Assessment of the microbiome during bacteriophage therapy in combination with systemic antibiotics to treat a case of staphylococcal device infection.

BACKGROUND: Infectious bacterial diseases exhibiting increasing resistance to antibiotics are a serious global health issue. Bacteriophage therapy is an anti-microbial alternative to treat patients with serious bacterial infections. However, the impacts to the host microbiome in response to clinical use of phage therapy are not well understood. RESULTS: Our paper demonstrates a largely unchanged microbiota profile during 4 weeks of phage therapy when added to systemic antibiotics in a single patient with Staphylococcus aureus device infection. Metabolomic analyses suggest potential indirect cascading ecological impacts to the host (skin) microbiome. We did not detect genomes of the three phages used to treat the patient in metagenomic samples taken from saliva, stool, and skin; however, phages were detected using endpoint-PCR in patient serum. CONCLUSION: Results from our proof-of-principal study supports the use of bacteriophages as a microbiome-sparing approach to treat bacterial infections. Video abstract.

Reduced Independence in Daily Living Is Associated with the Gut Microbiome in People with HIV and HCV.

Alterations in the gut microbiome are associated with neurocognition and related disorders, including in the context of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. However, the connection between the gut microbiome and cognitive decline, gauged by increased dependence in instrumental activities of daily living (IADL), remains largely unexplored in the context of these diseases. Here we characterized the gut microbiome using 16S rRNA amplicon sequencing and untargeted metabolomics with liquid chromatography-mass spectrometry from 347 people with HIV, HIV and HCV, or neither, all of whom underwent a comprehensive neuropsychiatric assessment. We observed that IADL-dependent and -independent HIV-monoinfected (HIV-positive [HIV+]/HCV-negative [HCV-]) and coinfected (HIV+/HCV+) individuals have distinct gut microbiomes. Moreover, we found that dependent individuals with HIV or HIV and HCV were enriched in Bacteroides These results may have implications for the characterization of cognitive decline, as well as the development of potential prevention and treatment strategies for individuals infected with HIV and/or HCV. Of particular interest is the possibility that dietary interventions that are known to modify the microbiome could be used to shift the microbiome toward more favorable states for preserving independence.IMPORTANCE The microbes in the gut and the chemicals they produce by metabolism have been linked to brain function. In earlier work, we showed that infection with two viruses, HIV and HCV, changed the gut microbes and metabolism in ways that were associated with a lifetime history of major depressive disorder. Here, we extend this analysis looking at a measurement of independence in daily living. We find that in individuals with HIV, whether or not they also have HCV, those who reported reduced independence were enriched in a genus of bacteria called Bacteroides This result is interesting because Bacteroides is strongly associated with diets low in carbohydrates and high in animal protein, suggesting that diet changes may help preserve independent living in people living long-term with HIV (although clinical intervention trials would be needed in order to confirm this).

Depression in Individuals Coinfected with HIV and HCV Is Associated with Systematic Differences in the Gut Microbiome and Metabolome.

Depression is influenced by the structure, diversity, and composition of the gut microbiome. Although depression has been described previously in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) monoinfections, and to a lesser extent in HIV-HCV coinfection, research on the interplay between depression and the gut microbiome in these disease states is limited. Here, we characterized the gut microbiome using 16S rRNA amplicon sequencing of fecal samples from 373 participants who underwent a comprehensive neuropsychiatric assessment and the gut metabolome on a subset of these participants using untargeted metabolomics with liquid chromatography-mass spectrometry. We observed that the gut microbiome and metabolome were distinct between HIV-positive and -negative individuals. HCV infection had a large association with the microbiome that was not confounded by drug use. Therefore, we classified the participants by HIV and HCV infection status (HIV-monoinfected, HIV-HCV coinfected, or uninfected). The three groups significantly differed in their gut microbiome (unweighted UniFrac distances) and metabolome (Bray-Curtis distances). Coinfected individuals also had lower alpha diversity. Within each of the three groups, we evaluated lifetime major depressive disorder (MDD) and current Beck Depression Inventory-II. We found that the gut microbiome differed between depression states only in coinfected individuals. Coinfected individuals with a lifetime history of MDD were enriched in primary and secondary bile acids, as well as taxa previously identified in people with MDD. Collectively, we observe persistent signatures associated with depression only in coinfected individuals, suggesting that HCV itself, or interactions between HCV and HIV, may drive HIV-related neuropsychiatric differences.IMPORTANCE The human gut microbiome influences depression. Differences between the microbiomes of HIV-infected and uninfected individuals have been described, but it is not known whether these are due to HIV itself, or to common HIV comorbidities such as HCV coinfection. Limited research has explored the influence of the microbiome on depression within these groups. Here, we characterized the microbial community and metabolome in the stools from 373 people, noting the presence of current or lifetime depression as well as their HIV and HCV infection status. Our findings provide additional evidence that individuals with HIV have different microbiomes which are further altered by HCV coinfection. In individuals coinfected with both HIV and HCV, we identified microbes and molecules that were associated with depression. These results suggest that the interplay of HIV and HCV and the gut microbiome may contribute to the HIV-associated neuropsychiatric problems.