Escherichia coli S fimbriae do not contribute to intestinal colonization or translocation in the gnotobiotic rat.

Escherichia coli S fimbriae, which bind to sialic acid residues, are a virulence factor for extraintestinal infection, but also promote binding to intestinal epithelial cells. In this study, we investigated whether S fimbriae would enhance intestinal colonization by E. coli or promote translocation to extraintestinal sites. A mixture of two E. coli isogenic strains both expressing type-1 fimbriae but differing in the carriage of S fimbriae (Sfim+ and Sfim-) were given perorally to germfree neonatal, infant or adult rats. The Sfim+ bound better to rat intestinal mucus and epithelial cells. However, both strains colonized equally well in both the small and large intestine and their rate of translocation to the mesenteric lymph nodes was similar. Infant rats had higher E. coli levels in the small intestine than adult rats, but their translocation rates were lower. This was at least partly due to their milk diet, since weaned infant rats had more translocating bacteria than infant rats that continued suckling their mother. The results suggest that S fimbriae, despite binding to intestinal epithelial cells and mucus, do not contribute to either colonization or translocation in the gnotobiotic rat.     

Insulin resistance after renal transplantation: impact of immunosuppressive and antihypertensive therapy.

OBJECTIVE: The purpose of the present study was to validate various surrogate estimates of insulin sensitivity (IS) in a renal transplant population and to assess the influence of immunosuppressive and antihypertensive therapy on insulin resistance (IR) after renal transplantation. RESEARCH DESIGN AND METHODS: A total of 167 consecutive renal transplant recipients without previously known diabetes underwent a 75-g oral glucose tolerance test (OGTT) 3 months after renal transplantation. A total of 43 patients also underwent a euglycemic-hyperinsulinemic glucose clamp study. Six OGTT-derived IS indexes were validated against the euglycemic-hyperinsulinemic glucose clamp-derived IS index (ISI(CLAMP)). RESULTS: The OGTT-derived ISI(TX) correlated closely with the ISI(CLAMP) (r = 0.58, P < 0.001). The other surrogate estimates of IS were also significantly but less well correlated with the ISI(CLAMP) (Spearman's correlation; r = -0.45 to 0.41, P = 0.003-0.050). In the univariate model, BMI, daily prednisolone dose, creatinine clearance, hypertension, number of antihypertensive agents, and use of diuretics or beta-blockers were negatively associated with ISI(TX) (P < 0.05). After multiple regression analysis, BMI (P < 0.001), daily prednisolone dose (P < 0.001), cytomegalovirus infection (P = 0.030), and triglycerides (P = 0.034) were shown to be independent predictors of posttransplant IR. CONCLUSIONS: The OGTT-derived ISI(TX) may be a useful estimate of IS in Caucasian renal transplant recipients. Increasing daily prednisolone dose is an independent predictor of IR after renal transplantation. Hypertension and the use of beta-blockers and diuretics may also deteriorate IR in this group of patients.     

Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients

Clostridium difficile-associated disease (CDAD) with frequent watery stools, sometimes with painful bowel movements, fever and sickness, is probably the major known cause of antibiotic-associated diarrhea and colitis, most probably depending on a disruption of the normal intestinal balance in the microbiome. In this study, we have inoculated a mixture of fecal microbes--as an enema--originating from a healthy Scandinavian middle-aged donor, regularly re-cultivated under strict anaerobic conditions for more than 10 years, to 32 patients. Twenty-two patients (69%) were durably cured. In those patients receiving the transplant by colonoscopy, four out of five were cured. To the best of our knowledge, this is the first time a fecal culture of microbes has retained the possibility for years to cure a substantial number of patients with CDAD.     

Calcineurin inhibitor effects on glucose metabolism and endothelial function following renal transplantation

Abstract: Background:  Calcineurin inhibitors (CNI) are involved in the development of post-transplant diabetes mellitus (PTDM). Changes in insulin secretion and sensitivity contribute to the development of PTDM and are associated with endothelial function.
Methods:  In a pre-defined substudy of a previously published randomized trial in renal transplant recipients we compared the effect of CNI treatment (n = 23) with complete CNI-avoidance (n = 21) on insulin secretion and sensitivity (oral glucose tolerance test) as well as endothelial function (laser Doppler flowmetry), 10 wk and 12 months following transplantation.
Results:  Insulin sensitivity differed 10 wk post-transplant and was significantly better after 12 months in patients never treated with CNI drugs [0.091 (0.050) vs. 0.083 (0.036) μmol/kg/min/pmol/L, p = 0.043]. Insulin secretion tended to be higher in CNI treated patients at both time points (p = 0.068). Endothelial function was not significantly different at week 10 [540 (205) vs. 227 (565) arbitary units × minutes, p = 0.35] or month 12 [510 (620) vs. 243 (242), p = 0.33].
Conclusions:  Findings in the present study indicate that long-term CNI treatment negatively affects glucose metabolism and this may contribute to the increased risk for premature cardiovascular disease in CNI treated renal transplant recipients. Further studies to elucidate this hypothesis are, however, needed.     

Tacrolimus-Based, Steroid-Free Regimens in Renal Transplantation: 3-Year Follow-Up of the ATLAS Trial

BACKGROUND: Long-term use of corticosteroids is associated with considerable morbidity, including cardiovascular and metabolic adverse effects. METHODS: This study evaluated the long-term efficacy and safety of two steroid-free regimens compared with a triple immunosuppressive therapy in renal transplant recipients. This was a 3-year follow-up to a 6-month, open-label, randomized, multicenter study. RESULTS: Data from 3 years were available for 421 (93.3%) of 451 patients in the original intent-to-treat population (143 tacrolimus/basiliximab [Tac/Bas], 139 tacrolimus/mycophenolate mofetil [Tac/MMF], and 139 tacrolimus/MMF/steroids [triple therapy]). In the time interval from 6 months to 3 years after transplantation, the incidence of biopsy-proven acute rejection was low and similar (Tac/Bas, 2.1%; Tac/MMF, 2.2%; triple therapy, 2.2%); Most rejection episodes occurred during the first 6 months of the study. Graft survival was high (Kaplan-Meier estimates: 92.7%, 92.5%, and 92.5%), as was patient survival (93.1%, 96.4%, and 97.0%). There were 10 graft losses (n=2, 4, and 4) and 12 patient deaths (n=5, 2, and 5). Renal function was well preserved throughout the study and similar between groups. There was a trend toward improved cardiovascular risk factors in the Tac/Bas group, including reduced total and low-density lipoprotein cholesterol and lower new-onset insulin use. There were no between-group differences in the incidence or type of adverse events. CONCLUSION: Higher rates of acute rejection early in treatment were seen with the steroid-free regimens, but this did not translate into poorer long-term outcomes, such as graft and patient survival and renal function. A trend for a more favorable cardiovascular risk profile was observed for steroid-free immunosuppression with Tac/Bas.     

Ecosystems: development,functions and consequences of disturbances,with special reference to the oral cavity

Abstract. Some general rules for the development and maintenance of microbial ecosystems are outlined. Studies on germ-free animals have given valuable baselines concerning structures and functions in the host per se. The oral cavity represents several consortia of micro-organisms, governed by factors deriving from the host, the diet and/or the micro-organisms. Alterations in these factors, as well as intake of antibiotics, etc., may give disturbances, which can be analyzed according to general guidelines.     

Influence of oral intake of seven different antibiotics on faecal short-chain fatty acid excretion in healthy subjects

Faecal excretion of short-chain fatty acids (SCFAs) has been measured by gas chromatography in groups of six or seven healthy subjects before, during, and after they received the antibiotics bacitracin, co-trimoxazol, doxycycline, erythromycin, nalidixic acid, ofloxazin, or vancomycin orally for 6 days. Intake of bacitracin and vancomycin had pronounced effects on faecal SCFAs excretion and reduced median total concentration of SCFAs from 105.4 mmol/kg to 21.8 mmol/kg and from 69.3 mmol/kg to 19.4 mmol/kg, respectively (p less than 0.05). Erythromycin had moderate effects on the faecal SCFAs excretion, whereas small or no changes were seen during intake of co-trimoxazol, doxycycline, nalidixic acid, and ofloxacin. 2-Methylbutyric acid, a SCFA not previously seen in human faeces, was found in the faeces of all subjects (median concentration before intake of antibiotic, 1.3 mmol/kg). Bacitracin, erythromycin, nalidixic acid, and vancomycin were detected in high concentrations in faeces during therapy, whereas trimethoprim, doxycycline, and ofloxacin were found in relatively low concentrations. In conclusion, some, but not all, peroral antimicrobials induce changes in faecal SCFAs, most likely reflecting changes in the colonic ecosystem.