HIV-associated gut microbial alterations are dependent on host and geographic context.

HIV-associated changes in intestinal microbiota are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. To better understand the impact of HIV on fecal microbiota globally, we compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana. We identify significant bacterial taxa alterations with both treated and untreated HIV infection with a high degree of uniqueness in each cohort. HIV-associated taxa alterations are also significantly different between populations that report men who have sex with men (MSM) behavior and non-MSM populations. Additionally, while we find that HIV infection is consistently associated with higher soluble markers of immune activation, most specific bacterial taxa associated with these markers in each region are not shared and none are shared across all three geographic locations in our study. Our findings demonstrate that HIV-associated changes in fecal microbiota are overall distinct among geographical locations and sexual behavior groups, although a small number of taxa shared between pairs of geographic locations warrant further investigation, highlighting the importance of considering host context to fully assess the impact of the gut microbiome on human health and disease.

Developing a pulse oximetry home monitoring protocol for patients suspected with COVID-19 after emergency department discharge.

OBJECTIVES: Patients with COVID-19 can present to the emergency department (ED) without immediate indication for admission, but with concern for decompensation. Clinical experience has demonstrated that critical illness may present later in the disease course and hypoxia is often the first indication of disease progression. The objectives of this study are to (a) assess feasibility and describe a protocol for ED-based outpatient pulse-oximetry monitoring with structured follow-up and (b) determine rates of ED return, hospitalisation and hypoxia among participants. METHODS: Prospective observational study of patients presenting to a single academic ED in Boston with suspected COVID-19. Eligible patients were adults being discharged from the ED with presumed COVID-19. Exclusion criteria included resting oxygen saturation <92%, ambulatory oxygen saturation <90%, heart rate >110 beats per minute or inability to use the device. Study personnel made scripted phone calls on postdischarge days 1, 3 and 7 to review the pulse-oximetry readings and to evaluate for decompensation. Return visit and admission information were collected via medical record and 28-day follow-up calls. RESULTS: 81 patients were enrolled of which 10 (12%) developed hypoxia after their initial discharge from the ED. Overall, 23 (28%) of the 81 patients returned to the ED at least once and 10 of those who returned (43%) were admitted. We successfully contacted 76/81 (94%) of subjects via phone at least once for follow-up assessment. DISCUSSION: Patients are eager and willing to participate in home monitoring systems and are comfortable with using technology, which will allow providers and health systems to extend our hospitals capabilities for tracking patient populations in times of crisis. CONCLUSIONS: It is feasible to implement an outpatient pulse-oximetry monitoring protocol to monitor patients discharged from the ED with confirmed or suspected COVID-19.

Cervicovaginal Microbiota and Reproductive Health: The Virtue of Simplicity.

Cervicovaginal microbiota play a critical role in women's health and reproductive outcomes. Despite being one of the simplest commensal bacterial communities in the human body, we are only beginning to appreciate its complex dynamic nature and important role in host immune modulation. In this review, we discuss the "optimal" cervicovaginal bacterial community composition, the impact of microbiota on gynecologic and obstetric outcomes, and the hurdles to developing a deeper mechanistic understanding of the function of the cervicovaginal microbiome. We then describe efforts to durably alter microbial composition in this compartment by promotion of Lactobacillus colonization with probiotics, modulation of vaginal pH, hormonal administration, and the eradication of pathogenic bacteria with antibiotics. Finally, we draw on lessons learned from the deeply investigated gut microbiome to suggest future avenues of research into host-pathogen interactions in the female genital tract.

HIV-associated changes in the enteric microbial community: potential role in loss of homeostasis and development of systemic inflammation.

PURPOSE OF REVIEW: Despite HIV therapy advances, average life expectancy in HIV-infected individuals on effective treatment is significantly decreased relative to uninfected persons, largely because of increased incidence of inflammation-related diseases, such as cardiovascular disease and renal dysfunction. The enteric microbial community could potentially cause this inflammation, as HIV-driven destruction of gastrointestinal CD4 T cells may disturb the microbiota-mucosal immune system balance, disrupting the stable gut microbiome and leading to further deleterious host outcomes. RECENT FINDINGS: Varied enteric microbiome changes have been reported during HIV infection, but unifying patterns have emerged. Community diversity is decreased, similar to pathologies such as inflammatory bowel disease, obesity, and Clostridium difficile infection. Many taxa frequently enriched in HIV-infected individuals, such as Enterobacteriaceae and Erysipelotrichaceae, have pathogenic potential, whereas depleted taxa, such as Bacteroidaceae and Ruminococcaceae, are more linked with anti-inflammatory properties and maintenance of gut homeostasis. The gut viral community in HIV has been found to contain a greater abundance of pathogenesis-associated Adenoviridae and Anelloviridae. These bacterial and viral changes correlate with increased systemic inflammatory markers, such as serum sCD14, sCD163, and IL-6. SUMMARY: Enteric microbial community changes may contribute to chronic HIV pathogenesis, but more investigation is necessary, especially in the developing world population with the greatest HIV burden (Video, Supplemental Digital Content 1, http://links.lww.com/COID/A15, which includes the authors' summary of the importance of the work).

Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome.

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.

Diet rapidly and reproducibly alters the human gut microbiome.

Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta.

Despite numerous examples of the effects of the human gastrointestinal microbiome on drug efficacy and toxicity, there is often an incomplete understanding of the underlying mechanisms. Here, we dissect the inactivation of the cardiac drug digoxin by the gut Actinobacterium Eggerthella lenta. Transcriptional profiling, comparative genomics, and culture-based assays revealed a cytochrome-encoding operon up-regulated by digoxin, inhibited by arginine, absent in nonmetabolizing E. lenta strains, and predictive of digoxin inactivation by the human gut microbiome. Pharmacokinetic studies using gnotobiotic mice revealed that dietary protein reduces the in vivo microbial metabolism of digoxin, with significant changes to drug concentration in the serum and urine. These results emphasize the importance of viewing pharmacology from the perspective of both our human and microbial genomes.