C. Amadini

Intestinal microflora and oral bacteriotherapy in irritable bowel syndrome

On the basis of many clinical and experimental observations, it would appear feasible to hold that the characteristics of the luminal milieu, the relationship, the balance between luminal prokaryotic cells and mucosal eukaryotic cells and the consequent immunological and humoral local and systemic responses take part in the pathophysiology of several diseases and, consequently bacteriotherapy can play a relevant role in the treatment and prevention of irritable bowel syndrome and more in general, of the intestinal functional disorders. The irritable bowel syndrome is characterised by sudden and unforeseeable changes in the two main symptoms, constipation and diarrhoea, even within a few days. The amount and composition of proximal colon microflora, increasing with regard to the above-mentioned factors, and the time in which this development occurs, are, in our opinion, elements taking part, together with colon dysmotility and alterations of visceral perception, in the onset of the variability in stool frequency, typical of these patients. The present open noncontrolled trial is the first observation showing a clinical improvement related to changes in the composition of the faecal bacterial flora and in faecal biochemistry and, remarkably, in the colonic motility pattern, all of which induced by administration of probiotics, in patients with functional diarrhoea.

Probiotics - Role in inflammatory bowel disease

The aetiology of inflammatory bowel disease is still unclean. Whilst a specific pathogen agent associated with these diseases has not been found, the rationale for probiotic therapy in inflammatory bowel disease is based on convincing evidence involving intestinal bacteria in their pathogenesis. Encouraging results have been obtained with probiotic therapy in several animal models of experimental colitis. The administration of highly concentrated probiotic preparations represents a valid approach both for the prevention of pouchitis onset and relapses. The encouraging results obtained in ulcerative colitis and Crohns disease need to be further assessed in large double-blind trials.

Probiotics for the treatment of postoperative complications following intestinal surgery

Probiotics are living micro-organisms that belong to the normal enteric flora and exert a beneficial effect on health and well-being. The rationale for the therapeutic use of probiotics in pouchitis (the most frequent long-term complication following pouch surgery for ulcerative colitis) and postoperative recurrence in Crohns disease is based on convincing evidence suggesting a crucial role for the endogenous intestinal microflora in the pathogenesis of these conditions. Positive results have been obtained with the administration of highly concentrated probiotic preparations in preventing the onset and relapses of pouchitis. Further controlled studies are needed to establish the efficacy of probiotics in the prophylaxis of postoperative recurrences of Crohns disease and in the treatment of mild pouchitis.

Treatment of mild to moderate ulcerative colitis and pouchitis

The meta‐analyses of published trials have shown topical therapy with 5‐aminosalicylic acid (5‐ASA) to be the treatment of choice in active distal ulcerative colitis. Oral aminosalicylates are effective for both distal and extensive ulcerative colitis, but in distal colitis the rates of improvement and remission are usually lower than those reported for rectal 5‐ASA therapy. An alternative to 5‐ASA therapy is represented by the new steroids; budesonide and beclometasone dipropionate (BDP) enemas, the most extensively studied, have been shown to be as effective as conventional steroids but with a significantly lower inhibition of plasma cortisol. Patients who do not respond to 5‐ASA or new steroids should be treated with oral steroids. Azathioprine or 6‐mercaptopurine may be effective in patients who do not respond or cannot be weaned off steroids. Treatment of pouchitis is largely empirical and few controlled studies have been carried‐out. Antibiotics are the treatment of choice and most patients make a good response to metronidazole or ciprofloxacin. Chronic refractory pouchitis may benefit from a prolonged course of a combination of antibiotics. Highly concentrated probiotics (VSL#3) are effective both for the prevention of pouchitis onset and the prevention of relapses.

Standard Treatment of Ulcerative Colitis

Ulcerative colitis (UC) is an idiopathic, chronic inflammation of the colon which may present with a range of mild to severe symptoms. The disease may be localized to the rectum or can be more extensive and involve the left side of the colon or the whole colon. Treatment in UC is directed towards inducing and maintaining remission of symptoms and mucosal inflammation. The key parameters to be assessed for the most appropriate treatment are the severity and extent of the inflammation. Meta-analyses of published trials have shown that topical treatment with 5-aminosalicylic acid (5-ASA) is the treatment of choice in active distal mild-to-moderate UC. Oral aminosalicylates are effective in both distal and extensive mild-to-moderate disease, but in distal disease, the rates of remission are lower than those obtained with topical 5-ASA. New steroids, such as budesonide and beclomethasone dipropionate (BDP), administered as enemas, constitute an alternative to 5-ASA therapy. In some studies, these have been shown to be as effective as conventional steroids but with significantly lower inhibition of plasma cortisol levels. Patients with unresponsive disease or those with more severe presentation will require oral corticosteroids and sometimes intravenous therapy. Approximately 10% of patients with unresponsive UC have severe attacks requiring hospitalization. Patients with severe disease should be managed jointly by a medical and surgical team, and intensive intravenous treatment should be started with high-dose steroids. Early recognition of failure of therapy will allow the introduction of immunosuppressive therapy with intravenous cyclosporine. Patients who respond are shifted to oral cyclosporine associated with azathioprine/6-mercaptopurine, whereas those who fail will require proctocolectomy. Oral aminosalicylates are the first-line therapy in maintenance of remission. Topical 5-ASA may play a role in distal disease. Patients who are steroid dependent can be started on azathioprine or 6-mercaptopurine although it may take up to 3 months for the treatment to become effective. They may have reversible immediate side effects, such as pancreatitis or bone marrow suppression, which disappear upon discontinuation of therapy. Close monitoring of these hematologic and biochemical parameters will improve safety. The use of biologic therapy with infliximab in more severe disease has not been established.

Monitoring activity in ulcerative colitis

The monitoring of patients with ulcerative colitis is easier than in patients with Crohns disease for several reasons: the severity of symptoms and activity of inflammation tend to run parallel in ulcerative colitis when involvement of the large bowel is more extensive. The easy accessibility of the colonic mucosa by endoscopic and histologic examination provides further information concerning the degree of inflammation. In severe attacks, the patient must be admitted to hospital and monitored carefully. Clinical and laboratory parameters (such as daily stools, CRP, fever, haemoglobin, albumin, etc.) and plain abdominal X‐ray are useful in monitoring the activity of the disease and to predict the outcome. In mild to moderate attacks, endoscopic and histologic evaluation are the best methods for choosing the appropriate treatment and for assessing response.

CXC and CC chemokine expression in inflamed and non-inflamed pelvic ileal pouch tissue

Background and aims Pouchitis is the major long-term complication after ileal pouch–anal anastomosis (IPAA) in patients operated on for ulcerative colitis. The cause is unknown, but both the history of ulcerative colitis and increased bacterial concentration are important factors. Chemokines are mediators for the recruitment of inflammatory cells to the site of inflammation. This study examined the tissue expression of a panel of specific chemokines and the corresponding recruitment of inflammatory cells in IPAA tissue with and without inflammation and after antibiotic treatment.