Experimental bacterial dysbiosis with consequent immune alterations increase intrarectal SIV acquisition susceptibility

Ortiz, Alexandra M.; Baker, Phillip J.; Langner, Charlotte A.; Simpson, Jennifer; Stacy, Apollo; Flynn, Jacob K.; Starke, Carly E.; Vinton, Carol L.; Fennessey, Christine M.; Belkaid, Yasmine; Keele, Brandon F.; Brenchley, Jason M.

doi:10.1016/j.celrep.2023.112020

Cited by 5 publications

(4 citation statements)

References 71 publications

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“…Обнаружено, что микробиом толстой кишки и МТ могут взаимодействовать при регуляции липидного обмена [Pan et al, 2022]. МТ уменьшает качественный и количественный состав микробиома толстой кишки у мышей с ожирением, вызванным диетой с высоким содержанием жиров, в то же время МТ значительно увеличивает относительную численность Akkermansia, которые играют роль в снижении веса у людей с ожирением [Pan et al, 2022].…”

Section: мелатонин и микробиом толстой кишкиunclassified

“…При ВЗК хорошо изучены изменения количественного и качественного состава микробиома кишечника, видовое разнообразие варьирует в зависимости от варианта ВЗК: у пациентов с ЯК на фоне уменьшения Bacteroidota (Bacteroidetes) и Bacillota (Firmicutes) возрастает количество грамотрицательных Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli, Clostridium difficile), в то время как при БК сокращается представительство Clostridium spp., а повышение Escherichia coli выражено в большей степени, чем при ЯК [Jeon et al, 2022]. Bacteroidota (Bacteroidetes) составляют около 30% всех кишечных бактерий и могут рассматриваться как одна из основных биот грамотрицательных бактерий в кишечнике [Ortiz et al, 2023]. Они выделяют токсины, включая поверхностный липополисахарид (LPS), токсичные протеолитические пептиды и бета-амилоид (Aβ).…”

Section: Introductionunclassified

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Melatonin as a promising factor in correction of the intestinal microbiome in inflammatory bowel diseases

Osikov,

Grechishkin,

Shishkova

et al. 2023

Вест. ПГУ. Биол.

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Inflammatory bowel diseases (IBD) include ulcerative colitis and Crohn's disease. The etiology and pathogenesis of IBD remain unclear, the most common hypothesis being that an abnormal immune response against the gut microbiome is triggered by environmental factors in genetically predisposed individuals. The disadvantages of first-line therapy for IBD are the occurrence of side effects in more than 30% of patients. In this regard, the development of new safe drugs that act mainly locally is relevant. The aim of the work is to analyze current data on the mechanisms of action, effects on the intestinal microbiome of melatonin in the context of possible use in IBD. Melatonin (MT) is a biologically active substance, synthesized in the body from tryptophan, and realizes its effects through MT-dependent and MT-independent receptors located in the cell membrane and nucleus. MT is involved in the regulation of circadian rhythms, has antioxidant and immunomodulatory effects. In experimental modeling of IBD and in clinical conditions, MT reduces the severity of the inflammatory process in the wall of the colon by interrupting the processes of lipid peroxidation and inactivation of free radicals, as well as by acting through specific receptors on the function of blood cells of lymphoid organs. MT in IBD leads to a qualitative and quantitative change in the intestinal microbiome, elimination of signs of dysbiosis, an increase in the number of short-chain fatty acid producers - Actinomycetota (Actinobacteria) and a decrease in the number of bacteria that increase the permeability of the intestinal barrier - Bacteroidota (Bacteroidetes). Presumably, MT has a bacteriostatic effect by binding free iron and acting on the NF-kB and STAT1 signaling pathways, which may be a factor in the correction of colon dysbiosis in IBD. Data on the effect of MT on the composition of the intestinal microbiome are a prerequisite for further preclinical studies and the possible use of melatonin in IBD in clinical practice.

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Section: мелатонин и микробиом толстой кишкиunclassified

Section: Introductionunclassified

Melatonin as a promising factor in correction of the intestinal microbiome in inflammatory bowel diseases

Osikov,

Grechishkin,

Shishkova

et al. 2023

Вест. ПГУ. Биол.

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“…Several studies of rhesus macaques have found that the rectal microbiome composition affects SIV acquisition [62][63][64]. Prior work [65,66] has also shown that asymptomatic rectal STI is associated with HIV seroconversion even in the setting of routine screening and treatment, which suggests that ongoing mucosal inflammation associated with asymptomatic STI could increase susceptibility to HIV.…”

Section: Plos Pathogensmentioning

confidence: 99%

HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men

Doren

Smith

et al. 2023

PLoS Pathog

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Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18–29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.

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“…While repetitive vancomycin treatment maintained this dysbiotic microbiome and resulted in a significant reduction in the continuity of the epithelial barrier of the gut, surprisingly, there was no influence on canonical metrics of SIV disease progression [ 60 ] (Table 1 ). However, subsequent work demonstrated that vancomycin-induced dysbiosis was sufficient to increase the number of transmitted founder viruses after low-dose intrarectal SIV challenge in NHPs [ 61 ]. Another study in acutely SIV-infected macaques found that early treatment with rifaximin and sulfasalazine reduced microbial translocation and immune activation.…”

Section: Introductionmentioning

confidence: 99%

From dysbiosis to defense: harnessing the gut microbiome in HIV/SIV therapy

Brenchley,

Serrano-Villar

2024

Microbiome

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Background Although the microbiota has been extensively associated with HIV pathogenesis, the majority of studies, particularly those using omics techniques, are largely correlative and serve primarily as a basis for hypothesis generation. Furthermore, most have focused on characterizing the taxonomic composition of the bacterial component, often overlooking other levels of the microbiome. The intricate mechanisms by which the microbiota influences immune responses to HIV are still poorly understood. Interventional studies on gut microbiota provide a powerful tool to test the hypothesis of whether we can harness the microbiota to improve health outcomes in people with HIV. Results Here, we review the multifaceted role of the gut microbiome in HIV/SIV disease progression and its potential as a therapeutic target. We explore the complex interplay between gut microbial dysbiosis and systemic inflammation, highlighting the potential for microbiome-based therapeutics to open new avenues in HIV management. These include exploring the efficacy of probiotics, prebiotics, fecal microbiota transplantation, and targeted dietary modifications. We also address the challenges inherent in this research area, such as the difficulty in inducing long-lasting microbiome alterations and the complexities of study designs, including variations in probiotic strains, donor selection for FMT, antibiotic conditioning regimens, and the hurdles in translating findings into clinical practice. Finally, we speculate on future directions for this rapidly evolving field, emphasizing the need for a more granular understanding of microbiome-immune interactions, the development of personalized microbiome-based therapies, and the application of novel technologies to identify potential therapeutic agents. Conclusions Our review underscores the importance of the gut microbiome in HIV/SIV disease and its potential as a target for innovative therapeutic strategies.

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Experimental bacterial dysbiosis with consequent immune alterations increase intrarectal SIV acquisition susceptibility

Cited by 5 publications

References 71 publications

Melatonin as a promising factor in correction of the intestinal microbiome in inflammatory bowel diseases

Melatonin as a promising factor in correction of the intestinal microbiome in inflammatory bowel diseases

HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men

From dysbiosis to defense: harnessing the gut microbiome in HIV/SIV therapy

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