Glycan cross-feeding supports mutualism between Fusobacterium and the vaginal microbiota.

Women with bacterial vaginosis (BV), an imbalance of the vaginal microbiome, are more likely to be colonized by potential pathogens such as Fusobacterium nucleatum, a bacterium linked with intrauterine infection and preterm birth. However, the conditions and mechanisms supporting pathogen colonization during vaginal dysbiosis remain obscure. We demonstrate that sialidase activity, a diagnostic feature of BV, promoted F. nucleatum foraging and growth on mammalian sialoglycans, a nutrient resource that was otherwise inaccessible because of the lack of endogenous F. nucleatum sialidase. In mice with sialidase-producing vaginal microbiotas, mutant F. nucleatum unable to consume sialic acids was impaired in vaginal colonization. These experiments in mice also led to the discovery that F. nucleatum may also "give back" to the community by reinforcing sialidase activity, a biochemical feature of human dysbiosis. Using human vaginal bacterial communities, we show that F. nucleatum supported robust outgrowth of Gardnerella vaginalis, a major sialidase producer and one of the most abundant organisms in BV. These results illustrate that mutually beneficial relationships between vaginal bacteria support pathogen colonization and may help maintain features of dysbiosis. These findings challenge the simplistic dogma that the mere absence of "healthy" lactobacilli is the sole mechanism that creates a permissive environment for pathogens during vaginal dysbiosis. Given the ubiquity of F. nucleatum in the human mouth, these studies also suggest a possible mechanism underlying links between vaginal dysbiosis and oral sex.

Cumulative Encouragement to Diet From Adolescence to Adulthood: Longitudinal Associations With Health, Psychosocial Well-Being, and Romantic Relationships.

PURPOSE: The aim of the study was to identify whether parent encouragement to diet as an adolescent predicts subsequent encouragement to diet from significant others/romantic partners as an adult and examine longitudinal associations between cumulative encouragement to diet from close relationships (i.e., parent and significant other) and later weight, weight-related, and psychosocial well-being outcomes in adulthood. METHODS: Data from Project EAT I-IV, a 15-year longitudinal population-based study of socioeconomically and racially/ethnically diverse adolescents followed into adulthood (n = 1,116; mean age = 31.1 years; 61% female), were used for this study. Surveys and anthropometric measures were completed at school by adolescents in 1998-1999, and follow-up mailed and online surveys were completed at approximately 5-year intervals between 2003 and 2016. RESULTS: Adolescents who experienced encouragement to diet from their parents were more likely to have a significant other as an adult who also encouraged them to diet. In addition, there was a significant (p < .05) cumulative effect of encouragement to diet, such that experiencing more encouragement to diet from both a parent(s) and significant other was associated with higher weight status, more unhealthy weight-control behaviors (e.g., dieting, binge eating, and unhealthy weight control behaviors), and lower psychosocial well-being (e.g., lower body satisfaction and self-esteem and higher depressive symptoms) as a young adult. CONCLUSIONS: Encouragement to diet tracked from one close relationship to another and had a cumulative effect on adult weight, weight-related, and psychosocial well-being outcomes. Future interventions, clinical work, and research should be aware of these patterns and cumulative effects of encouragement to diet to target key relationships to reduce these harmful interpersonal patterns.

Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant.

Antibiotic treatment can deplete the commensal bacteria of a patient's gut microbiota and, paradoxically, increase their risk of subsequent infections. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotic administration is essential for optimal clinical outcomes but significantly disrupts intestinal microbiota diversity, leading to loss of many beneficial microbes. Although gut microbiota diversity loss during allo-HSCT is associated with increased mortality, approaches to reestablish depleted commensal bacteria have yet to be developed. We have initiated a randomized, controlled clinical trial of autologous fecal microbiota transplantation (auto-FMT) versus no intervention and have analyzed the intestinal microbiota profiles of 25 allo-HSCT patients (14 who received auto-FMT treatment and 11 control patients who did not). Changes in gut microbiota diversity and composition revealed that the auto-FMT intervention boosted microbial diversity and reestablished the intestinal microbiota composition that the patient had before antibiotic treatment and allo-HSCT. These results demonstrate the potential for fecal sample banking and posttreatment remediation of a patient's gut microbiota after microbiota-depleting antibiotic treatment during allo-HSCT.

Peeling the onion: the outer layers of Cryptococcus neoformans.

Cryptococcus neoformans is an opportunistic fungal pathogen that is ubiquitous in the environment. It causes a deadly meningitis that is responsible for over 180,000 deaths worldwide each year, including 15% of all AIDS-related deaths. The high mortality rates for this infection, even with treatment, suggest a need for improved therapy. Unique characteristics of C. neoformans may suggest directions for drug discovery. These include features of three structures that surround the cell: the plasma membrane, the cell wall around it, and the outermost polysaccharide capsule. We review current knowledge of the fundamental biology of these fascinating structures and highlight open questions in the field, with the goal of stimulating further investigation that will advance basic knowledge and human health.

Peeling the onion: the outer layers of Cryptococcus neoformans

Cryptococcus neoformans is an opportunistic fungal pathogen that is ubiquitous in the environment. It causes a deadly meningitis that is responsible for over 180,000 deaths worldwide each year, including 15% of all AIDS-related deaths. The high mortality rates for this infection, even with treatment, suggest a need for improved therapy. Unique characteristics of C. neoformans may suggest directions for drug discovery. These include features of three structures that surround the cell: the plasma membrane, the cell wall around it, and the outermost polysaccharide capsule. We review current knowledge of the fundamental biology of these fascinating structures and highlight open questions in the field, with the goal of stimulating further investigation that will advance basic knowledge and human health.

Protective Factors in the Intestinal Microbiome Against Clostridium difficile Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.

Background: Clostridium difficile infection (CDI) is a frequent complication in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), who receive intensive treatments that significantly disrupt the intestinal microbiota. In this study, we examined the microbiota composition of allo-HSCT recipients to identify bacterial colonizers that confer protection against CDI after engraftment. Methods: Feces collected from adult recipients allo-HSCT at engraftment were analyzed; 16S ribosomal RNA genes were sequenced and analyzed from each sample. Bacterial taxa with protective effects against development of CDI were identified by means of linear discriminant analysis effect size analysis and then further assessed with clinical predictors of CDI using survival analysis. Results: A total of 234 allo-HSCT recipients were studied; postengraftment CDI developed in 53 (22.6%). Within the composition of the microbiota, the presence of 3 distinct bacterial taxa was correlated with protection against CDI: Bacteroidetes, Lachnospiraceae, and Ruminococcaceae. Colonization with these groups at engraftment was associated with a 60% lower risk of CDI, independent of clinical factors. Conclusions: Colonization with these 3 bacterial groups is associated with a lower risk of CDI. These groups have been shown to be vital components of the intestinal microbiota. Targeted efforts to maintain them may help minimize the risk of CDI in this at-risk population.

Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium.

Antibiotic-mediated microbiota destruction and the consequent loss of colonization resistance can result in intestinal domination with vancomycin-resistant Enterococcus (VRE), leading to bloodstream infection in hospitalized patients. Clearance of VRE remains a challenging goal that, if achieved, would reduce systemic VRE infections and patient-to-patient transmission. Although obligate anaerobic commensal bacteria have been associated with colonization resistance to VRE, the specific bacterial species involved remain undefined. Herein, we demonstrate that a precisely defined consortium of commensal bacteria containing the Clostridium cluster XIVa species Blautia producta and Clostridium bolteae restores colonization resistance against VRE and clears VRE from the intestines of mice. While C. bolteae did not directly mediate VRE clearance, it enabled intestinal colonization with B. producta, which directly inhibited VRE growth. These findings suggest that therapeutic or prophylactic administration of defined bacterial consortia to individuals with compromised microbiota composition may reduce inter-patient transmission and intra-patient dissemination of highly antibiotic-resistant pathogens.

Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae.

Antibiotic resistance among enterococci and γ-proteobacteria is an increasing problem in healthcare settings. Dense colonization of the gut by antibiotic-resistant bacteria facilitates their spread between patients and also leads to bloodstream and other systemic infections. Antibiotic-mediated destruction of the intestinal microbiota and consequent loss of colonization resistance are critical factors leading to persistence and spread of antibiotic-resistant bacteria. The mechanisms underlying microbiota-mediated colonization resistance remain incompletely defined and are likely distinct for different antibiotic-resistant bacterial species. It is unclear whether enterococci or γ-proteobacteria, upon expanding to high density in the gut, confer colonization resistance against competing bacterial species. Herein, we demonstrate that dense intestinal colonization with vancomycin-resistant Enterococcus faecium (VRE) does not reduce in vivo growth of carbapenem-resistant Klebsiella pneumoniae. Reciprocally, K. pneumoniae does not impair intestinal colonization by VRE. In contrast, transplantation of a diverse fecal microbiota eliminates both VRE and K. pneumoniae from the gut. Fluorescence in situ hybridization demonstrates that VRE and K. pneumoniae localize to the same regions in the colon but differ with respect to stimulation and invasion of the colonic mucus layer. While VRE and K. pneumoniae occupy the same three-dimensional space within the gut lumen, their independent growth and persistence in the gut suggests that they reside in distinct niches that satisfy their specific in vivo metabolic needs.

Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease.

The relationship between intestinal microbiota composition and acute graft-versus-host disease (GVHD) after allogeneic blood/marrow transplantation (allo-BMT) is not well understood. Intestinal bacteria have long been thought to contribute to GVHD pathophysiology, but recent animal studies in nontransplant settings have found that anti-inflammatory effects are mediated by certain subpopulations of intestinal commensals. Hypothesizing that a more nuanced relationship may exist between the intestinal bacteria and GVHD, we evaluated the fecal bacterial composition of 64 patients 12 days after BMT. We found that increased bacterial diversity was associated with reduced GVHD-related mortality. Furthermore, harboring increased amounts of bacteria belonging to the genus Blautia was associated with reduced GVHD lethality in this cohort and was confirmed in another independent cohort of 51 patients from the same institution. Blautia abundance was also associated with improved overall survival. We evaluated the abundance of Blautia with respect to clinical factors and found that loss of Blautia was associated with treatment with antibiotics that inhibit anaerobic bacteria and receiving total parenteral nutrition for longer durations. We conclude that increased abundance of commensal bacteria belonging to the Blautia genus is associated with reduced lethal GVHD and improved overall survival.

Loss of Microbiota-Mediated Colonization Resistance to Clostridium difficile Infection With Oral Vancomycin Compared With Metronidazole.

Antibiotic administration disrupts the intestinal microbiota, increasing susceptibility to pathogens such as Clostridium difficile. Metronidazole or oral vancomycin can cure C. difficile infection, and administration of these agents to prevent C. difficile infection in high-risk patients, although not sanctioned by Infectious Disease Society of America guidelines, has been considered. The relative impacts of metronidazole and vancomycin on the intestinal microbiota and colonization resistance are unknown. We investigated the effect of brief treatment with metronidazole and/or oral vancomycin on susceptibility to C. difficile, vancomycin-resistant Enterococcus, carbapenem-resistant Klebsiella pneumoniae, and Escherichia coli infection in mice. Although metronidazole resulted in transient loss of colonization resistance, oral vancomycin markedly disrupted the microbiota, leading to prolonged loss of colonization resistance to C. difficile infection and dense colonization by vancomycin-resistant Enterococcus, K. pneumoniae, and E. coli. Our results demonstrate that vancomycin, and to a lesser extent metronidazole, are associated with marked intestinal microbiota destruction and greater risk of colonization by nosocomial pathogens.