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Table 1 Main controlled studies in SIV and HIV with dietary interventions, prebiotics, postbiotics, symbiotics, and FMT

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

Population

Intervention

Study design and sample size

Outcomes

Ref

Rhesus macaques

Vancomycin

5 SIV + vancomycin

5 SIV control

Increased damage to GI tract epithelium

[60]

Rhesus macaques

Vancomycin

6 vancomycin before SIV challenge

6 control

Increased transmitter founder viruses after vancomycin

[61]

Pigtail macaques

Probiotics

5 (SIV + ART alone)

5 (SIV + ART + probiotics)

Increased GI tract CD4 + T-cell reconstitution

[63]

Pigtail macaques

Probiotics + IL-21

5 (SIV + ART alone)

5 (SIV + ART + probiotics + IL-21)

Increased GI tract CD4 + T-cell reconstitution, transient Th17 increases

[64]

Rhesus macaques

FMT

6 FMT + SIV

6 control SIV

Increased Th17 cells

[65]

Rhesus macaques

High-fat diet

8 HFD + SIV

52 historical SIV controls

Increased SIV disease progression

[66]

Pigtail macaque

High-fat diet

7 historical SIV controls

5 HFD + SIV

3 HFD

Increased SIV disease progression

[67]

Rhesus macaques

Butyrate

6 (SIV + ART alone)

7 (SIV + ART + butyrate)

Slight increase in jejunal H3 acetylation and modest microbiome alterations

[68]

PWH on ART

Fermented skimmed milk supplemented with Lactobacillus rhamnosus GG (108 cfu/mL), Bifidobacterium animalis subsp. Lactis B-12 (108 cfu/mL), and Lactobacillus acidophilus La-5 (107 cfu/mL)

Duration: 8 weeks

Randomized, double-blind, placebo controlled

trial

N = 25

Probiotics: N = 12

Placebo: N = 7

Control: N = 6

Mild D-dimer, CRP, and IL-6 reduction. No changes in microbial translocation (LPS, sCD14) or T-cell activation markers

[69]

PWH on ART

Saccharomyces boulardii (two capsules three times a day or 6 × 107 living bacteria)

Duration: 12 weeks

Randomized,d ouble-blind, placebo controlled trial

N = 35

Probiotics: N = 19

Placebo: N = 16

Decreased LBP

No changes in inflammation markers or T-cell counts

[70]

PWH diagnosed with CD4 < 350 cells/µL or AIDS starting ART

A synbiotic mixture of prebiotics, Saccharomyces boulardii, oligonutrients, essential amino acids, omega-3 fatty acids

Duration: 48 weeks

Randomized, double-blind, placebo controlled trial

N = 59

Synbiotics: N = 32

Placebo: N = 27

No effects on primary (CD4 count, CD4/CD8 ratio) or secondary (T-cell activation, bacterial translocation, inflammation, or fecal microbiota structure) endpoints

[49]

PWH on ART with CD4 < 500 cells/µL and < 50 cells/µL increase 6 months before enrolment

Lactobacillus casei Shirota

Duration: 12 weeks

Randomized, double-blind, placebo controlled trial

N = 45

• Probiotics: N = 23

• Placebo: N = 22

No effects on CD4 count, CD4/CD8 ratio, T-cell activation, or sCD14

[71] 714,353

PWH on ART on ART with CD4 > 200 cells/µL

Probiotic visbiome

For weeks 2–4, one sachet orally daily

For weeks 4–26, one sachet orally twice daily

Randomized, double-blind, placebo controlled trial

N = 73

• Probiotics: N = 42

• Placebo: N = 31

No effect on primary (sCD14) or secondary (markers of inflammation and gut permeability) enpoints

[72]

PWH on ART and CD4 < 350/ counts µL despite virologic suppression

Probiotic visbiome

Duration: 48 weeks

Randomized, double-blind, placebo controlled trial

• Probiotics: N = 18

• Placebo: N = 10

No effect on primary outcome (CD8 activation: HLA-DR + /CD38 + cells) or secondary (markers of inflammation, immune reconstitution, bacterial translocation, and gut permeability) endpoints

CD4 + T-cell activation (HLA-DR +) increased

[73]

PWH on ART and CD4 < 500 cells/µL

Probiotics: Lactiplantibacillus plantarum and Pediococcus acidilactici

Prebiotics: Pectin, inulin, oat, acacia, maltodextrin polydextrose, and partially hydrolyzed guar gum

Duration: 6 months

Randomized, double-blind, placebo controlled trial

71 patients

• Probiotics: N = 21

• Prebiotics + Probiotics: N = 32

• Placebo: N = 18

With synbiotics, slight increases of CD4 + counts and CD4/CD8 ratio, and decreased sCD14

[74]

PWH on ART and CD4/CD8 ratio < 1

Fecal microbiota transplant from three selected donors

Randomized, double-blind, placebo controlled trial

N = 29 patients

• FMT: N = 14

• Placebo: N = 15

Decreased in IFABP, increased alpha diversity, and increased Lachnospiraceae and Ruminococcaceae abundance

No effects on CD4 counts, CD4/CD8 ratio, or other markers of inflammation and bacterial translocation

[75]

MSM on ART

Supplemented Mediterranean diet (SMD) with extra-virgin olive oil and nuts

Randomized, open controlled trial

N = 60, according to SMD

• High adherence: N = 30

• Medium adherence: N = 20

• Low adherence: N = 8

Improved lipid profiles and reduced immune activation with high adherence to SMD

[76]