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Biomedical subjects

Andrew Onderdonk

Publications and source records attributed to Andrew Onderdonk.

8 recordsLinked to original sources

Recommendations for probiotic use.

Probiotics are live microbial organisms that are administrated as supplements or in foods to benefit the host. It is the recommendation that they may be helpful in the prevention and treatment of acute diarrhea in adults and children, the prevention of antibiotic-associated diarrhea in adults and children, and the maintenance of remission and prevention of pouchitis. Although early results indicate that probiotics may also be useful in immunologic modulation to prevent atopy, treatment of radiation intestinal disease, vaginosis, ulcerative colitis, and the irritable bowel syndrome, the studies available are not sufficient to say they are definitely helpful. Even fewer data are available to recommend probiotics for the treatment of H pylori and Crohn disease and for the prevention of cardiovascular risk factors or other degenerative diseases. Clearly, larger and better-designed studies of probiotics are necessary, including comparative and dose-ranging trials.

Cardiovascular Diseases↗

Effect of antibiotics as cholesterol-lowering agents.

Antibiotics were once proposed as hypercholesterolemic agents although the mechanism is unclear, despite broad implications, including providing an alternative approach to cholesterol reduction, with potential relevance for current trials of antibiotics to reduce cardiovascular disease, and possible confounding of routine diagnostic cholesterol measurements. The effect on serum lipids of antibiotics against aerobes and anaerobes, together with possible mechanisms, was therefore explored. Twenty-two men and women took antibiotics for 10 days (either ciprofloxacin for 13 subjects or metronidazole for 10 subjects), with 10 days control in random order separated by 2-week washout periods. Subjects maintained low-fat diets throughout the study. Blood samples and blood pressure were obtained on days 0 and 10 of each phase with 3-day fecal collections and 12-hour breath gas collections at the end of each phase. The results indicated that metronidazole markedly reduced low-density lipoprotein cholesterol (-14.0 +/- 4.0%, P = .006), oxidized low-density lipoprotein (-23.0 +/- 5.1%, P = .002), and the apolipoprotein B/A-I ratio (-18.0 +/- 2.8%, P < .001), whereas the reduction with ciprofloxacin was less pronounced (apolipoprotein B/A-I, -5.0 +/- 1.8%, P = .017). Neither antibiotic altered C-reactive protein or blood pressure. The low-density lipoprotein cholesterol reduction related to an increase in bifidobacteria (r = -0.46, P = .029), but not to markers of colonic fermentation. We conclude that antibiotics can reduce serum lipids acutely. These effects may confound diagnostic measurements but indicate possible links between colonic microflora and blood lipids and the need to study ways of altering colonic microflora by nonantibiotic means as a potential therapeutic option.

Aged↗

Relationship between a toll-like receptor-4 gene polymorphism, bacterial vaginosis-related flora and vaginal cytokine responses in pregnant women.

OBJECTIVE: The relationship between a single nucleotide polymorphism (TLR4 896 A > G) in the toll-like receptor-4 (TLR4) gene, qualitative and quantitative changes in vaginal micro-flora and vaginal interleukin (IL)-1beta and IL-1 receptor antagonist (IL-1ra) concentrations in pregnant women were evaluated. STUDY DESIGN: Qualitative and quantitative microbial methods were used to characterize vaginal micro-flora of 238 women at 18-22 weeks gestation. Polymerase chain reaction was used to determine TLR4 genotype. IL-1beta and IL-1ra concentrations in vaginal lavage samples were measured by ELISA. RESULTS: The TLR4 variant was identified in 10.3% of women. Carriage of this variant was associated with a median increase in vaginal pH (P = 0.05), a greater than 10-fold increase in vaginal Gardnerella vaginalis levels (P < 0.0001) and a 10-fold increase in the vaginal concentration of three species of anaerobic Gram-negative rods, Prevotella, Bacteroides, and Porphyromonas (P = 0.08 ). Colonization with G. vaginalis and/or the anaerobic Gram-negative rods resulted in elevated vaginal IL-1 (P = 0.01) and IL-1ra (P < 0.0002) concentrations in women who were TLR4 896A homozygotes, but not in TLR4 896G carriers. CONCLUSION: The TLR4 896 A > G polymorphism contributes to inter-individual differences in the vaginal immune defense against G. vaginalis and anaerobic Gram-negative rods.

Adenine↗

Innate Immune System Gene Polymorphisms in Women with Vulvovaginal Infections.

The innate immune responses at mucosal surfaces of the lower female genital tract play a central role in preventing the establishment of infection. Variability in the genes regulating innate immune recognition or response to infectious microorganisms could explain interindividual differences in susceptibility to infection and severity of infectious disorders. Of the numerous genetic variations identified within immunoregulatory genes, only a few have so far been studied in relation to infectious disorders of the lower female genital tract. Although these studies broaden our understanding of the genetic influence on mucosal innate immunity and microbiologic outcome, they also highlight the complexity of links between genotypical and phenotypical features, ie, the influence of a single genetic marker on the phenotype is at best moderate and is not constant in every ethnic/racial group. Such inconsistency is primarily attributed to gene-to-gene interactions and demographic genetic variability. Large case-control studies evaluating multiple genetic markers simultaneously in well-defined subgroups will characterize patients more accurately and pave the way to personalized medicine.

Journal Article↗

Ethnic differences of polymorphisms in cytokine and innate immune system genes in pregnant women.

OBJECTIVE: Investigations of the possible role of polymorphic genes in pregnancy outcome may be influenced by ethnic variations in genotype or allele frequencies. Differences in allelic carriage of immune system-related genes among white, black, and Hispanic pregnant women living in New York City and Boston were evaluated. METHODS: DNA was extracted from buccal or vaginal epithelial cells collected from 198 white, 75 black, and 114 Hispanic pregnant women who delivered at term and who had no history of a preterm birth. Genetic polymorphisms in the immunoregulatory genes encoding interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-4, IL-10, IL-1 receptor antagonist (IL-1ra), mannose-binding lectin, toll-like receptor-4, and the 70-kDa heat shock protein were determined. RESULTS: Allele 2 of the IL-1ra gene (IL1RN*2) and IL-4 -590C homozygosity were 4-fold less common in blacks than in whites or Hispanics (P <.001). The IL-4 -590T allele was almost 2-fold more common in Hispanics than in whites (P <.001). The frequency of the 70-kDa heat shock protein 1267G allele was at least 1.4 times greater in blacks compared with whites (P <.001) or Hispanics (P =.002), whereas the homozygous mannose-binding lectin codon 54G allele was observed at least 4.5 times more often in Hispanics compared with whites (P =.007) or blacks (P =.02). CONCLUSION: Investigations of the role of genetic factors affecting pregnancy outcome must be cognizant of ethnic variations when enrolling case and control subjects for studies on allele and genotype frequencies.

Alleles↗