Microbial mismanagement: how inadequate treatments for vaginal dysbiosis drive the HIV epidemic in women

Gustin, Andrew T.; Cromarty, Ross; Schifanella, Luca; Klatt, Nichole R.

doi:10.1016/j.smim.2021.101482

Cited by 13 publications

(11 citation statements)

References 208 publications

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“…Taken together, our study and previous studies from others suggest that physiological levels of SCFAs can act as chemoattractants for immune cells and specifically for neutrophils [ 35 , 76 ], while pathological concentrations prevent neutrophil migration independently of age. This anti-chemotactic action could be a contributing factor to the described low presence of neutrophils in vaginal secretions from women with BV [ 11 , 37 , 77 ], although reduced neutrophil presence during BV has not been confirmed in all studies [ 10 , 63 ]. Importantly, while our in vitro model evaluated the individual effects of each SCFA, neutrophils in the genital tract would be exposed to a combination of SCFAs, and therefore, the overall result remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…The vaginal microbiota is a dynamic community of bacteria that works as a first-line defense against invading pathogens, along with the epithelial mucosal barrier and the immune mucosal response [ 8 , 9 , 10 ]. The vaginal microbiota, dominated by the Lactobacilli species that maintain high concentrations of lactic acid [ 11 ] and a low pH in the lower tract, is considered to be beneficial and reduce the risk of HIV acquisition [ 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Short-Chain Fatty Acids Impair Neutrophil Antiviral Function in an Age-Dependent Manner

Carrillo‐Salinas

Parthasarathy

Lara

et al. 2022

Cells

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Half of the people living with HIV are women. Younger women remain disproportionally affected in endemic areas, but infection rates in older women are rising worldwide. The vaginal microbiome influences genital inflammation and HIV infection risk. Multiple factors, including age, induce vaginal microbial alterations, characterized by high microbial diversity that generate high concentrations of short-chain fatty acids (SCFAs), known to modulate neutrophil function. However, how SCFAs may modulate innate anti-HIV protection by neutrophils is unknown. To investigate SCFA-mediated alterations of neutrophil function, blood neutrophils from younger and older women were treated with SCFAs (acetate, butyrate and propionate) at concentrations within the range reported during bacterial vaginosis, and phenotype, migration and anti-HIV responses were evaluated. SCFA induced phenotypical changes preferentially in neutrophils from older women. Butyrate decreased CD66b and increased CD16 and CD62L expression, indicating low activation and prolonged survival, while propionate increased CD54 and CXCR4 expression, indicating a mature aged phenotype. Furthermore, acetate and butyrate significantly inhibited neutrophil migration in vitro and specifically reduced α-defensin release in older women, molecules with anti-HIV activity. Following HIV stimulation, SCFA treatment delayed NET release and dampened chemokine secretion compared to untreated neutrophils in younger and older women. Our results demonstrate that SCFAs can impair neutrophil-mediated anti-HIV responses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Short-Chain Fatty Acids Impair Neutrophil Antiviral Function in an Age-Dependent Manner

Carrillo‐Salinas

Parthasarathy

Lara

et al. 2022

Cells

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“…Since there are increasing indications that vaginal bacteria can modify topical TFV efficacy ( 125 , 131 ), additional studies determining if a particular bacterial species or the diversity of bacterial communities as a whole are linked to decreased efficacy of new PrEP candidates are warranted. A rapid and precise diagnosis of vaginal dysbiosis and local inflammation, although challenging and not everywhere possible, will be critical in improving the efficacy of HIV prevention efforts in women and to improve public health policy ( 132 ). Furthermore, the effect of other non-bacterial components of the microbiome such as viruses and fungi on the efficacy of PrEP need to be investigated.…”

Section: Biological Factors Influencing Hiv Transmission and The Effi...mentioning

confidence: 99%

Women for science and science for women: Gaps, challenges and opportunities towards optimizing pre-exposure prophylaxis for HIV-1 prevention

et al. 2022

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Preventing new HIV infections remains a global challenge. Young women continue to bear a disproportionate burden of infection. Oral pre-exposure prophylaxis (PrEP), offers a novel women-initiated prevention technology and PrEP trials completed to date underscore the importance of their inclusion early in trials evaluating new HIV PrEP technologies. Data from completed topical and systemic PrEP trials highlight the role of gender specific physiological and social factors that impact PrEP uptake, adherence and efficacy. Here we review the past and current developments of HIV-1 prevention options for women with special focus on PrEP considering the diverse factors that can impact PrEP efficacy. Furthermore, we highlight the importance of inclusion of female scientists, clinicians, and community advocates in scientific efforts to further improve HIV prevention strategies.

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“…The copyright holder for this preprint this version posted February 26, 2022. ; https://doi.org/10.1101/2022.02.25.481906 doi: bioRxiv preprint by a pathogenic infection (or an ecological stressor) may even increase susceptibility of a host to disease (Boutin, Bernatchez, Audet, & Derome, 2013;Gustin, Cromarty, Schifanella, & Klatt, 2021;Hinderfeld & Simoes-Barbosa, 2020). Hence, an understanding of host-associated microbial community changes in response to infectious disease epidemics has implications in wildlife disease management in both terrestrial (Allender, Baker, Britton, & Kent, 2018;Denman et al, 2018;Woodhams et al, 2014) and aquatic (Luter et al, 2017;Meyer et al, 2019;Quintanilla et al, 2018;Vezzulli, Pezzati, Huete-Stauffer, Pruzzo, & Cerrano, 2013)} systems.…”

Section: Introductionmentioning

confidence: 99%

Infection by a eukaryotic gut parasite in wild Daphnia sp. associates with a distinct bacterial community

Rajarajan

Wolinska

Walser

et al. 2022

FEMS Microbiology Ecology

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Host-associated bacterial communities play an important role in host fitness and resistance to diseases. Yet, few studies have investigated tripartite interaction between a host, parasite and host-associated bacterial communities in natural settings. Here, we use 16S rRNA gene amplicon sequencing to compare gut- and body- bacterial communities of wild water fleas belonging to the Daphnia longispina complex, between uninfected hosts and those infected with the common and virulent eukaryotic gut parasite Caullerya mesnili (Family: Ichthyosporea). We report community-level changes in host-associated bacteria with the presence of the parasite infection; namely decreased alpha diversity and increased beta diversity at the site of infection, i.e. host gut (but not host body). We also report decreased abundance of bacterial taxa proposed elsewhere to be beneficial for the host, and an appearance of taxa specifically associated with infected hosts. Our study highlights the host-microbiota-infection link in a natural system and raises questions about the role of host-associated microbiota in natural disease epidemics as well as the functional roles of bacteria specifically associated with infected hosts.

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Microbial mismanagement: how inadequate treatments for vaginal dysbiosis drive the HIV epidemic in women

Cited by 13 publications

References 208 publications

Short-Chain Fatty Acids Impair Neutrophil Antiviral Function in an Age-Dependent Manner

Short-Chain Fatty Acids Impair Neutrophil Antiviral Function in an Age-Dependent Manner

Women for science and science for women: Gaps, challenges and opportunities towards optimizing pre-exposure prophylaxis for HIV-1 prevention

Infection by a eukaryotic gut parasite in wild Daphnia sp. associates with a distinct bacterial community

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