Diversity and Composition of the Adult Fecal Microbiome Associated with History of Cesarean Birth or Appendectomy: Analysis of the American Gut Project

AbstractBackgroundCesarean birth is associated with altered composition of the neonate's microbiota and with increased risk for obesity and other diseases later in life. The mechanisms of these associations, and whether cesarean birth is associated with an altered adult microbiota, are unknown.MethodsIn 1097 adult volunteers without diabetes, inflammatory bowel disease, or recent antibiotic use, fecal microbiome metrics were compared by history of cesarean birth (N=92) or appendectomy (N=115). Associations with potential confounders, microbiome alpha diversity, and individual microbial taxa were estimated by logistic regression. Permutation tests assessed differences in microbial composition (beta diversity) based on Jensen–Shannon divergence.FindingsCesarean birth history was associated with younger age; appendectomy with older age and higher body mass index. Neither was associated with fecal microbiome alpha diversity. Microbial composition at all taxonomic levels differed significantly with cesarean birth (P≤0.008) but not with appendectomy (P≥0.29). Relative abundance differed nominally for 17 taxa with cesarean birth and for 22 taxa with appendectomy, none of which was significant with adjustment for multiple comparisons.InterpretationAdults born by cesarean section appear to have a distinctly different composition of their fecal microbial population. Whether this distinction was acquired during birth, and whether it affects risk of disease during adulthood, are unknown.FundingSupported by the Intramural Research Program, National Cancer Institute, National Institutes of Health (Z01-CP-010214)

Immunologic markers of progression to acquired immunodeficiency syndrome are time-dependent and illness-specific

Krämer A, Biggar RJ, Hampl H, et al. Immunologic markers of progression to acquired immunodeficiency syndrome are time-dependent and illness-specific. American Journal of Epidemiology. 1992;136(1):71-80.Since prevalent cohorts may be biased by the duration of human immunodeficiency virus (HIV) infection (onset bias), it is useful to assess the potential predictive value of markers in incident cohorts of HIV-positive subjects for whom the date of seroconversion is known or can reliably be estimated. Of 131 homosexual men with HIV-1 seroconversion from New York City and Washington, DC, who were evaluated annually beginning in 1982, 60 developed acquired immunodeficiency syndrome (AIDS) by the end of 1989. The prognostic significance of immunologic markers (proportion of CD4+ T-lymphocytes, neopterin, ß2-microglobulin, serum interferon, and anti-p24 antibody) and of a virologic marker (HIV p24 antigen) was determined using measurements made at defined time intervals after the known or estimated date of HIV seroconversion. When measurements made 3 years after seroconversion were used, all markers except anti-p24 antibody were found to be significant estimators of AIDS risk in univariate analyses. In multivariate Cox regression modeling, the maximum information was obtained by including neopterin, interferon, and the CD4+ T-lymphocyte proportion. The predictive value of markers after HIV seroconversion could change considerably from one interval to another. Elevated levels of ß2-microglobulin and neopterin significantly predicted the development of Kaposi‘s sarcoma. These two markers were highly correlated (r=0. 74). The authors conclude that immunologic markers can be important for an HIV staging system for estimating prognosis and facilitating early therapeutic intervention in HIV-positive patients

Feasibility of self-collection of fecal specimens by randomly sampled women for health-related studies of the gut microbiome

BACKGROUND: The field of microbiome research is growing rapidly. We developed a method for self-collection of fecal specimens that can be used in population-based studies of the gut microbiome. We conducted a pilot study to test the feasibility of our methods among a random sample of healthy, postmenopausal women who are members of Kaiser Permanente Colorado (KPCO). We aimed to collect questionnaire data, fecal and urine specimens from 60 women, aged 55–69, who recently had a normal screening mammogram. We designed the study such that all questionnaire data and specimens could be collected at home. RESULTS: We mailed an invitation packet, consent form and opt-out postcard to 300 women, then recruited by telephone women who did not opt-out. Verbally consented women were mailed an enrollment package including a risk factor questionnaire, link to an online diet questionnaire, specimen collection kit, and instructions for collecting stool and urine. Specimens were shipped overnight to the biorepository. Of the 300 women mailed an invitation packet, 58 (19%) returned the opt-out postcard. Up to 3 attempts were made to telephone the remaining women, of whom 130 (43%) could not be contacted, 23 (8%) refused, and 12 (4%) were ineligible. Enrollment packages were mailed to 77 women, of whom 59 returned the risk factor questionnaire and specimens. We found no statistically significant differences between enrolled women and those who refused participation or could not be contacted. CONCLUSIONS: We demonstrated that a representative sample of women can be successfully recruited for a gut microbiome study; however, significant personal contact and carefully timed follow-up from the study personnel are required. The methods employed by our study could successfully be applied to analytic studies of a wide range of clinical conditions that have been postulated to be influenced by the gut microbial population

Urinary neopterin concentrations vs total neopterins for clinical utility

Fuchs D, Milstien S, Krämer A, et al. Urinary neopterin concentrations vs total neopterins for clinical utility. Clinical Chemistry. 1989;35(12):2305-2307.Neopterin measurements are especially useful as an early marker in (e.g.) allograft rejections and in patients infected with human immunodeficiency virus type 1 (HIV-1). An increased concentration of total neopterins (neopterin + dihydroneopterin) is also a significant marker in patients with HIV-1 infection. In this study we compared concentrations of neopterin and total neopterins in urine samples from 77 homosexual men with and 73 without established HIV-1 infection. HIV- 1-seropositive homosexual men had higher concentrations of neopterin and total neopterins (and 7,8-dihydroneopterin) in their urine than did those who were HIV-1-seronegative, and there was a close correlation between neopterin and total neopterins. Both neopterin variables correlated inversely with CD4 + T-cell counts and CD4 +/CD8 + T-cell ratios but not with CD8+ T-cell counts in the HIV-1-seropositive men. Our data indicate that measurements of neopterin and total neopterins are of almost equal potential for clinical diagnosis. However, when measuring total neopterins, which includes oxidation of 7,8- dihydroneopterin to neopterin, more strict requirements of sample collection and handling are necessary to avoid degradation of the 7,8- dihydro derivative

Risk of classical Kaposi sarcoma by plasma levels of Epstein-Barr virus antibodies, sCD26, sCD23 and sCD30

<p>Abstract</p> <p>Background</p> <p>To clarify the immunological alterations leading to classical Kaposi sarcoma (cKS) among people infected with KS-associated herpesvirus (KSHV).</p> <p>Methods</p> <p>In a population-based study of 119 cKS cases, 105 KSHV-seropositive controls, and 155 KSHV-seronegative controls, we quantified plasma soluble cluster of differentiation (sCD) levels and antibodies against Epstein-Barr virus nuclear antigen-1 (anti-EBNA-1) and viral capsid antigen (anti-VCA). Differences between groups in prevalence of low-tertile anti-EBNA-1 and high-tertile anti-VCA were compared by logistic regression. Continuous levels between groups and by presence of cKS co-factors among controls were compared by linear regression and Mann-Whitney-Wilcoxon methods.</p> <p>Results</p> <p>Comparisons of cKS cases to seropositive controls and of seropositive to seronegative controls revealed no significant differences. However, controls with known cKS cofactors (male sex, nonsmoking, diabetes and cortisone use) had significantly lower levels of anti-EBNA (<it>P </it>= 0.0001 - 0.07) and anti-VCA (<it>P </it>= 0.0001 - 0.03). Levels of sCD26 were significantly lower for male and non-smoking controls (<it>P</it>_adj≤ 0.03), and they were marginally lower with older age and cortisone use (<it>P</it>_adj≤ 0.09).</p> <p>Conclusions</p> <p>Anti-EBV and sCD26 levels were associated with cofactors for cKS, but they did not differ between cKS cases and matched controls. Novel approaches and broader panels of assays are needed to investigate immunological contributions to cKS.</p

Genetic Markers of IgG Influence The Outcome of Infection with Hepatitis C Virus

We examined the role that immunoglobulin GM and KM allotypes—genetic markers of γ and κ chains, respectively—play in the outcome of hepatitis C virus (HCV) infection in white Americans. A total of 119 persons who had cleared HCV and 111 with persistent HCV infection were genotyped for the presence of several GM and KM determinants. Persistent HCV infection was more than three times as likely (odds ratio, 3.50; P = .01) in subjects who were carriers of the GM3 allele than in those who were noncarriers. These results show that particular GM alleles may be important determinants of the outcome of HCV infection

KIR/HLA Pleiotropism: Protection against Both HIV and Opportunistic Infections

The compound genotype KIR3DS1/HLA-B Bw4-80I, which presumably favors natural killer cell activation, has been implicated in protection against HIV disease. We show that this genotype confers dual protection over the course of HIV disease; early direct containment of HIV viral load, and late specific defense against opportunistic infections, but not AIDS-related malignancies. The double protection of KIR3DS1/Bw4-80I in an etiologically complex disease such as AIDS, along with the disease specificity of its effects is conceptually novel and underscores the intricacy of host immunogenetics against HIV/AIDS

Hemophilic Siblings With Chronic Hepatitis C: Familial Aggregation of Spontaneous and Treatment-Related Viral Clearance

Hemophilic siblings provide a unique population to explore the natural history of chronic hepatitis C