The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects.

Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV+ viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART+) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV- controls (HIV-), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study. We assessed fecal microbiota composition using deep 16S rRNA gene sequencing and several immunological and genetic markers involved in HIV immunopathogenesis. The short dietary supplementation attenuated HIV-associated dysbiosis, which was most apparent in VU individuals but less so in ART+ subjects, whose gut microbiota was found more resilient. This compositional shift was not observed in the placebo arm. Significantly, declines in indirect markers of bacterial translocation and T-cell activation, improvement of thymic output, and changes in butyrate production were observed. Increases in the abundance of Faecalibacterium and Lachnospira strongly correlated with moderate but significant increases of butyrate production and amelioration of the inflammatory biomarkers soluble CD14 and high-sensitivity C-reactive protein, especially among VU. Hence, the bacterial butyrate synthesis pathway holds promise as a viable target for interventions.

Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.

Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients.

Expression of gut-homing ß7 receptor on T cells: surrogate marker for microbial translocation in suppressed HIV-1-infected patients?

OBJECTIVES: In view of the fact that mucosal damage associated with HIV-1 infection leads to microbial translocation despite successful antiretroviral treatment, we analysed microbial translocation and expression of the gut-homing ß7 receptor on peripheral T cells in HIV-1-infected individuals. METHODS: Fifteen long-term suppressed HIV-1-infected patients, of whom seven had their treatment intensified with maraviroc and eight with raltegravir, were included in the study. Samples at baseline, at week 48 of intensification, and at weeks 12 and 24 after deintensification were analysed for soluble CD14, lipopolysaccharide (LPS), LPS-binding protein, gut-homing ß7 receptor and T-cell subsets. RESULTS: The increases in both microbial translocation and expression of the gut-homing ß7 receptor on activated CD8 T cells found during maraviroc intensification were reduced after deintensification. Moreover, the correlations between activated ß7(+) T cells and LPS levels found during intensification with maraviroc (P = 0.036 and P = 0.010, respectively) were lost during deintensification. In contrast, microbial translocation was stable during raltegravir intensification, with the exception of decreased LPS levels and activated CD4 ß7(+) T cells, which reverted to baseline values after deintensification. CONCLUSIONS: Microbial translocation is an important factor in gut immune activation and mucosa inflammation, as evidenced by the association between the dynamics of microbial translocation and activated T cells expressing the gut-homing ß7 receptor. The recruitment of activated ß7(+) T cells to the gut tract when alteration of microbial translocation is maximum may be the major mechanism for recovery of mucosal integrity.

[Ulcerative colitis associated with autoimmune hepatitis: a differential form of inflammatory bowel disease?]. / Colitis ulcerosa asociada a hepatitis autoinmune: ¿una forma diferencial de enfermedad inflamatoria intestinal?

Inflammatory bowel Disease (IBD) is a group of chronic inflammatory diseases that can be associated with different autoimmune diseases, including autoimmune hepatitis (AIH). Some specific and differential characteristics in children with IBD associated to AIH have been described. Our aim is to describe the clinical pattern of this association observed in our patients, confirming its differential characteristics as compared to classical IBD in children.

Clinical validation of a multiplex real-time PCR assay for detection of invasive candidiasis in intensive care unit patients.

BACKGROUND: New techniques, such as those based on multiplex quantitative real-time PCR (MRT-PCR), can improve the detection of invasive candidiasis (IC). METHODS: We prospectively studied 63 intensive care unit patients with suspected IC and 40 healthy controls. Blood cultures and MRT-PCR were performed at day 0 and +2, +7, +14 and +21 days in all patients. In addition, ß-d-glucan (BDG) and Candida albicans germ tube antibody (CAGTA) were quantified. RESULTS: IC was confirmed in 27 patients. Colonization was significantly higher in patients with IC (96% versus 64%, P = 0.002). The sensitivity, specificity, positive predictive value and negative predictive value of MRT-PCR for the diagnosis of IC were 96.3%, 97.3%, 92.8% and 98.7%, respectively. The positive predictive value and specificity were significantly higher for MRT-PCR than for BDG and CATGA. MRT-PCR performed very well, especially in deep-seated IC (sensitivity 90.9% versus 45.4% for blood culture; P = 0.06). As regards the most appropriate clinical sample for DNA amplification, in this study whole blood and serum presented similar results. CONCLUSIONS: MRT-PCR appears to be a useful test for confirming a diagnosis of IC in critically ill patients, especially in those with deep-seated disease. Its high sensitivity and positive predictive value make it a much more efficient tool for the management of IC than other diagnostic procedures and clinical scores.

[A missing name in the history of chagasic megaesophagus: Joseph Cooper Reinhardt (1809/10-1873)]. / Um nome que faltava na história do megaesôfago chagásico: Joseph Cooper Reinhardt (1809/10-1873).

The book entitled "Brazil and the Brasilians", written by the Reverends Kidder and Fletcher and firstly published in the United States in 1857, reports the travels of these two missionaries throughout Brazil and includes a section entitled "A new disease". This section contains data regarding the clinical picture, the natural history and the epidemiology of a commom disease in Brazilian hinterland, which was known as "mal de engasgo". These informations were collected in 1855 by Rev. Fletcher from an anonymous North American physician, who worked in Limeira, State of São Paulo, and is called in the book merely as "Dr.-". The present work reports the results of an investigation carried out aiming at the identification of "Dr.-" and discloses documental evidence that "Dr.-" was actually Dr. Joseph Cooper Reinhardt (1809/10-1883). Dr. Reinhardt worked for many years in the citites of Limeira and Campinas, State of São Paulo, and probably had an extensive knowledge regarding the main features of this particular disease, which would be known, nearly 100 years later, as chagasic megaesophagus. The authors point out that, from now on, any account of the history of chagasic megaesophagus must include the name of Dr. Joseph Cooper Reinhardt.

Clinical use of Norgestomet ear implants or intravaginal pessaries for synchronization of estrus in anestrous dairy goats.

Ear implants that contained 3 mg Norgestomet or vaginal pessaries that contained 40 or 45 mg fluorogestone acetate were used to induce estrus in dairy goats in three herds in May. Ear implants or vaginal pessaries were left in place for 11 d. Cloprostenol (50 mug) and PMSG (500 IU) were administered i.m. 24 h prior to removal of ear implants or vaginal pessaries. After removal of vaginal pessaries, onset of standing estrus occurred in 22 23 goats (96%) at 20 +/- 4.7 h, in 19 20 goats (95%) at 22 +/- 6.3 h, and in 16 16 goats (100%) at 19 +/- 1.2 h in Herds A, B and C, respectively. After removal of ear implants, onset of standing estrus occurred in 25 25 goats (100%) at 19 +/- 4.9 h, in 20 22 goats (91%) at 22 +/- 7.0 h, and in 15 15 goats (100%) at 18 +/- 2.2 h in Herds A, B and C, respectively. Does were bred by natural service in Herds A and B, and by artificial insemination 28 h after vaginal pessary or ear implant removal in Herd C. Pregnancy rates were determined 39 to 53 d post breeding by real-time ultrasound. Pregnancy rates in goats with vaginal pessaries were 32, 55 and 6%; and in goats with ear implants they were 56, 67 and 27% in Herds A, B and C, respectively. Problems encountered included poor libido in some bucks, abortions in undersized yearling does, and loss of ear implants by three does (not included in the data). Statistically there was no difference in pregnancy rates between goats receiving vaginal pessaries or ear implants (P>0.10).

Scrotal circumference, seminal characteristics, and testicular lesions of yearling Angus bulls.

The effect of age and body weight on scrotal circumference (SC), the effect of SC on percentage of sperm abnormalities and seminal characteristics, and the relationship of SC with testicular weight, epididymidal weight, degree of germinal epithelial loss (DGEL), and percentage of tubules graded 4 or greater (G4+) were studied in 37 Angus bulls. All bulls were from one herd and were examined at monthly intervals, during a 140-day weight gain test starting when they were 11 months old. The study was terminated when the bulls were slaughtered at 14 months of age. As age and body weight increased, SC increased (P less than 0.001). The incidence of sperm abnormalities decreased (P less than 0.001) as SC increased; however, seminal characteristics remained poor in bulls with SC less than or equal to 32 cm. Pathologic changes in 600 cross sections of seminiferous tubules from each bull were classified into 9 grades. The DGEL per 100 tubules was calculated by assigning a value to each grade according to the severity of loss of germinal epithelium. Tubules classified as G4+ were devoid of germinal cells and provided an index of irreversible loss of germinal epithelium. The SC was correlated positively with testicular weight (r = 0.91, P less than 0.001) and epididymal weight (r = 0.59, P less than 0.001) and negatively with DGEL (r = -0.48, P less than 0.01) and G4+ (r = -0.44, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Synchronization of estrus and fertility in goats with norgestomet ear implants.

Estrus was synchronized in 64 dairy goats in July with norgestomet ear implants. Half the does received ear implants that contained 6 mg norgestomet and the remaining does received implants that contained 3 mg. Implants were left in place for 11 days. Each doe received i.m. injections of 400 IU PMSG and 50 mug cloprostenol 24 hours prior to implant removal. Twenty-eight of 32 does (87.5%) that received 6 mg or 3 mg norgestomet exhibited onset of estrus within 24 hours of implant removal. All does had exhibited onset of standing estrus by 43 hours after implant removal. Does were hand-mated to fertile bucks twice daily while in standing estrus. There were no differences between does implanted with 6 mg or 3 mg in fertility to the induced estrus (74.2% vs 75% kidding), mean length of gestation (151.0 +/- 3.2 vs 151.6 +/- 2.0 days), mean number of kids per doe (2.1 +/- 0.8 vs 2.3 +/- 0.7) or in mean kid weights (3.10 +/- 0.80 vs 3.06 +/- 0.86 kg) (6 mg vs 3 mg, respectively). It was concluded that ear implants that contained 3 mg of norgestomet were equally as effective as implants that contained 6 mg for synchronization of estrus in dairy goats.