Calcium butyrate: Anti-inflammatory effect on experimental colitis in rats and antitumor properties.

Butyric acid is a physiological component of the colonic environment that possesses anti-inflammatory and antitumor properties, among others. However, little is known regarding its effects following direct application on the colonic surface. This study was conducted to investigate the topical anti-inflammatory effect of calcium butyrate in chemically-induced colitis in rats and to evaluate its antitumor properties in vivo and in vitro. The anti-inflammatory activity of calcium butyrate was evaluated in dinitrobenzene sulfonic acid-induced colitis in rats, following intracolonic instillation for 6 consecutive days and its in vivo antitumor activity was evaluated in F344 rats with the azoxymethane (AOM)-induced aberrant crypt foci (AFC) test, following intracolonic instillation for 4 weeks. The in vitro antiproliferative activity was assessed by incubation for 48 h with the HT29, SW620 and HCT116 intestinal tumour cell lines to evaluate the rate of 3H-thymidine uptake. In dinitrobenzene-induced colitis, the intracolonic instillation of calcium butyrate completely prevented body weight reduction in the animals and counteracted the local noxious effects of the irritant by reducing colon edema (-22.7%, P=0.048) and the area of mucosal damage (-48%, P=0.045). In the AOM-induced AFC test, the intracolonic instillation of calcium butyrate significantly reduced the number of AFC in the entire colon (-22.7%, P<0.05). Calcium butyrate, following incubation with the HT29, SW620 and HCT116 tumour cell lines, induced a significant antiproliferative, dose-dependent effect (P=0.046 to P=0.002) in all three strains, as measured by the reduction in 3H-thymidine uptake. Calcium butyrate directly applied to the mucosa of the rat colon was able to ameliorate colonic inflammation, suggesting a possible beneficial role in the treatment of inflammatory colon diseases. Moreover, calcium butyrate exhibited notable antitumor effects in vivo and in vitro; however, their clinical relevance requires confirmation by additional clinical investigations.

Bacteriocin-producing oral streptococci and inhibition of respiratory pathogens.

The use of bacteria as probiotics is in continuous development, thanks to their capacity to maintain or restore a host's natural microbiome by interference with and/or inhibition of other microorganisms mediated by antimicrobial peptide production such as bacteriocins. In the oral cavity, Streptococcus salivarius, a non-pathogenic and predominant oral species, is one of the major bacteriocin producers that is able to coexist in this environment and reduce the frequency of colonization of the main pathogens involved in upper respiratory tract infections. The aim of this study was to screen oral bacteria colonizing healthy children for their use as potential oral probiotics. Eighty-one α-hemolytic streptococci isolated from nasal and/or pharyngeal swabs of 31 healthy children aged between two and twelve years were isolated. Among them, 13 α-hemolytic streptococci were selected for their bacteriocin-like inhibitory activity against potential pathogens. These strains were tested for bacteriocin production and assayed for their capacity to adhere to HEp-2 cell lines. Our data showed that 13 bacteriocin producer strains were able to inhibit different gram-positive pathogens. Among them one strain, S. salivarius 24SMB, deposited as DSM 23307, was selected as a potential oral probiotic, thanks to its safety assessment, ability to inhibit Streptococcus pneumoniae and the absence of virulence and antibiotic resistance genes.

Efficacy of intracolonic administration of low-molecular-weight heparin CB-01-05, compared to other low-molecular-weight heparins and unfractionated heparin, in experimentally induced colitis in rat.

PURPOSE: Parenteral administration of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) resulted effective in improving the symptoms of experimental colitis in rat. Today, there is little information about their activity by intracolonic instillation. The scope of this study was to evaluate the ability of CB-01-05 (a LMWH with a mean molecular weight of about 5,700), compared to a series of other LMWHs and to UFH, directly instilled into the distal colon of the rat, to ameliorate dinitrobenzene (DNB)-induced experimental colitis. METHOD: Adult male Wistar rats underwent colitis induction by intracolonic instillation of DNB. Starting 24 h after colitis induction, CB-01-05 (0.005-0.9 mg), other LMWHs (0.3-0.6 mg), and UFH (0.6 mg) were instilled, by rectal route, into the distal colon once a day for three consecutive days. On the day following the last administration, the animals were sacrificed and the distal colon was isolated, weighed, macroscopically examined, and processed for histology. Additional experiments in rat splenocytes, performed in order to elucidate the anti-inflammatory mechanisms of CB-01-05, were performed. RESULTS: Among the tested items, only CB-01-05 at doses ranging from 0.2 to 0.9 mg was significantly effective in reducing colon weight increase and in improving both the mucosal damaged area and the histological score. The other LMWHs resulted far less effective, showing decreasing activity closely related with the decrease of their molecular weight, thus demonstrating their biological nonequivalence. CB-01-05 resulted also more active than UFH. CB-01-05 was shown to interfere with cytokines production by rat splenocytes, mainly inhibiting interferon (IFN)-gamma expression. CONCLUSIONS: CB-01-05 instilled into the colon is well tolerated, has strong anti-inflammatory effect on DNB-induced colitis in rat, and is the most effective agent among other LMWHs and UFH. These results suggest that the anti-inflammatory activity of CB-01-05, together with its topical administration, could represent a new approach in the management of ulcerative colitis.