• diet
• gut dysbiosis
• gut microbiota
• multiple sclerosis
• probiotics

• gut microbiota
• malnutrition
• obesity
• overweight
• secretory IgA
• underweight

• Humans
• Gastrointestinal Microbiome
• HIV Infections/microbiology
• HIV Infections/drug therapy
• Dysbiosis/microbiology
• Cardiovascular Diseases/microbiology

• This work was performed within the Irish Clinical Academic Training (ICAT) Programme, supported by the Wellcome Trust and the Health Research Board, the Health Service Executive, National Doctors Training and Planning and the Health and Social Care, Research and Development Division, Northern Ireland.

• HIV antiretroviral-therapy
• longitudinal studies
• microbiota dysbiosis

• Humans
• Gastrointestinal Microbiome/drug effects
• HIV Infections/drug therapy
• Longitudinal Studies
• Dysbiosis
• Anti-HIV Agents/therapeutic use
• Anti-Retroviral Agents/therapeutic use
• Cross-Sectional Studies

• D43 TW010543 FIC NIH HHS
• K43 TW011957 FIC NIH HHS
• R21 AI148033 NIAID NIH HHS
• D43 TW010350 FIC NIH HHS
• D43 TW001035 FIC NIH HHS

• Humans
• Fecal Microbiota Transplantation/methods
• Virus Diseases/therapy
• COVID-19/therapy
• Gastrointestinal Microbiome
• Hepatitis B/therapy
• HIV Infections/therapy
• HIV Infections/microbiology
• Clinical Trials as Topic
• Treatment Outcome
• Clostridium Infections/therapy
• Clostridium Infections/microbiology
• SARS-CoV-2

• host–pathogen interactions
• human microbiome
• infectious diseases
• microbiome-targeted therapies
• treatment approaches

• RGP2/343/44 Deanship of Scientific Research at King Khalid University

• Gut microbiome
• HIV-associated neurocognitive disorder
• Microbiome-gut-brain axis
• Neurodegenerative disease
• Neuroinflammation

• Humans
• Gastrointestinal Microbiome
• Neurodegenerative Diseases/pathology
• Neuroinflammatory Diseases
• HIV
• Quality of Life
• Neurocognitive Disorders/metabolism
• Neurocognitive Disorders/pathology
• Brain/pathology
• HIV Infections/complications

• AIDS
• HIV
• ITS
• Inflammatory factors
• Intestinal fungi

• Humans
• Acquired Immunodeficiency Syndrome
• HIV Infections
• Mycobiome
• CD8-Positive T-Lymphocytes
• Interleukin-4
• Cytokines
• Anti-Inflammatory Agents

• U1604287 National Natural Science Foundation and Henan Joint Fund
• 2019AZB009 Henan Province Traditional Chinese Medicine Science Research Special Project
• Henan Province Characteristic Backbone Discipline Traditional Chinese Medicine Discipline Construction Project

• Cancer
• Clostridium butyricum
• Gut
• HIV
• Inflammation

• Humans
• Interleukin-10
• Inflammasomes
• HIV-1/genetics
• HIV Infections/drug therapy
• HIV Infections/genetics
• CD4-Positive T-Lymphocytes
• Immunity, Innate/genetics
• Genes, Tumor Suppressor
• Gene Expression
• DNA
• Viral Load

• U19 AI096109 NIAID NIH HHS
• K23 GM112526 NIGMS NIH HHS
• UM1 AI126623 NIAID NIH HHS
• KL2 TR002317 NCATS NIH HHS
• P30 AI027757 NIAID NIH HHS
• National Institute of General Medical Sciences
• Division of Intramural Research, National Institute of Allergy and Infectious Diseases
• National Center for Advancing Translational Sciences
• amfAR, The Foundation for AIDS Research
• Bill and Melinda Gates Foundation

• COVID-19
• SARS-CoV-2
• gastrointestinal symptoms
• human gut microbiome
• microbial ecology
• non-hospitalized patients

• Animals
• Mice
• Mice, Inbred C57BL
• SARS-CoV-2
• COVID-19
• Microbiota
• Mammals

• K08 HL165106 NHLBI NIH HHS
• R01 DK114034 NIDDK NIH HHS
• R01 AT011117 NCCIH NIH HHS
• F31 AI164671 NIAID NIH HHS
• R01 HL122593 NHLBI NIH HHS
• R01 AR074500 NIAMS NIH HHS
• HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
• HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• HHS | NIH | National Center for Complementary and Integrative Health (NCCIH)
• HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Division of Intramural Research, National Institute of Allergy and Infectious Diseases (DIR, NIAID)

• Epidemiology
• gastrointestinal cancer
• global burden
• inflammation
• risk factors

• HIV infection
• bacterial strain diversity
• chronic inflammation
• cytokine producing capacity
• human gut microbiome

• Humans
• HIV
• Interleukin-10
• Interleukin-6
• Dysbiosis
• HIV Infections/drug therapy
• Cytokines

• European Research Council

• GALT
• HIV-1 pathogenesis
• HIV-1 reservoir
• Tfh
• Th17
• Treg
• comorbidities
• gut dysbiosis

• Humans
• HIV Infections/drug therapy
• HIV-1
• Intestinal Mucosa/pathology
• CD4-Positive T-Lymphocytes
• Inflammation
• Lymphoid Tissue

• HIV
• coinfection
• helminths
• immune response profiles
• inflammation

• HDID5149/KR/2021 South African Medical Research Council

• FMT
• gut dysbiosis
• probiotics
• viral pathogenesis
• γδ T cell

• P51 OD011104 NIH HHS
• R01 DK131930 NIDDK NIH HHS
• R33 AI136100 NIAID NIH HHS
• R56 DK131531 NIDDK NIH HHS

• Birth weight
• HIV infection
• Microbiome
• Microbiota
• Pregnancy

• T32 AI060537 NIAID NIH HHS

• HIV
• fecal microbiota transplantation
• intestinal microbiome

• Fecal Microbiota Transplantation/adverse effects
• Feces/microbiology
• HIV
• HIV Infections
• Humans
• Randomized Controlled Trials as Topic
• T-Lymphocytes
• Treatment Outcome

• HIV
• gut phage translocation
• homeostatis
• immune checkpoint protein
• microbial translocation
• plasma phage load

• Dietary Supplements
• Fatty Acids, Volatile/therapeutic use
• HIV Infections/complications
• HIV Infections/drug therapy
• Humans
• Inflammation
• Propionates/therapeutic use
• Prospective Studies
• Quality of Life

• Flexopharm Brain GmbH & Co. KG

The microbiota has been observed altered in autoimmune diseases, including idiopathic inflammatory myopathies (IIMs), and associated with different treatments. Low-dose IL-2 treatment emerges as a new option for active IIMs. This study aims to explore the role of low-dose IL-2 in regulating intestinal dysbiosis involved in the IIMs. In this study, 13 patients with active IIMs were enrolled and received 1 ×10⁶ IU of IL-2 subcutaneously every other day for 12 weeks plus standard care. The clinical response and immune response were assessed. Stool samples were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3–V4 region of the 16S rRNA gene and analyze their associations with clinical and immunological characteristics. Our study demonstrated that diversity of microbiota decreased remarkably in patients with IIMs, compared to healthy controls. The inflammatory-related bacteria, such as Prevotellaceae increased, while some butyrate-producing bacteria, such as Pseudobutyrivibrio, Lachnospiraceae, Roseburia, and Blautia, decreased significantly. The alteration associated with disease activities in patients with IIMs. After low-dose IL-2 treatment, 92.31% (12/13) of patients achieved IMACS DOI at week 12. Proportion of Treg cells significantly increased at week 12 compared with that in baseline (15.9% [7.73, 19.4%] vs. 9.89% [6.02, 11.8%], P = 0.015). Interestingly, certain butyrate-producing bacteria increase significantly after IL-2 treatment, like Lachnospiraceae, Pseudobutyrivibrio, etc., and are associated with a rise in L-Asparagine and L-Leucine. The effects of low-dose IL-2 on gut microbiota were more apparent in NOD mice. Together, the data presented demonstrated that low-dose IL-2 was effective in active IIMs and highlighted the potential for modifying the intestinal microbiomes of dysbiosis to treat IIMs.

• Animals
• Dermatomyositis/drug therapy
• Dysbiosis/drug therapy
• Dysbiosis/microbiology
• Gastrointestinal Microbiome/physiology
• Humans
• Interleukin-2
• Mice
• Mice, Inbred NOD
• Microbiota
• RNA, Ribosomal, 16S/genetics

• AIDS
• HIV
• Immune reconstitution
• Mucosal immunity
• Mucosal-associated invariant T cells

• HCV
• HIV
• HPV
• anal cancer
• microbiome

• Antiretroviral therapy
• Cytokines
• HIV
• Immunological responders
• Inflammation
• Microbiome-immunity axis
• Microbiota
• Short chain fatty acid
• Viremia

• Cross-Sectional Studies
• Gastrointestinal Microbiome
• HIV Infections/diagnosis
• HIV Infections/drug therapy
• HIV-1
• Humans
• Microbiota
• Viremia

• CD4+ T cells
• acquired immune deficiency syndrome
• gut-lung axis
• microbiome
• pneumocystis pneumonia

• Humans
• Pneumonia, Pneumocystis/diagnosis
• Pneumonia, Pneumocystis/microbiology
• Gastrointestinal Microbiome
• Acquired Immunodeficiency Syndrome/complications
• HIV Infections/complications
• RNA, Ribosomal, 16S/genetics
• Lung/microbiology
• Microbiota

• conjunctiva microbiota
• hiv infection
• antiretroviral therapy
• 16s rrna sequencing
• dysbiosis

• Adult
• Anti-Retroviral Agents/therapeutic use
• Antiretroviral Therapy, Highly Active/methods
• Bacteria/genetics
• Bacteria/metabolism
• Conjunctiva/microbiology
• Conjunctiva/pathology
• Cross-Sectional Studies
• DNA, Viral/analysis
• Female
• Follow-Up Studies
• Gastrointestinal Microbiome/physiology
• HIV
• HIV Infections/drug therapy
• HIV Infections/virology
• Humans
• Male
• Middle Aged
• RNA, Ribosomal, 16S/genetics
• RNA, Ribosomal, 16S/metabolism

CD4⁺ T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4⁺ T cell counts in HIV-infected individuals. However, the association between CD4⁺ T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4⁺ T cell counts < 500 cells/μL) from Yunnan Province, China, has not been previously investigated.

To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/μL group and CD4 count < 200 cells/μL group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8⁺ T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups.

Compared to INRs with CD4 count > 200 cells/μL, those with CD4 count < 200 cells/μL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/μL group than in the CD4 count > 200 cells/μL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4⁺ T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae.

Our study demonstrated that lower CD4⁺ T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4⁺ T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs.

The online version contains supplementary material available at 10.1186/s12879-021-06491-z.

• CD4+ T cell counts
• Cytokines
• Gut microbiota
• Immunological non-responders
• Ruminococcaceae

The investigation of the microbial populations of the human body, known as the microbiome, has led to a revolutionary field of science, and understanding of its impacts on human development and health. The majority of microbiome research to date has focussed on bacteria and other kingdoms of life, such as fungi. Trailing behind these is the interrogation of the gut viruses, specifically the phageome. Bacteriophages, viruses that infect bacterial hosts, are known to dictate the dynamics and diversity of bacterial populations in a number of ecosystems. However, the phageome of the human gut, while of apparent importance, remains an area of many unknowns. In this paper we discuss the role of bacteriophages within the human gut microbiome. We examine the methods used to study bacteriophage populations, how this evolved over time and what we now understand about the phageome. We review the phageome development in infancy, and factors that may influence phage populations in adult life. The role and action of the phageome is then discussed at both a biological-level, and in the broader context of human health and disease.

• bacteriophages
• biofilm
• diet
• disease
• gut microbiome
• isolation
• metagenomics
• phage

Multiple factors, such as immune disruption, prophylactic co-trimoxazole, and antiretroviral therapy, may influence the structure and function of the gut microbiome of children infected with HIV from birth. In order to understand whether HIV infection altered gut microbiome and to relate changes in microbiome structure and function to immune status, virological response and pediatric ART regimens, we characterized the gut microbiome of 87 HIV-infected and 82 non-exposed HIV-negative children from Yaounde, a cosmopolitan city in Cameroon. We found that children living with HIV had significantly lower alpha diversity in their gut microbiome and altered beta diversity that may not be related to CD4+ T cell count or viral load. There was an increased level of Akkermansia and Faecalibacterium genera and decreased level of Escherichia and other Gamma proteobacteria in children infected with HIV, among other differences. We noted an effect of ethnicity/geography on observed gut microbiome composition and that children on ritonavir-boosted protease inhibitor (PI/r)-based ART had gut microbiome composition that diverged more from HIV-negative controls compared to those on non-nucleoside reverse-transcriptase inhibitors-based ART. Further studies investigating the role of this altered gut microbiome in increased disease susceptibility are warranted for individuals who acquired HIV via mother-to-child transmission.

With the discovery of antiretroviral therapy, HIV-1 infection has transitioned into a manageable but chronic illness, which requires lifelong treatment. Nevertheless, complete eradication of the virus has still eluded us. This is partly due to the virus’s ability to remain in a dormant state in tissue reservoirs, ‘hidden’ from the host’s immune system. Also, the high mutation rate of HIV-1 results in escape mutations in response to many therapeutics. Regardless, the development of novel cures for HIV-1 continues to move forward with a range of approaches from immunotherapy to gene editing. However, to evaluate in vivo pathogenesis and the efficacy and safety of therapeutic approaches, a suitable animal model is necessary. To this end, the humanized mouse was developed by McCune in 1988 and has continued to be improved on over the past 30 years. Here, we review the variety of humanized mouse models that have been utilized through the years and describe their specific contribution in translating HIV-1 cure strategies to the clinic.

• BLT
• DRAG
• HIV-1 infection
• gene therapy
• humanized mice
• immunotherapy
• latency reversal
• viral latency

• acquired immune deficiency syndrome
• disease transmission
• human immunodeficiency virus
• intestinal mucosa
• microbiota

Background: We explored the long-term effects of cART on markers of gut damage, microbial translocation, and paired gut/blood microbiota composition, with a focus on the role exerted by different drug classes.

Methods: We enrolled 41 cART naïve HIV-infected subjects, undergoing blood and fecal sampling prior to cART (T0) and after 12 (T12) and 24 (T24) months of therapy. Fifteen HIV-uninfected individuals were enrolled as controls. We analyzed: (i) T-cell homeostasis (flow cytometry); (ii) microbial translocation (sCD14, EndoCab, 16S rDNA); (iii) intestinal permeability and damage markers (LAC/MAN, I-FABP, fecal calprotectin); (iv) plasma and fecal microbiota composition (alpha- and beta-diversity, relative abundance); (v) functional metagenome predictions (PICRUSt).

Results: Twelve and twenty four-month successful cART resulted in a rise in EndoCAb (p = 0.0001) and I-FABP (p = 0.039) vis-à-vis stable 16S rDNA, sCD14, calprotectin and LAC/MAN, along with reduced immune activation in the periphery. Furthermore, cART did not lead to substantial modifications of microbial composition in both plasma and feces and metabolic metagenome predictions. The stratification according to cART regimens revealed a feeble effect on microbiota composition in patients on NNRTI-based or INSTI-based regimens, but not PI-based regimens.

Conclusions: We hereby show that 24 months of viro-immunological effective cART, while containing peripheral hyperactivation, exerts only minor effects on the gastrointestinal tract. Persistent alteration of plasma markers indicative of gut structural and functional impairment seemingly parallels enduring fecal dysbiosis, irrespective of drug classes, with no effect on metabolic metagenome predictions.

• cART initiation
• dysbiosis
• gut health
• intestinal damage
• microbial translocation

• retrovirus
• clinical microbiology
• microbiome

• Adult
• Anti-HIV Agents/therapeutic use
• Dysbiosis/drug therapy
• Dysbiosis/microbiology
• Dysbiosis/virology
• Female
• Gastrointestinal Microbiome/drug effects
• HIV Infections/drug therapy
• HIV Infections/microbiology
• HIV Infections/virology
• HIV Seropositivity/drug therapy
• HIV Seropositivity/virology
• HIV-1/drug effects
• Humans
• Male
• Middle Aged
• Mouth/microbiology
• Reverse Transcriptase Inhibitors/therapeutic use

• Japan Agency for Medical Research and Development