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Table 2 Probiotics for NAFLD treatment: human trials

From: Correlation of non-alcoholic fatty liver disease and gut microflora: clinical reports and treatment options

Reference

Study design and population

Probiotic strain used and timespan

Outcome

Study limitations

Adult

 Aller et al. 2011 [49]

DB-RCT, BP-NAFLD, (n = 30), adult

Lactobacillus bulgaricus and Streptococcus thermophilus (3 months)

The probiotic group showed substantial reductions in ALT, AST, and GGT from baseline.

Nonetheless, these studies have failed to showcase advantageous impacts on cardiovascular risk factors such as weight, blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides.

 Shavakhi et al. 2013 [50]

DB-RCT, NASH (n = 64), verified by biopsy and histological evaluation, age: 18 to 75 years

Protexin (6 month)—L. plantarum, L. delbrueckii subsp. bulgaricus, L. acidophilus, L. rhamnosus, B. bifidum, S. salvarius subsp. thermophilus, and E. faecium

TG, BMI, and TC were all considerably lowered, and levels of ALT and AST as well.

The analysis did not address the correlations between advancing age and elevated baseline ALT and AST levels.

 Wong et al. 2013 [10]

OL-RCT, HP-NASH (n = 20), age: 18 to 70 years

Lepicol (6 month)—L. plantarum, L. deslbrueckii, L. acidophilus, L. rhamnosus, and B. bifidum

Decreased AST levels and hepatic fat in NASH patients.

Small sample size and the study’s focus on Chinese participants suggests limited applicability to other populations.

 Nabavi et al. 2014 [51]

DB-RCT, NAFLD (n = 72), age: 23 to 63 years

L. acidophilus La5 and B. lactis Bb12 (8 week)

Serum glucose, triglyceride, or HDL cholesterol levels did not alter significantly. Elevated levels of LDL cholesterol, serum total cholesterol, and liver enzymes in study participants.

The lack of a control group abstaining from yogurt consumption and the utilization of ultrasonography instead of biopsy as the diagnostic criteria for NAFLD.

 Sepideh et al. 2016 [52]

DB-RCT, NAFLD (n = 42), age: 18 to 65 years

Lactocare (8 weeks)—L. casei, L. acidophilus, L. rhamnosus, L. bulgaricus, B. breve, B. longum, and S. thermophilus

Noteworthy reductions were observed in insulin resistance, IL-6, and TNF-α.

Underlying mechanisms was not discussed.

 Behrouz et al. 2017 [53]

DB-PCT, NAFLD (n = 89), age: 20–60 years

L. casei, L. rhamnosus, L. acidophilus, B. longum, and B. breve (12 weeks)

The probiotic and prebiotic groups exhibited a substantial decrease in the serum amounts of leptin, insulin, and HOMA-IR.

Quantification of fecal bacterial loads before and after the treatment was not conducted.

 Monem 2017 [54]

RCT, NAFLD (n = 30), average age: 44 years

Acidophilus capsule—Lactobacillus acidophilus (1 month)

Considerable fall in ALT and AST levels in the liver

Underlying mechanisms was not discussed.

 Ahn et al. 2019 [55]

DB-PCT, NAFLD (n = 68), age: 19 to 75 years

L. rhamnosus, L. acidophilus, L. paracasei, P. pentosaceus, B. lactis, and B. breve (12 weeks)

Substantial drop in body weight and intrahepatic fat.

A larger sample size and more compelling evidence, such as MR elastography or liver biopsy results, along with long-term follow-up data, are required.

 Duseja et al. 2019 [56]

DB-RCT, BP-NAFLD (n = 39), age: >18 years

L. paracasei DSM 24733, L. plantarum DSM 24730, L. acidophilus DSM 24735, and L. delbrueckii subsp. Bulgaris DSM 24734, B. longum DSM 24736, B. infantis DSM 24737, B. breve DSM 24732, and S. thermophilus DSM 24731 (12 months)

Significant improvements were made in NAS score, ALT, cytokine profile, and hepatocyte ballooning.

Small sample size.

 Chong et al. 2021 [57]

Randomized DB-PCT, NAFLD (n = 35), age: 25–70 years

VSL#3 (10 weeks)—Lactobacillus, Bifidobacterium, and Streptococcus

Improvements in metabolic markers, including insulin sensitivity, and a decrease in inflammation, were seen.

The study is limited by its small sample size and the short duration of VSL#3 treatment.

 Mohamad Nor et al. 2021 [58]

Randomized DB-PCT, NAFLD (n = 39), age: >18 years

L. acidophilus BCMC 12130, L. casei subsp. BCMC 12313, L. lactis BCMC 12451, B. bifidum BCMC 02290, B. infantis BCMC 02129, and B. longum BCMC 02120 (6 month)

Probiotics appeared to have the capacity to regulate mucosal immune response and shield NAFLD patients from increased intestinal permeability.

Small sample size and stool sample was not collected for analysis.

 Ayob et al. 2023 [59]

Randomized DB-PCT, NAFLD (n = 72), age: >18 years

L. acidophilus BCMC 12130, L. casei subsp. BCMC 12313, L. lactis BCMC 12451, B. bifidum BCMC 02290, B. infantis BCMC 02129, and B. longum BCMC 02120 (6 months)

Probiotics’ ability to reverse dysbiosis resulted in decreased release of inflammatory cytokines, which suggested that less bacterial toxin was being transported across the GLA.

Limited sample size, and the trial was carried out at a single health center.

Children

 Vajro et al. 2011 [60]

DB-RCT, NAFLD, (n = 20)

Lactobacillus GG (8 week)

Probiotics considerably raised ALT levels and peptidoglycan polysaccharide content.

The studies do not provide insights into the mechanism(s) responsible for the enhancement of ALT values in patients.

 Alisi et al. 2014 [61]

DB-RCT, BP-NAFLD (n = 44), overweight children

VSL#3 (4 months)—Lactobacillus, Bifidobacterium, and Streptococcus

Triglycerides, HOMA, and ALT did not change, whereas decrease in BMI and elevated levels of GLP-1 and aGLP1.

Further metabolomic analysis required.

 Miccheli et al. 2015 [62]

DB-RCT, NAFLD (n = 31)

VSL#3 (4 months)—Lactobacillus, Bifidobacterium, and Streptococcus

There were substantial improvements in BMI, total and active GLP-1 levels, AST, and the prevalence of fatty liver, but not in TGs, cholesterol, HDL, or glycometabolism.

Additional research is necessary to comprehend the impact of gut microbiota on metabolite profiles.

 Rodrigo et al. 2022 [63]

Randomized DB-PCT (n = 84), age: 5 to 15 years

Bio-Kult 14 strain probiotic capsule (6 months)—B. subtilis PXN 21, B. bifidum PXN 23, B. breve PXN 25, B. infantis PXN 27, B. longum PXN 30, L. acidophilus PXN 35, L. delbrueckii ssp., bulgaricus PXN 39, L. casei PXN 37, L. plantarum PXN 47, L. rhamnosus PXN 54, L. helveticus PXN 45, L. salivarius PXN 57, L. lactis ssp. lactis PXN 63, and S. thermophilus PXN 66

Significant decreases in triglycerides, ALT, AST, alkaline phosphatase, body mass index, and AST/ALT ratio were also seen.

It is necessary to investigate the effect on glucose metabolism in obese children such as insulin sensitivity, glycemic control, and the development of diabetes mellitus.