Search

The gut microbiome has coevolved with humans to aid in physiologic functions and prevent disease. An increasing prevalence of gut dysbiosis in modern society exists and has strong linkages to multiple disease processes common in the developed world. Mechanisms for microbiome-human interactions that impact host homeostasis include bacterial metabolite/toxin production, biofilm formation with mucous layer infiltration, and host immune system modulation. Most of this crosstalk occurs at the epithelial layer of the gut, and as such the role of these interactions in the induction of colorectal cancer—a highly prevalent disease globally and one undergoing significant epidemiologic shifts—is under increasing scrutiny. Although multiple individual gut bacteria have been hypothesized as possible driver organisms in the oncogenic process, no bacterium has been definitively identified as a causal agent of colorectal cancer, suggesting that host lifestyle factors, microbiome community interactions, and the mucosal and/or systemic immune response may play a critical role in the process. Recent evidence has emerged implicating the ubiquitous human pathogen Clostridioides difficile as a possible promoter of colorectal cancer through chronic toxin-mediated cellular changes. Although much remains to be defined regarding the natural history of infections caused by this pathogen and its potential for oncogenesis, it provides a strong model for the role of both individual bacteria and of the gut microbial community as a whole in the development of colorectal cancer. The gut microbiome can play a crucial role in the development and prevention of human cancers through a variety of individual bacterial and broader community mechanisms. Emerging evidence suggests that Clostridioides difficile could be an important contributor to this balance. [ABSTRACT FROM AUTHOR]

Opportunities for leadership in the specialty of infectious diseases (ID) have markedly increased over the last decade, including in newly recognized areas. Commensurate with the expansion of opportunities in ID, pathways to leadership positions within the Infectious Diseases Society of America (IDSA) are expanding as the Society seeks to advance the field for IDSA members. Acknowledging both the importance of diverse leaders to organizational success and shortfalls in diverse representation within IDSA leadership led to concentrated efforts to enhance transparency and opportunities for members to participate broadly in the work of IDSA. Herein, IDSA leaders reflect on their paths to IDSA leadership, hoping to help guide members seeking to partner with the Society. Features identified as important to individual success include mentorship, networking, participation in ID and IDSA volunteer experiences, passion for ID, and working with IDSA staff to advance the programs and initiatives of IDSA on behalf of members. [ABSTRACT FROM AUTHOR]

Opportunities for leadership in the specialty of infectious diseases (ID) have markedly increased over the last decade, including in newly recognized areas. Commensurate with the expansion of opportunities in ID, pathways to leadership positions within the Infectious Diseases Society of America (IDSA) are expanding as the Society seeks to advance the field for IDSA members. Acknowledging both the importance of diverse leaders to organizational success and shortfalls in diverse representation within IDSA leadership led to concentrated efforts to enhance transparency and opportunities for members to participate broadly in the work of IDSA. Herein, IDSA leaders reflect on their paths to IDSA leadership, hoping to help guide members seeking to partner with the Society. Features identified as important to individual success include mentorship, networking, participation in ID and IDSA volunteer experiences, passion for ID, and working with IDSA staff to advance the programs and initiatives of IDSA on behalf of members. [ABSTRACT FROM AUTHOR]

Obesity is a complex metabolic disease caused, in part, by the interaction between an individual's genetics, metabolism, and environment. Emerging evidence supports the role of gut microbiota in mediating the interaction between the host and environment by extracting energy from food otherwise indigestible by the host and producing metabolites and cytokines that affect host metabolism. Furthermore, gut microbial imbalance or dysbiosis has been shown in metabolic diseases including obesity, and recent studies are beginning to unravel the mechanisms involved. The gut microbiota affects host metabolism and obesity through several pathways involving gut barrier integrity, production of metabolites affecting satiety and insulin resistance, epigenetic factors, and metabolism of bile acids and subsequent changes in metabolic signaling. While the field of gut microbiome and its role in obesity is early in its stage of development, it holds a promising future in providing us with novel therapeutic targets that may restore the gut microbiome to a healthy state and help in the prevention and treatment of obesity. [ABSTRACT FROM AUTHOR]

In October 2018, the Infectious Diseases Society of America (IDSA) Board of Directors (BOD) decided to develop a 2019 IDSA Strategic Plan. The IDSA BOD has invested in strategic planning at regular intervals as part of an ongoing process to review and to renew the vision and direction of IDSA. Herein, the 2018–2019 strategic planning process and outcomes are described. The 2019 IDSA Strategic Plan presents 4 key initiatives: (1) optimize the development, dissemination, and adoption of timely and relevant ID guidance and guidelines that improve the outcomes of clinical care; (2) quantify, communicate, and advocate for the value of ID physicians to increase professional fulfillment and compensation; (3) facilitate the growth and development of the ID workforce to meet emerging scientific, clinical, and leadership needs; and (4) develop and position a new tool to serve as the leading US benchmark to measure and drive national progress on antimicrobial resistance. The BOD looks forward to developing, implementing, assessing, and advancing the 2019 IDSA Strategic Plan working with member volunteers, Society partners, and IDSA staff. [ABSTRACT FROM AUTHOR]

The article focuses on genotoxic gut bacteria which damage or mutate DNA are critical drivers of colorectal cancer (CRC) pathogenesis. Topics include considered the notable increase in early-onset CRC incidence highlights the urgency to discover responsible exogenous factors that are amenable to therapeutic intervention.

The authors identified a positive dose-response antibiotic-cancer association primarily confined to the proximal colon with an inverse association between antibiotic exposure and rectal cancer. Given that most people are exposed to more than 1 antibiotic class over time (7), the independent effect of antibiotic class might be best revealed by studying prescriptions of single antibiotic classes. The authors report that antibiotics with anti-aerobic activity (eg, quinolones, trimethoprim-sulfonamide) seemed to drive the increased proximal colon risk, whereas multiple antibiotic classes associated with diminished rectal cancer risk. [Extracted from the article]

The human body comprises fewer host cells than bacterial cells, most of which are obligate anaerobes residing in the gut. The symbiont Bacteroides fragilis constitutes a relatively small proportion (up to 1%-2%) of cultured fecal bacteria, but colonizes most humans. There are 2 classes of B. fragilis distinguished by their ability to secrete a zinc-dependent metalloprotease toxin, B. fragilis toxin (BFT). Strains that do not secrete BFT are nontoxigenic B. fragilis (NTBF), and those that do are called enterotoxigenic B. fragilis (ETBF). ETBF can induce clinical pathology, including inflammatory diarrhea, although asymptomatic colonization may be common. Intestinal inflammation is mediated by BFT, as yet the only known virulence factor of ETBF. Recent experimental evidence demonstrating that ETBF-driven colitis promotes colon tumorigenesis has generated interest in the potential contribution of ETBF to human colon carcinogenesis. Critical questions about the epidemiology of chronic, subclinical human colonization with ETBF and its impact on the biology of the colon need to be addressed. [ABSTRACT FROM AUTHOR]

The article discusses gut microbiota and how it acts as a critical determinant for immunotherapy responses. It cites a research by L. F. Mager published in this issue, which reveals how inosine produced by specific gut bacteria improves immune checkpoint inhibitor (ICI) efficacy in numerous mouse models. It mentions the need to understand the biosynthetic metabolite redundancy among bacterial species.

Abstract: Dr. Sydney Finegold is one of the most heralded leaders in the discovery, classification and scientific knowledge of anaerobic bacteria. On this occasion of his 90th birthday, this paper celebrates his lifetime of accomplishments and provides a perspective on the changes and growth in our understanding of one anaerobic species, Bacteroides fragilis. Over the last nearly 40 years, clinical and research data have fostered our current view that B. fragilis are essential symbiotes as well as, in some circumstances, pathogens with the capacity to induce both acute systemic and abdominal illnesses and possibly chronic colonic diseases. [Copyright &y& Elsevier]

The authors discuss the contribution of colon bacterial communities to the pathogenesis of colon cancer. They cite examples of infection-associated cancers that arise from chronic immune responses. They demonstrate in a study the capacity of a specific human colonic bacterium, enterotoxigenic Bacteroides fragilis, to induce colon tumors in multiple intestinal neoplasia. They also present a model of colon cancer induction by alpha-bugs.

Background. Diarrheal illnesses remain a leading cause of morbidity and mortality globally, with increasing recognition of long-term sequelae, including postinfectious irritable bowel syndrome and growth faltering, as well as cognitive deficits in children. Identification of specific etiologic agents is often lacking. In vitro and in vivo data suggest that enterotoxigenic Bacteroides fragilis (ETBF) may contribute to the burden of colonic inflammatory diarrheal disease. The study goal was to investigate the pathogenesis of ETBF diarrheal illnesses. Methods. We performed an observational study of children and adults with acute diarrheal illnesses in Dhaka, Bangladesh, from January 2004 through November 2005, to define the clinical presentation, intestinal inflammatory responses, and systemic and intestinal antibody responses to ETBF. Other enteric pathogens were also evaluated. Results. ETBF was identified to cause a clinical syndrome with marked abdominal pain and nonfebrile inflammatory diarrhea in both children (age, >1 year) and adults. Fecal leukocytes, lactoferrin, and proinflammatory cytokines (interleukin 8, tumor necrosis factor-α)—as well as B. fragilis toxin systemic antitoxin responses—increased rapidly in ETBF-infected patients. Evidence of intestinal inflammation often persisted for at least 3 weeks, despite antibiotic therapy. Conclusions. ETBF infection is a newly recognized cause of inflammatory diarrhea in children and adults. Future studies are needed to evaluate the role of ETBF in persistent colonic inflammation and other morbid sequelae of acute diarrheal disease. [ABSTRACT FROM AUTHOR]

Clostridium difficile disease is the major, known cause of nosocomial diarrhea and is an emerging cause of community-associated diarrhea. Recent outbreaks due to a strain of apparent increased virulence, BI/NAP1, and recognition of increasing metronidazole treatment failures as well as the morbidity associated with recurrent C. difficile disease have begun to spur studies to develop new therapies for C. difficile disease. Nitazoxanide, tolevamer, ramoplanin, and rifaximin are key agents being evaluated as new therapies for C. difficile disease. For now, vancomycin or metronidazole combined with discontinuation of antibiotics, when feasible, and expert infection control remain the mainstays of C. difficile disease management. [Copyright &y& Elsevier]

Abstract: Emerging data indicate that humans enjoy health through a productive collaboration with their colonizing flora, the majority of whom reside in the colon. This minireview provides a perspective on recent data and the exciting scientific challenges ahead. [Copyright &y& Elsevier]

Deals with a study which evaluated results in which enteric pathogens and their virulence factors appear to target the tight junctions (TJ) of epithelial cells. Common initial approach to investigating the impact of an enteric pathogen; Mechanisms by which TJ function or structure is altered by infection of epithelial cells.

Reports that studies of the impact of enteric pathogens and their virulence factors on the proteins comprising the tight junction and zonula adherens offer a novel approach to dissection of tight junctional complex regulation. Enteric pathogens that modify epithelial barrier function; Potential mechanisms used by enteric pathogens to modify tight junction function.

Data support that enterotoxigenic Bacteroides fragilis (ETBF) harbouring the Bacteroides fragilis toxin (bft) gene may promote colorectal tumourigenesis through the serrated neoplasia pathway. We hypothesized that ETBF may be enriched in colorectal carcinoma subtypes with high-level CpG island methylator phenotype (CIMP-high), BRAF mutation, and high-level microsatellite instability (MSI-high). Quantitative PCR assays were designed to quantify DNA amounts of Bacteroides fragilis , ETBF, and each bft gene isotype (bft-1 , bft-2 , or bft-3) in colorectal carcinomas in the Health Professionals Follow-up Study and Nurses' Health Study. We used multivariable-adjusted logistic regression models with the inverse probability weighting method. We documented 4476 colorectal cancer cases, including 1232 cases with available bacterial data. High DNA amounts of Bacteroides fragilis and ETBF were positively associated with BRAF mutation (p ≤ 0.0003), CIMP-high (p ≤ 0.0002), and MSI-high (p < 0.0001 and p = 0.01, respectively). Multivariable-adjusted odds ratios (with 95% confidence interval) for high Bacteroides fragilis were 1.40 (1.06–1.85) for CIMP-high and 2.14 (1.65–2.77) for MSI-high, but 1.02 (0.78–1.35) for BRAF mutation. Multivariable-adjusted odds ratios for high ETBF were 2.00 (1.16–3.45) for CIMP-high and 2.86 (1.64–5.00) for BRAF mutation, but 1.09 (0.67–1.76) for MSI-high. Neither Bacteroides fragilis nor ETBF was associated with colorectal cancer-specific or overall survival. The tissue abundance of Bacteroides fragilis is associated with CIMP-high and MSI-high, whereas ETBF abundance is associated with CIMP-high and BRAF mutation in colorectal carcinoma. Our findings support the aetiological relevance of Bacteroides fragilis and ETBF in the serrated neoplasia pathway. [ABSTRACT FROM AUTHOR]

Discusses the epidemiology of Cryptosporidium infection in children born in an urban slum in northeastern Brazil. Factors associated with Cryptosporidium-associated persistent diarrhea; Importance of copathogens in symptomatic cryptosporiodosis; Children at risk for symptomatic infection.

Studies whether tyrosine kinase activation is involved in the regulation of intestinal Cl- secretion using the human intestinal epithelial cell T84 line as a model Cl- secretory cell system. Cell culture and filter preparation; Cyclic nucleotide accumulation in intact cells; Intracellular Ca2+ measurement; Cellular transfection experiments.

Discusses enteric bacterial toxins' mechanisms of action and linkage to intestinal secretion. Criteria for establishing the pathogenicity of an enteric bacterial toxin; Potential mechanisms of intestinal secretion; Classification of enteric bacterial toxins; Functional classification of enteric bacterial toxins by genus and species; Intestinal pathophysiology.

Meta-analysis is a practical and powerful analytic tool that enables a unified statistical inference across the results from multiple studies. Notably, researchers often report the results on multiple related markers in each study (eg, various α-diversity indices in microbiome studies). However, univariate meta-analyses are limited to combining the results on a single common marker at a time, whereas existing multivariate meta-analyses are limited to the situations where marker-by-marker correlations are given in each study. Thus, here we introduce two meta-analysis methods, multi-marker meta-analysis (mMeta) and adaptive multi-marker meta-analysis (aMeta), to combine multiple studies throughout multiple related markers with no priori results on marker-by-marker correlations. mMeta is a statistical estimator for a pooled estimate and its SE across all the studies and markers, whereas aMeta is a statistical test based on the test statistic of the minimum P-value among marker-specific meta-analyses. mMeta conducts both effect estimation and hypothesis testing based on a weighted average of marker-specific pooled estimates while estimating marker-by-marker correlations non-parametrically via permutations, yet its power is only moderate. In contrast, aMeta closely approaches the highest power among marker-specific meta-analyses, yet it is limited to hypothesis testing. While their applications can be broader, we illustrate the use of mMeta and aMeta to combine microbiome studies throughout multiple α-diversity indices. We evaluate mMeta and aMeta in silico and apply them to real microbiome studies on the disparity in α-diversity by the status of human immunodeficiency virus (HIV) infection. The R package for mMeta and aMeta is freely available at https://github.com/hk1785/mMeta. [ABSTRACT FROM AUTHOR]

In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth. Rates of CRC are increasing in younger individuals, and CRC remains the second most frequent cause of cancer-related deaths globally. Hence, a more in-depth understanding of the role that gut microbes play in CRC is needed. Here, we review recent advances in understanding the impact of gut microbes on the genome and epigenome of CECs, as it relates to CRC. Overall, numerous studies in the past few years have definitively shown that gut microbes exert distinct impacts on DNA damage, DNA methylation, chromatin structure and non-coding RNA expression in CECs. Some of the genes and pathways that are altered by gut microbes relate to CRC development, particularly those involved in cell proliferation and WNT signaling. We need to implement more standardized analysis strategies, collate data from multiple studies, and utilize CRC mouse models to better assess these effects, understand their functional relevance, and leverage this information to improve patient care. [ABSTRACT FROM AUTHOR]

Physician-scientists, no matter their particular disease or research focus, within divisions of infectious diseases serve a number of key roles. Foremost, they promote scholarship and excellence in research endeavors with the potential for impact not only within their division or university but globally. These individuals also make important contributions to the training experiences of infectious diseases fellows and internal medicine residents, helping to foster an understanding of how evidence-based (or not) our patient care delivery actually is. Ongoing discussions between those focused on the clinical aspects of infectious diseases and those predominantly pursuing research questions enrich the scholarly environment for both physician groups and provides the foundation for translating the science to improved care for patients with infectious diseases. [ABSTRACT FROM AUTHOR]

Recent studies have raised interest in the possibility that dysbiosis of the gut microbiome (i.e., the communities of bacteria residing in the intestine) in HIV-infected patients could contribute to chronic immune activation, and, thus, to elevated mortality and increased risk of inflammation-related clinical diseases (e.g., stroke, cardiovascular disease, cancer, long-bone fractures, and renal dysfunction) found even in those on effective antiretroviral therapy. Yet, to date, a consistent pattern of HIV-associated dysbiosis has not been identified. What is becoming clear, however, is that status as a man who has sex with men (MSM) may profoundly impact the structure of the gut microbiota, and that this factor likely confounded many HIV-related intestinal microbiome studies. However, what factor associated with MSM status drives these gut microbiota-related changes is unclear, and what impact, if any, these changes may have on the health of MSM is unknown. In this review, we outline available data on changes in the structure of the gut microbiome in HIV, based on studies that controlled for MSM status. We then examine what is known regarding the gut microbiota in MSM, and consider possible implications for research and the health of this population. Lastly, we discuss knowledge gaps and needed future studies. [ABSTRACT FROM AUTHOR]

The human microbiota is a complex ecosystem of diverse microorganisms consisting of bacteria, viruses, and fungi residing predominantly in epidermal and mucosal habitats across the body, such as skin, oral cavity, lung, intestine and vagina. These symbiotic communities in health, or dysbiotic communities in disease, display tremendous interaction with the local environment and systemic responses, playing a critical role in the host’s nutrition, immunity, metabolism and diseases including cancers. While the profiling of normal microbiota in healthy populations is useful and necessary, more recent studies have focused on the microbiota associated with disease, particularly cancers. In this paper, we review current evidence on the role of the human microbiota in four cancer types (colorectal cancer, head and neck cancer, pancreatic cancer, and lung cancer) proposed as affected by both the oral and gut microbiota, and provide a perspective on current gaps in the knowledge of the microbiota and cancer. [ABSTRACT FROM AUTHOR]

Background: African Americans (AA) experience high levels of health disparities for several diseases, yet remain underrepresented in clinical trials and other types of research. The high ownership of smartphones among AA puts them in a unique position to be recruited into e-Health/m-Health interventions. Objective: This article is a systematic review of the participation of AA in e-Health/m-Health interventions, the diseases/health conditions targeted, and the recruitment and retention strategies used. Materials and Methods: A systematic review was done with PubMed, PsycINFO, Web of Science, EBSCOhost, and CINAHL databases, as well as hand searches of 14 journals. The search was restricted to studies conducted in the United States and that were published between January 2000 and June 2016. Twenty-three distinct search terms were used. Results: After removal of duplicates, 565 studies were screened and assessed for eligibility, and 56 met the inclusion criteria. Eight studies had exclusively AA participants. Eighty percent of the studies had female participants. Participants were recruited primarily from clinics/healthcare facilities. Forty-five percent of the studies provided monetary incentives. Only five studies addressed retention of participants. The diseases/health conditions that were studied included overweight/obesity, diabetes, physical activity, cardiovascular conditions, nutrition, prenatal health, and HIV. Conclusion: There was a low representation of AA in the studies in this review. Opportunities exist to engage AA in e-Health/m-Health research, but researchers must go beyond the traditional one-size-fits-all approach to determine what mixture of incentives and recruitment/retention strategies would work best for a particular health condition, population group, or community. [ABSTRACT FROM AUTHOR]

The gut microbiota has been hailed as an accessory organ, with functions critical to the host including dietary metabolic activities and assistance in the development of a proper functioning immune system. However, an aberrant microbiota (dysbiosis) may influence disease processes such as colorectal cancer. In this review, we discuss recent advances in our understanding of the contributions of the microbiota to prevention, initiation/progression, and treatment of colorectal cancer, with a major focus on biofilms and the antimicrobial and antitumoural immune response. [ABSTRACT FROM AUTHOR]

Human gut microbial species found to associate with clinical responses to immune checkpoint inhibitors (ICIs) are often tested in mice using fecal microbiota transfer (FMT), wherein tumor responses in recipient mice may recapitulate human responses to ICI treatment. However, many FMT studies have reported only limited methodological description, details of murine cohorts, and statistical methods. To investigate the reproducibility and robustness of gut microbial species that impact ICI responses, we performed human to germ-free mouse FMT using fecal samples from patients with non-small cell lung cancer who had a pathological response or nonresponse after neoadjuvant ICI treatment. R-FMT mice yielded greater anti-tumor responses in combination with anti-PD-L1 treatment compared to NR-FMT, although the magnitude varied depending on mouse cell line, sex, and individual experiment. Detailed investigation of post-FMT mouse microbiota using 16S rRNA amplicon sequencing, with models to classify and correct for biological variables, revealed a shared presence of the most highly abundant taxa between the human inocula and mice, though low abundance human taxa colonized mice more variably after FMT. Multiple Clostridium species also correlated with tumor outcome in individual anti-PD-L1-treated R-FMT mice. RNAseq analysis revealed differential expression of T and NK cell-related pathways in responding tumors, irrespective of FMT source, with enrichment of these cell types confirmed by immunohistochemistry. This study identifies several human gut microbial species that may play a role in clinical responses to ICIs and suggests attention to biological variables is needed to improve reproducibility and limit variability across experimental murine cohorts. [ABSTRACT FROM AUTHOR]

The Journal of Infectious Diseases expresses gratitude to its authors, reviewers, and readers for their support in 2023. The journal received 2121 manuscripts for peer review, an increase from the previous year. The editors acknowledge the important role of reviewers in improving and publishing scientifically sound studies. The journal introduced new article formats, such as "Viewpoints," and launched a Mentoring Pilot Program for junior faculty. In 2024, the journal plans to issue calls for papers on antimicrobial resistance, microbiome science, and vaccine science. They also aim to highlight topics important to junior investigators and career development in the field of infectious diseases. The journal will offer guaranteed reviews for Fellows of the Infectious Diseases Society of America and work to simplify submission requirements across their journals. They also plan to feature cover art and original art in their articles. The editors express their excitement for the progress made and their eagerness to consider new ideas with the support of their authors, reviewers, and readers. [Extracted from the article]

ABSTRACT BACKGROUND Given ever-reducing budgets of community and school substance use prevention programs, there is a call for identifying the first substance in the sequence leading to polydrug use. METHODS Examining data from a nationally representative sample of 2835 United States 12th graders, we sought to determine (1) the first substance adolescents use; (2) order in which adolescents progress through alcohol, tobacco, and marijuana use; and (3) impact of age of initial substance use on lifetime and frequency of illicit substance use. RESULTS Alcohol is the most commonly used substance, and the majority of polysubstance using respondents consumed alcohol prior to tobacco or marijuana initiation. Respondents initiating alcohol use in sixth grade reported significantly greater lifetime illicit substance use (M = 1.9, standard deviation [ SD] = 1.7, p < .001) and more frequent illicit substance use (M = 6.0, SD = 6.5, p < .001) than those initiating alcohol use in ninth grade or later. Overall, effect sizes for these differences were large (eta squared = 0.30 and 0.28, respectively). CONCLUSIONS Findings underscore the importance of screening for substance use, even among youth enrolled in elementary/middle school. In addition, school prevention programs should begin in elementary school (third grade) and target alcohol use. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) technology has advanced our understanding of the human microbiome by allowing for the discovery and characterization of unculturable microbes with prediction of their function. Key NGS methods include 16S rRNA gene sequencing, shotgun metagenomic sequencing, and RNA sequencing. The choice of which NGS methodology to pursue for a given purpose is often unclear for clinicians and researchers. In this Review, we describe the fundamentals of NGS, with a focus on 16S rRNA and shotgun metagenomic sequencing. We also discuss pros and cons of each methodology as well as important concepts in data variability, study design, and clinical metadata collection. We further present examples of how NGS studies of the human microbiome have advanced our understanding of human disease pathophysiology across diverse clinical contexts, including the development of diagnostics and therapeutics. Finally, we share insights as to how NGS might further be integrated into and advance microbiome research and clinical care in the coming years. [ABSTRACT FROM AUTHOR]

Noroviruses, recognized as the leading global cause of viral gastroenteritis and a major contributor to food-borne illness, present a growing challenge in health care and long-term care facilities. The virus spreads easily and by multiple routes. A visitor to a ward might initiate an outbreak by person-to-person contact, vomiting staff members or patients can disseminate the virus by airborne means, and contaminated surfaces, such as doorknobs and computer keyboards, can sustain an epidemic. In addition, although self-limited in healthy hosts, the virus can cause increased morbidity in more-vulnerable people. The GII.4 strain of the virus now dominates in multiple recent worldwide epidemics as well as in health care and long-term care facilities. Much like the influenza virus, norovirus appears to evolve by antigenic drift and evading the immune system, causing waves of global epidemics. Previous attempts at controlling outbreaks, both in the community and in closed facilities, provide guidance about the vigilance and action required by the health care community to diminish the clinical impact of norovirus infection. [ABSTRACT FROM AUTHOR]

The related genetic elements flanking the Bacteroides fragilis pathogenicity island (PAI) in enterotoxigenic B. fragilis (ETBF) 86-5443-2-2 and also present in pattern III nontoxigenic B. fragilis (NTBF) NCTC 9343 were defined as putative conjugative transposons (CTns), designated CTn86 and CTn9343, respectively (A. A. Franco, J. Bacteriol. 181:6623–6633, 2004). CTn86 and CTn9343 have the same basic structures except that their encoded transposases have low similarity and CTn9343 lacks the B. fragilis PAI and contains an extra 7-kb region not present in CTn86. In this study, using DNA hybridization and PCR analysis, we characterized the genetic element flanking the PAI in a collection of ETBF strains and the related genetic elements in a collection of NTBF pattern III strains. We found that in all 123 ETBF strains, the PAI is contained in a genetic element similar to CTn86. Of 73 pattern III strains, 26 (36%) present a genetic element similar to CTn9343, 38 (52%) present a genetic element similar to CTn9343 but lack the 7-kb region that is also absent in CTn86 (CTn9343-like element), and 9 (12%) present a genetic element similar to CTn86 but lacking the PAI (CTn86-like element). In addition to containing CTn86, ETBF strains can also contain CTn9343, CTn9343-like, or CTn86-like elements. CTn86, CTn9343, CTn86-like, and CTn9343-like elements were found exclusively in B. fragilis strains and predominantly in division I, cepA-positive strains. [ABSTRACT FROM AUTHOR]

In 1982, hemorrhagic colitis and hemolytic-uremic syndrome were linked to infection with Escherichia coli O157:H7, a serotype now classified as Shiga toxin-producing E. coli (STEC). Thereafter, hemorrhagic colitis and hemolytic-uremic syndrome associated with non-O157 STEC serogroups were reported, with the frequency of non-O157 STEC illness rivaling that of O157:H7 in certain geographic regions. In the United States, non-O157 E. coli may account for up to 20%-50% of all STEC infections. A high index of suspicion, paired with options to test for non-O157 STEC infection, are necessary for early recognition and appropriate treatment of these infections. Supportive care without the use of antibiotics is currently considered to be optimal treatment for all STEC infections. This commentary provides a perspective on the non-O157 STEC as human pathogens, how and when the clinician should approach the diagnosis of these organisms, and the challenges ahead. [ABSTRACT FROM AUTHOR]

G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35. Blocking GPR35 function in CECs using the GPR35 antagonist ML145, in conjunction with shRNA knock-down and CRISPRcas-mediated knock-out, resulted in reduced CEC-response to BFT as measured by E-cadherin cleavage, beta-arrestin recruitment and IL-8 secretion. Importantly, GPR35 is required for the rapid onset of ETBF-induced colitis in mouse models. GPR35-deficient mice showed reduced death and disease severity compared to wild-type C57Bl6 mice. Our data support a role for GPR35 in the CEC and mucosal response to BFT and underscore the importance of this molecule for sensing ETBF in the colon. Boleij et al. show that G protein-coupled receptor 35 (GPR35) regulates the responses to enterotoxigenic Bacteroides fragilis (ETBF) in colonic epithelial cells. They find that GPR35-deficiency nearly protected mice from ETBF-induced death, suggesting the importance of GPR35 in sensing ETBF in the colon. [ABSTRACT FROM AUTHOR]

Though women increasingly make up the majority of medical-school and other science graduates, they remain a minority in academic biomedical settings, where they are less likely to hold leadership positions or be awarded research funding. A major factor is the career breaks that women disproportionately take to see to familial duties. They experience a related, but overlooked, hurdle upon their return: they are often too old to be eligible for 'early-career researcher' grants and 'career-development' awards, which are stepping stones to leadership positions in many institutions and which determine the demographics of their hierarchies for decades to come. Though age limits are imposed to protect young applicants from more experienced seniors, they have an unintended side effect of excluding returning workers, still disproportionately women, from the running. In this joint effort by the European Society of Clinical Microbiology and Infectious Diseases, the Federation of European Microbiological Societies, the Infectious Disease Society of America, the International Society for Infectious Diseases and the Swiss Society for Infectious Diseases, we invited all European Congress of Clinical Microbiology and Infectious Diseases-affiliated medical societies and funding bodies to participate in a survey on current 'early-career' application restrictions and measures taken to provide protections for career breaks. The following simple consensus recommendations are geared to funding bodies, academic societies and other organizations for the fair handling of eligibility for early-career awards: 1. Apply a professional, not physiological, age limit to applicants. 2. State clearly in the award announcement that career breaks will be factored into applicants' evaluations such that: • Time absent is time extended : for every full-time equivalent of career break taken, the same full-time equivalent will be extended to the professional age limit. • Opportunity costs will also be taken into account : people who take career breaks risk additional opportunity costs, with work that they did before the career break often being forgotten or poorly documented, particularly in bibliometric accounting. Although there is no standardized metric to measure additional opportunity costs, organizations should (a) keep in mind their existence when judging applicants' submissions, and (b) note clearly in the award announcement that opportunity costs of career breaks are also taken into account. 3. State clearly that further considerations can be undertaken, using more individualized criteria that are specific to the applicant population and the award in question. The working group welcomes feedback so that these recommendations can be improved and updated as needed. [ABSTRACT FROM AUTHOR]