still being used empirically (not monitored) causing further increase of their cost over that of hospitalization. Against all these caveats, two simple rules still hold true: Strict adherence maintenance and avoidance of colitogenic drugs. This matter is expanded in this minireview.

The pathologic galaxy modulating the genotype and phenotype of inflammatory bowel disease: comorbidity, contiguity, and genetic and epigenetic factors.

The inflammatory bowel diseases (IBDs) are being seen as a gut inflammatory hub occurring: 1) with inflammatory spots in the eyes, skin, liver, joints (extra-intestinal manifestations); 2) with functionally contiguous disorders such as psoriasis and lung disease (barrier organ diseases); 3) as the consequence of genetic loss of non-redundant cell functions that are critical for gut homeostasis and defense (monogenic IBD). Recent multidisciplinary analysis, fostered by the input of genomic search, has helped hypothesize two pathogenetic models for the main phenotypes of IBDs. In ulcerative colitis, an increased mucosal permeability would prevail, allowing arousal of inflammation from the hyper-reactive underneath lymphoid tissue; an impaired bacterial sensing by innate immunity cells would by contrast place Crohn's disease (CD) in the chapter of the immune deficiency disorders, with the activity phases (the actual target of traditional immune suppressive strategies) representing just "zenith" phases in the continuously waxing-and-waning course of the attempts of the blunted inflammatory machinery to clear the invaders. Studying such errors of innate immunity, a few open-minded investigators have observed that they might not be a CD exclusivity at all: the proven evidence of CD-like pictures in a plethora of granulomatous disorders has thus been consolidated. This scenario calls for a concept of "syndrome" to best be accounted for, and to encourage the envisaging of the future therapy for IBD.

Inflammatory bowel disease: Traditional knowledge holds the seeds for the future.

Despite the level of sophistication they have reached nowadays, the available tools for treatment of inflammatory bowel disease (IBD) can at best chronicize the disease but not cure it. Chances to make leap forward from this hold-back may include designs to reach personalized treatment strategies taking advantage of modern genome associated studies, and shift resources towards unfolding inciting pathogenetic steps rather than continuing to develop drugs that address down-stream phenomena. We have arbitrarily chosen to scrutinize a few projects that may make their way in 2015 and mark the history of IBD research. The list includes: the role of appendix as a regulating factor in pathogenesis of ulcerative colitis/proctitis; the reappraisal of (auto)immune phenomena in the era of microbiome; projects to treat IBD by stem cell infusion; recognition of the crucial pathogenetic role of gut microbiome, and attempts to modify it to treat enteric diseases, from clostridium difficile infection to IBD.

Inflammatory bowel diseases: Current problems and future tasks.

Current knowledge on inflammatory bowel disease (IBD) is mainly endorsed by controlled trials and epidemiologic studies. Yet, we seldom look at the messages from real-world practice. Among a patient population followed since 2008, we looked at an unselected sample of 64 IBD patients [26 Crohn's disease (CD) and 38 ulcerative colitis (UC)] who had been seen as out-patients in the last year. Inducing remission, mesalamines (86% for UC/69% for CD/33%-16% as MMX formulation) prevailed as prescriptions; steroids (55%/19% for UC/CD) ranked second. Prescription of third-party drugs (antibiotics, NSAIDs, biologics) and adherence, were issues in the maintenance. 34% of CD, and 23% of UC patients showed accompanying immunologic diseases: CD-associated familiar psoriasis (4:9) ranked first. Main Message. The association between IBD (CD mainly) and psoriasis, now found in our practice, matches current basic science gathering IBD together with psoriasis (and perhaps chronic respiratory disease) under the comprehensive term "barrier organ disease" wherein an epithelial surface with sensor systems rules contacts between outer antigens and a reactive underneath tissue, with the balance between inflammation and quiescence kept at any time by mucosal permeability. IBD is thus viewed as a polyfactorial/polygenic/syndromic disorder, embedded into a galaxy of immune conditions offering multiple points of attack. This mindset of splitting the IBDs into pathogenic categories may allow overcoming the uniformly targeting of a single cytokine by biological drugs, in favor of demarcating the boundaries between different disease-subtype-specific indications, and paving the way to future personalized strategies.

The gut microbiome.

Since the discovery and use of the microscope in the 17(th) century, we know that we host trillions of micro-organisms mostly in the form of bacteria indwelling the "barrier organs" skin, gut, and airways. They exert regulatory functions, are in a continuous dialogue with the intestinal epithelia, influence energy handling, produce nutrients, and may cause diabetes and obesity. The human microbiome has developed by modulating or avoiding inflammatory responses; the host senses bacterial presence through cell surface sensors (the Toll-like receptors) as well as by refining mucous barriers as passive defense mechanisms. The cell density and composition of the microbiome are variable and multifactored. The way of delivery establishes the type of initial flora; use of antibiotics is another factor; diet composition after weaning will shape the adult's microbiome composition, depending on the subject's life-style. Short-chain fatty acids participate in the favoring action exerted by microbiome in the pathogenesis of type-2 diabetes and obesity. Clinical observation has pinpointed a sharp rise of various dysimmune conditions in the last decades, including IBD and rheumatoid arthritis, changes that outweigh the input of simple heritability. It is nowadays proposed that the microbiome, incapable to keep up with the changes of our life-style and feeding sources in the past few decades might have contributed to these immune imbalances, finding itself inadequate to handle the changed gut environment. Another pathway to pathology is the rise of directly pathogenic phyla within a given microbiome: growth of adherent E. coli, of C. concisus, and of C. jejuni, might be examples of causes of local enteropathy, whereas the genus Prevotella copri is now suspected to be linked to rise of arthritic disorders. Inflammasomes are required to shape a non colitogenic flora. Treatment of IBD and infectious enteritides by the use of fecal transplant is warranted by this knowledge.

Antibiotics and non-steroidal anti-inflammatory drugs in outpatient practice: indications and unwanted effects in a gastroenterological setting.

OBJECTIVE: To explore the type and frequency of the unwanted effects following use of non-steroidal antiinflammatory drugs (NSAIDs) and antibiotics in a gastroenterological out-patient setting. METHODS: We analyzed a gastroenterological database which includes 151 inflammatory bowel disease (IBD) patients followed between January 2008 and December 2009. The key-words included NSAIDs and antibiotics. RESULTS: Of 19 cases treated with NSAIDs, 8 displayed convincing evidence linking them with the subsequent development of IBD. Of 44 antibiotic mentions, 7 documents alluded to macrolide prescriptions, which were followed by induction or relapse of IBD in 5; all of the newly diagnosed cases of IBD were endoscopically proven, and one ran a fulminant course requiring emergency colectomy; 4 of 5 prescriptions of amoxycillin/clavulanic acid were accompanied by toxicity (three hepatitides and one reactivated IBD). Overall, the frequency of unwanted effects was 36% for both NSAIDs and antibiotics. CONCLUSION: We suggest that NSAIDs and antibiotics (specifically of the macrolide structure) can induce gut and hepatic damage, significantly enhancing co-morbidities in gastroenterologic out-patients, with break of cost-containment guidelines. Therefore, caution is advisable in prescribing NSAIDs and antibiotics in this setting. Though retrospective and possibly biased, the current data coincide with both bench work and epidemiological evidence.