SUMMARY Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases. We show that the enteric virome is abnormal in CD and UC patients. In-depth analysis of preparations enriched for free virions in the intestine revealed that CD and UC were associated with a significant expansion of Caudovirales bacteriophages. The viromes of CD and UC patients were disease- and cohort-specific. Importantly, it did not appear that expansion and diversification of the enteric virome was secondary to changes in bacterial populations. These data support a model in which changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis. We conclude that the virome is a candidate for contributing to, or being a biomarker for, human inflammatory bowel disease and speculate that the enteric virome may play a role in other diseases.

SUMMARY Human immunodeficiency virus (HIV) infection is associated with increased intestinal translocation of microbial products and enteropathy as well as alterations in gut bacterial communities. However, whether the enteric virome contributes to this infection and resulting immunodeficiency remains unknown. We characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. Additionally, the enteric bacterial microbiome of patients with lower CD4 T counts exhibited reduced phylogenetic diversity and richness with specific bacteria showing differential abundance, including increases in Enterobacteriaceae, which have been associated with inflammation. Thus, immunodeficiency in progressive HIV infection is associated with alterations in the enteric virome and bacterial microbiome, which may contribute to AIDS-associated enteropathy and disease progression.

SUMMARY AIDS caused by simian immunodeficiency virus (SIV) infection is associated with gastrointestinal disease, systemic immune activation and, in cross sectional studies, changes in the enteric virome. Here we performed a longitudinal study of a vaccine cohort to define the natural history of changes in the fecal metagenome in SIV-infected monkeys. Matched rhesus macaques were either uninfected or intrarectally challenged with SIV, with a subset receiving the Ad26 vaccine, an adenovirus vector expressing the viral Env/Gag/Pol antigens. Progression of SIV infection to AIDS was associated with increased detection of potentially pathogenic viruses and bacterial enteropathogens. Specifically, adenoviruses were associated with an increased incidence of gastrointestinal disease and AIDS-related mortality. Viral and bacterial enteropathogens were largely absent from animals protected by the vaccine. These data suggest that the SIV-associated gastrointestinal disease is associated with the presence of both viral and bacterial enteropathogens and protection against SIV infection by vaccination prevents enteropathogen emergence.

Background Whether human immunodeficiency virus (HIV) infection impacts gut microbial α-diversity is controversial. We reanalyzed raw 16S ribosomal RNA (rRNA) gene sequences and metadata from published studies to examine α-diversity measures between HIV-uninfected (HIV–) and HIV-infected (HIV+) individuals. Methods We conducted a systematic review and individual level meta-analysis by searching Embase, Medline, and Scopus for original research studies (inception to 31 December 2017). Included studies reported 16S rRNA gene sequences of fecal samples from HIV+ patients. Raw sequence reads and metadata were obtained from public databases or from study authors. Raw reads were processed through standardized pipelines with use of a high-resolution taxonomic classifier. The χ2 test, paired t tests, and generalized linear mixed models were used to relate α-diversity measures and clinical metadata. Results Twenty-two studies were identified with 17 datasets available for analysis, yielding 1032 samples (311 HIV–, 721 HIV+). HIV status was associated with a decrease in measures of α-diversity (P < .001). However, in stratified analysis, HIV status was associated with decreased α-diversity only in women and in men who have sex with women (MSW) but not in men who have sex with men (MSM). In analyses limited to women and MSW, controlling for HIV status, women displayed increased α-diversity compared with MSW. Conclusions Our study suggests that HIV status, sexual risk category, and gender impact gut microbial community α-diversity. Future studies should consider MSM status in gut microbiome analyses.

N ucleic acid amplification testing (NAAT) for viral etiologies of central nervous system (CNS) infections provides rapid diagnosis for optimization of therapy (1, 2). However, this testing can be costly and may not always be used judiciously (3). In this era of cost containment, with a growing emphasis on the optimal use of diagnostic tests (4-8), we assessed ordering practices for viral NAAT with cerebrospinal fluid (CSF) specimens. Our objective was to develop criteria to reduce unnecessary testing.Herpes simplex virus 1 (HSV-1) is the most common treatable cause of viral encephalitis (9), while three of the most commonly identified causes of aseptic meningitis are herpes simplex virus 2 (HSV-2), varicella-zoster virus (VZV), and enteroviruses (EV) (10, 11). In addition, cytomegalovirus (CMV) infections of the CNS may be of clinical concern among immunocompromised individuals (12). NAAT has become the gold standard for diagnosis of most viral CNS infections (1, 2).Viral CSF NAAT has several important benefits. First, early diagnosis enables adequate administration of antiviral treatment for HSV-1/2, VZV, and CMV, if necessary. Second, while no targeted EV therapies currently exist, utilization of NAAT for EV diagnosis has been correlated with reductions in length of stay, ancillary testing, antibiotic utilization, and costs in pediatric populations (13, 14). However, utilization of viral NAAT assays in cases with low pretest probability may unnecessarily increase costs while decreasing the positive predictive value of the testing (13, 15). Several previous studies evaluated the implementation of laboratory screening criteria to reduce superfluous CSF NAAT for HSV-1/2 (16, 17). However, those studies were restricted to HSV-1/2 and had limited sample sizes.Herein we describe a retrospective study of nearly 11,000 CSF NAAT assays and we propose screening criteria for HSV-1/2, VZV, CMV, and EV testing. Using data from 2008 to 2012, we identified CSF characteristics with very high negative predictive values for HSV-1/2, VZV, CMV, and EV. We then retrospectively applied those screening criteria to CSF requests for a 1-year period (2013), to assess the cost savings and impact of the proposed algorithm. Finally, we describe the impact of implementation of the acceptance criteria described herein.(This work was presented in part at the 49th Annual Meeting of the Academy of Clinical Laboratory Physicians and Scientists, San Francisco, CA, May 30, 2014.) MATERIALS AND METHODSStudy overview. Barnes-Jewish Hospital (BJH) is an urban, adult, tertiary care hospital in St. Louis, MO. Data on all HSV-1/2, VZV, CMV, and EV NAAT studies ordered at BJH between January 1, 2008, and December 31, 2013, were obtained from the laboratory information system. Data on laboratory CSF characteristics and immune status were collected for all subjects with positive NAAT results and either twice as many randomly selected subjects with negative results (2008-2012 cohort) or 10% of all subjects with negative results (2013 cohort). Subjects wi...