Table 1 Summarizing Microbiota in HIV Table

Ellis et al. 2011 [33]

Kinetic (real time) quantitative-PCR of the 16S rRNA gene

12 HIV positive individuals, 5 seronegative individuals.

• No significant difference in the total quantity of 16S rRNA gene expression between HIV positive and seronegative individuals.

• A greater proportion of gram-negative bacteria, order Enterobacteriales was seen in HIV positive individuals compared with seronegative controls.

• The proportions of Enterobacteriales and Bacteroidales correlated with duodenal CD4+ T-cell depletion and peripheral CD8+ T-cell activation, respectively.

Vujkovic-Cvijin et al. 2013 [32]

Microarray of 16S rRNA gene

22 HIV positive individuals (6 viremic untreated, 16 on HAART), 9 seronegative individuals

• Dysbiotic mucosal-adherent microbiota. Enrichment of Proteobacteria and depletion of Bacteroidia in HIV infected individuals.

• Dysbiosis in individuals on HAART was correlated with the kynurenine pathway of tryptophan catabolism and plasma concentrations of IL-6

Lozupone et al. 2013 [27]

V4 region of 16S rRNA gene

22 chronic HIV infected individuals (with or without ART), 3 recently infected HIV positive individuals, 13 HIV seronegative individuals

• Recently infected individuals have a microbiota that differs only slightly from the microbiota of uninfected individuals.

• Short-term ART did not restore the microbiota to its uninfected composition.

• Increase abundances of Prevotellaceae, Erysipelotrichaceae, Veillonellaceae, Clostridium cluster XIII and the genus Desulfovibrio in chronically untreated individuals compared to HIV seronegative individuals.

• HIV seronegative individuals had increased abundance of Bacteroidaceae, Rikenellaceae, and Porphyromonadaceae.

McHardy et al. 2013 [39]

V4 region of 16S rRNA gene, in-silico metagenomics

20 HIV seronegative individuals, 20 HIV positive individuals on ART, 20 HIV positive individuals not on ART.

• Depletion of specific genera (such as Lachnospira, and Eubacterium,) and enrichment of other genera (such as Porphyromonas and Anaerococcus) in HIV positive individuals not on ART.

• HIV positive individuals on ART showed similar trends but to a lesser extent.

• Differences in attributed functionality were found between HIV positive individuals not receiving ART and healthy controls (eg. amino acid metabolism and vitamin biosynthesis).

Pérez-Santiago et al. 2013 [35]

V6 region of 16S rRNA gene

13 HIV positive individuals (before and during ART)

• Enrichment of Lactobacillales in HIV infected individuals before ART was associated with lower viral loads, higher CD4 T cell concentrations and lower markers of microbial translocation.

• Enrichment of Lactobacillales in HIV infected individuals after ART initiation was associated with lower translocation, lower systemic immune activation and higher CD4 T cell concentrations

Mutlu et al. 2014 [29]

16S rRNA gene

21 HIV positive individuals, 22 seronegative individuals.

• Reduced alpha diversity in the terminal ileum and colon were observed in HIV infection.

• Bacteria that increased in the HIV positive group are potentially pathogenic in other disease states.

• Higher diversity between microbiota samples in the HIV positive group compared with the seronegative group.

• A significant increase in Brachyspira, Campylobacter, Catenibacterium, Escherichia, Mogibacterium, Prevotella, and Ralstonia was observed in the HIV positive group.

• An increase in Akkermansia, Bacteroides, Blautia, Coprococcus, Dialister, Dorea, Faecalibacterium, Lachnospira, Roseburia, Ruminococcus, Odoribacter, Oscillospira was observed in the seronegative individuals group.

Lozupone et al. 2014 [24]

V4 region of 16S rRNA gene

40 HIV positive individuals (of them 28 on ART), 15 HIV seronegative individuals.

• The microbiota composition of individuals on ART was more similar to that of individuals with untreated HIV infection than seronegative individuals.

• Bacteroides and Odoribacter genera and Parabacteroides distasonis decrease with HIV infection, remain at low abundances in most individuals on ART.

• Prevotella genus, the Paraprevotellaceae family, and Eubacterium biforme increase with HIV infection, abundance varies in individuals undergoing ART (do not reach typical low levels of HIV-negative individuals).

• Peptococcus genus increased in untreated HIV infected individuals and decreases with ART.

• Desulfovibrio and Catenibacterium genera increase in untreated HIV infected individuals, while in individuals on ART they trended back to levels seen in HIV seronegative individuals.

Dillon et al. 2014 [28]

V4 region of 16S rRNA gene

18 untreated HIV positive individuals, 14 seronegative individuals

• Increased abundance of Proteobacteria and decreased abundance of Firmicutes in colon biopsies of HIV infected individuals compared with seronegative individuals.

• Within the Proteobacteria phylum, an increase in Brucellaceae, Xanthomonadaceae and Moraxellaceae and a decrease in Rhodospirillaceae was observed in HIV infected individuals.

• Within the Bacteroidetes phylum, an increase in Prevotellaceae and a decrease in Bacteroidaceae, Prophyromonadaceae and Rikenellaceae was observed HIV positive individuals.

• Within the Firmicutes phylum, Lachnospiraceae, Christensenellaceae and Ruminococcaceae were decreased in HIV-infected patients.

• The increased abundance in Proteobacteria seen in mucosal samples of HIV positive individuals, was not observed in fecal aspirates or rectal swabs.

• The decrease in mucosal Firmicutes in HIV infected individuals was observed in fecal aspirates, but not in stool samples.

• Trends seen in mucosal abundances of Proteobacteria and Firmicutes families and genera were not consistent in stool samples and fecal aspirates.

Nowak et al. 2015 [26]

V3-V4 region of 16S rRNA gene

31 HIV positive individuals (28 viremic, 3 elite controllers), 9 HIV seronegative individuals

• Decreased alpha diversity in untreated HIV infected patients.

• A further decrease in alpha diversity following ART.

• Prevotella genus significantly reduced during ART in HIV positive individuals.

• Higher relative abundance of Bacteroidetes in elite controllers compared to viremic patients.

• Increased abundance of Actinobacteria and Proteobacteria in viremic patients compared to elite controllers.

• Elite controllers did not differ significantly from seronegative controls at the phylum level.

• Increased relative abundance of Lactobacillus in viremic patients compared to seronegative individuals.

• Lachnobacterium, Faecalibacterium, and Haemophilus were significantly reduced in viremic patients compared to seronegative individuals.

Vázquez-Castellanos et al. 2015 [37]

V1, V2, V3 regions of 16S rRNA gene, whole genome shotgun sequencing

15 HIV positive individuals on ART, 15 seronegative individuals

• Healthy subjects cluster separately from positive subjects based on 16S rRNA sequencing.

• Enrichment in Prevotella and Succinivibrio in the microbiota of HIV positive individuals.

• Seronegative control individuals presented with microbiota enriched with Bacteroides and Faecalibacterium and generally had a more diverse composition.

• 12 KEGG pathways found to be enriched in the HIV positive subjects, specifically “ribosome” and “LPS biosynthesis” pathways being the most discriminative.

• 23 KEGG pathways found to be enriched in seronegative control, “starch and sucrose metabolism” and “glycolysis/gluconeogenesis” being the most discriminative.

Dinh et al. 2015 [23]

V3-V5 region of 16S rRNA gene

21 HIV positive individuals on ART, 16 seronegative individuals

• Greater abundance of Proteobacteria in HIV positive individuals compared to controls.

• Enrichment in Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae in the Proteobacteria phylum in HIV positive individuals compared to controls.

• Enrichement in Erysipelotrichi, Erysipelotrichales, and Erysipelotrichaceae in the Firmicutes phylum in HIV positive individuals compared to controls.

• Enrichement in Barnesiella and reduction in Rikenellaceae and Alistipes in the phylum Bacteroidetes in HIV positive individuals compared to controls.

Monaco et al. 2016 [36]

V4 region of 16S rRNA gene

40 HIV positive individuals on ART, 42 HIV positive individuals not on ART, 40 HIV seronegative individuals

• Low peripheral CD4 T cell counts associated with reduced phylogenetic diversity and species richness.

• Low peripheral CD4 T cell concentration associated with an increase in a group of bacteria such as Enterbacteriaceae, Enterococcaceae and Lactobacillaceae.