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. 2022 May 18;14(10):2111. doi: 10.3390/nu14102111

Table 3.

In vivo studies of herb–gut microbiome interactions of medicinal plants used for mental health performed in experimental animals or human volunteers.

Investigated Plant, Plant Part Extract, Sample Preparation Animal or Study Groups (n = Number of Analyzed Individuals) Animal
Species, Volunteers		 Conditions Method for Microbiome Analysis Microbiome Changes Method for Metabolite Detection Metabolites Reference
Aloysia citrodora, folium ethanolic extract (25%) (LCE) 6 groups:
control diet (CD); CD + LCE (25 mg/kg); control high-fat diet (HFD); HFD + LCE (1 mg/kg); HFD + LCE (10 mg/kg); HFD + LCE (25 mg/kg) (n = 10 mice per group)		 male C57BL/6J mice (7–9 weeks old) treated for 6 weeks; colonic luminal contents collected V4–V5 region of 16S rRNA gene, NGS (Illumina) LCE reduced the enhanced Firmicutes/Bacteroidetes ratio and relative abundance of Bacilli in HFD mice; reversed reduced Bacteroidia, Erysipelotrichia, Cytophaga, and Akkermansia relative abundances in HFD mice - - [62]
Amygdalus communis, semen almonds 2 groups:
low-fat diet (LFD) (n = 23); almond-based low-carbohydrate diet (a-LCD); 56 g almonds/day (n = 22)		 patients with type 2 diabetes mellitus (71.98 ± 5.63 years) treated for 3 months; fecal samples collected V4–V5 region of 16S rRNA, gene sequencing (Illumina) a-LCD: rel. decrease in Bacteroidetes and Bacteroides; rel. decrease in Ruminococcus, Eubacterium, and Roseburia - - [68]
whole, dry-roasted almonds 2 groups:
almond group (57 g/day) (n = 38); cracker group (77.5 g/day of graham crackers) (n = 35)		 female and male young adults (BMI 18–41 kg/m2; 18–19 years) treated for 8 weeks; fecal samples collected at baseline and after 8 weeks V4–V5 region of 16S rRNA, gene sequencing (Illumina) increase in alpha diversity in the almond group compared to the cracker group
rel. decrease in Bacteroides fragilis 		- - [67]
almonds three groups:
almonds, 0 g/day; 42 g/day; 84 g/day; n = 18		 healthy adults (10 male, 8 female) 3 feeding periods of 18 days separated by a 2-week washout period; fecal sample collection on first and last days of each feeding period 16S rRNA gene, NGS (454 pyrosequencing), targeting universal primers 27F and 533R; qPCR with specific primers for Bifidobacteria, lactic acid bacteria, and Eubacteria decrease in lactic acid bacteria by almond consumption; no change in Bifidobacteria by almond consumption - - [69]
natural almonds; roasted almonds; almond butter 5 periods:
0 g/day of almonds (control diet) (n = 18); 42 g/day of whole, natural almonds (n = 17); 42 g/day of whole, roasted almonds (n = 18); 42 g/day of roasted, chopped almonds (n = 15); 42 g/day of almond butter (n = 18)		 female and male volunteers (BMI 29.7 + 4.4 kg/m2; 56.7 + 10.2 years) 5 diet periods of 3 weeks, separated by 1-week non-controlled diet breaks; fecal sample collection at the end of each diet treatment period V4 region of 16S rRNA gene, NGS (Illumina) rel. decrease in Actinobacteria, Bifidobacterium, and Parabacteroides by almond consumption;
rel. increase in Lachnospira, Roseburia, and Oscillospira by chopped almond diet; rel. increase in Lachnospira by whole, roasted almond diet; increase in Dialister by whole, natural almond diet		 - - [64]
Astragalus membranaceus, radix fine powder (70% astragalan, 10% total saponins) two groups: control (0.5% CMC-Na buffer), astragalus (1 g/kg bwd) (n = 5 per group) BKS.Cg-Dock7m +/+ Leprdb/Nju mice (5 weeks old) treated for 15 days, fresh feces collected V3–V4 region of 16S rRNA gene, NGS (Illumina) microbial function prediction (PICRUst, KEGG, STAMP) composition analysis:
rel. increased (significant): Oscillibacter; LEfSe: inhibited growth: Clostridium cluster XI; increased growth: Lactobacillus and Bifidobacterium 		- - [71]
Camellia sinensis, folium water extracts of
green tea (GTWE); black tea (BTWE); oolong tea (OTWE)		 5 groups:
LFD, 9.4% of calories from fat; HFD, 40% of calories from fat; HFD + 1% GTWE; HFD + 1% BTWE; HFD + 1% OTWE (n = 12 per group)		 male C57BL/6J mice (7 weeks old) treated for 28 weeks; fecal samples were collected at week 28 V3–V4 region of 16S rRNA gene, NGS (Illumina) increase in microbial richness in all tea groups; rel. decrease in Rikenellaceae, Desulfovibrionaceae, Alistipes, and Rikenella in GTWE group; rel. increase in Lachnospiraceae_NK4A136_group, Acetatifactor, and Ruminiclostridium_9 in GTWE group SCFA analysis by GC increase in total SCFAs, propionic acid, and valeric acid [74]
purple-leaf tea leaf powder (PLT) 4 groups:
normal diet (ND); HFD; HFD-1% PLT; HFD-3% PLT (n = 8 per group)		 male C57BL/6J mice (5 weeks old) treated for 10 weeks, fecal samples were collected V3–V4 region of 16S rRNA gene, NGS (Illumina) HFD-PLT groups compared to HFD group:
rel. increase in microbial richness; decrease in Firmicutes/Bacteroidetes ratio; rel. increase in Ruminococcaceae		 - - [75]
water extracts from:
green tea (GTE); black tea (BTE); yellow tea (YTE); oolong tea (OTE); white tea (WTE); dark tea (DTE); hawk tea (HTE)		 9 groups:
healthy group; DSS group; GTE + DSS group; WTE + DSS group; YTE + DSS group; OTE + DSS group; BTE + DSS group; DTE + DSS group; HTE + DSS group; (n = 6 per group)		 Kunming female mice (7–8 weeks old) treated for 14 days; fecal samples were collected V3–V4 region of 16S rRNA gene, NGS (Illumina) in GTE group:
increase in microbial diversity; rel. decrease in Bacteroides, Oscillibacter, Mucispirillum, Helicobacter, and Brachyspira; rel. increase in Bifidobacterium and Ruminococcaceae_UCG-014		 SCFA analysis by HPLC increase in acetic acid, propionic acid, and butyric acid [76]
green tea water extract (GTE); dark tea water extract (DTE) 3 groups of healthy mice:
normal group; GTE (5 mg/kg) group; DTE (5 mg/kg) group		 female C57BL/6 mice (7–8 weeks old) treated for 4 weeks; fecal samples were collected after 4 weeks V3–V4 region of 16S rRNA gene, NGS (Illumina) bacterial community richness and diversity unchanged in healthy mice; healthy GTE group:
rel. increase in Lactococcus, Akkermansia, Lactobacillus intestinalis, Alistipes, and Parabacteroides distasonis; rel. decrease in Turicibacter, Romboutsia, Allobaculum, Ileibacterium, and Muribaculum 		- - [77]
Cannabis sativa, herba inflorescence extracts (99.9% ethanol): cannabidiol (CBD)-rich CN1 extract; tetrahydrocannabinol (THC)-rich CN2 extract; CN6 extract (CBD/THC ca. 1:1) 5 groups:
ND; high-fat + 1% cholesterol + 0.5% cholate diet (HFCD); HFCD diet + CN1 (HFCD+CN1); HFCD diet + CN2 (HFCD+CN2); HFCD diet + CN6 (HFCD+CN6) (n = 8 per group)		 male C57BL/6J mice (7–8 weeks old) treated for 6 weeks, 5 mg/kg BW of extract administered every 3 days; cecal contents were collected after sacrifice V3–V4 region of 16S rRNA gene, NGS (Illumina) rel. decrease in Bacteroidetes and decrease in Bacteroidetes/Firmicutes ratio in HFCD+CN1 group compared to HFCD group; no significant microbiota changes in HFCD+CN2 and HFCD + CN56 - - [79]
Centella asiatica, herba ethanolic extract (75%) 6 groups:
control, model group (DSS-induced colitis), DSS+5-aminosalicyclic acid, DSS+C. asiatica (100, 200, and 400 mg/kg) (n = 8 per group)		 male Balb/c mice (22–24 g, 8 weeks old) treated for 7 days, cecum contents collected after sacrifice V4 region of 16S rRNA gene NGS (Illumina) DSS+C. asiatica (400 mg/kg):
rel. increase: Firmicutes; rel. decrease: Proteobacteria, Helicobacter, Jeotgalicoccus, and Staphylococcus 		- - [82]
Citrus aurantium ssp. aurantium, flos ethanolic extract (85%) partitioned to ethyl acetate subextract (EA) 6 groups:
control ND; model control HFD; HFD+ low, middle, and high citrus ethyl acetate (LEA (50 mg/kg), MEA (100 mg/kg), HEA (200 mg/kg)); HFD+simvastatin
(n = 8 mice per group)		 male C57BL/6 mice (weighing 16–17 g, 4 weeks old) treated for 12 weeks; fresh fecal pellets collected V3–V4 region of 16S rRNA gene, NGS (Illumina) HEA increased microbiota diversity and richness; decreased Firmicutes/Bacteroidetes ratio;
rel. decrease Erysipelotrichaceae and others
rel. increase: Bifidobacteria and others		 - - [87]
Crocus sativus, stigma saffron (not defined) two groups:
control (water), saffron in drinking water (120 mg/day) (n = 10 per group)		 rats (not defined) treated for 4 weeks; stool samples collected before and after 4 weeks 16S rRNA gene NGS (Illumina) using universal bacterial primers strong rel. reduction: Cyanobacteria, Proteobacteria
less strong rel. decrease: Bacteroidetes, Firmicutes
rel. increase: Spirochaetes, Tenericutes, Candidatus saccharri 		- - [94]
Curcuma longa, rhizoma turmeric powder (2.5% curcumin); alcoholic turmeric extract containing curcumin and turmeric oil fraction three groups:
control diet (CD); CD + 100 mg turmeric powder; CD + 20 mg turmeric extract
(n = 10 rats per group)		 male Wistar albino rats (21 days old; ≈32 g) five animals of each group killed after 3 months, others after 2 years; cecal contents collected after sacrifice agar dilution (0.1% peptone for aerobes; sterile mineral solution for anaerobes) significant decrease after 3-month treatment:
total aerobes, Lactobacilli
significant increase after 3-month treatment:
total anaerobes, Clostridium perfringens, and coliforms
significant decrease after 2-year treatment: coliforms		 - - [97]
Dioscorea oppositifolia, rhizoma dried Chinese yam powder (CY) five groups:
normal control (NC) group (water); model control (MC) group (antibiotic-associated diarrhea, AAD); low-dosage (CL) group (AAD + 4.28 g/kg BW CY suspension); medium-dosage (CM) group (AAD + 8.56 g/kg BW CY suspension); high-dosage (CH) group (25.68 g/kg BW CY suspension) (n = 10 per group)		 male Balb/c mice (7 weeks old) days 1–5: MC, CL, CM, and CH groups: ampicillin (22.4 g/kg BW, two times per day); days 6–15: water for MC group, CY for CL, CM, and CH groups; fecal samples were collected bacterial counting, specific agar plates for Bifido-bacteria, lactobacilli, Enterococcus, and Clostridium perfringens;
denatured gradient gel electrophoresis (DGGE) and V3 region 16S rRNA gene sequen-cing of DGGE target bands		 increase in Bifidobacteria and Lactobacilli in CH group; decrease in Enterococcus in CH group and Clostridium perfringens in CL, CM, and CH groups;
increase in Bacteroides spp. and Clostridium spp. in CL, CM, and CH groups		 SCFA analysis by GC-FID increase in total SCFAs in CL, CM, and CH groups [99]
Chinese yam extract (hot water) (CY) three groups:
NC; antibiotic group (A; 50 mg/kg BW imipenem/cilastatin Na); CY group (ADR; 50 mg/kg BW imipenem/cilastatin Na + 3.4 g/kg BW CY) (n = 6 per group)		 SPF-grade male Wistar rats (100 ± 10 g) treated for 21 days; fecal samples were collected V3–V4 region of 16S rRNA gene, NGS (Illumina) ADR group:
increase in microbial diversity reduced by antibiotic; rel. increase in Lachnospiraceae, Ruminococcaceae, Clostridiales, and Firmicutes; rel. decrease in Blautia, Prevotella, and Eisenbergiella 		metabolic profile analysis by UPLC-Q-TOF/MS CY administration returned fecal sample metabolite profile to normal [100]
Eleutherococcus senticosus, plant part not specified ethanolic extract (EE) four groups:
control, EE (30 g/100 kg), Enterococcus faecium AL41 (EFAL41), EFAL41 + EE (n = 24 rabbits in each group)		 post-weaned rabbits (Hyplus breed) (5 weeks old) treated for 42 days; fecal sampling on day 0/1 (start of experiment), day 21, and day 42; on days 21 and 42, 3 animals per group were sacrificed agar dilution methods on specified agars for enterococci, EFAL41, coagulase-negative and coagulase-positive staphylococci, Clostridium difficile, coliforms, pseudomonads EE group:
reduction in: coagulase-negative staphylococci and Clostridia on day 21		 cecal lactic acid and SCFA analysis using GC (days 21 and 42, 3 animals per group were sacrificed) different concentrations of propionic acid in all experimental groups in comparison to control on day 42 [104]
Ginkgo biloba, folium polysaccharide-rich water extract (GPS) stage 1–4 groups: control; unpredictable chronic mild stress mice (UCMS); UCMS + GPS (300 mg/kg BW); UCMS + paroxetine (30 mg/kg BW), (n = 10 per group); stage 2 fecal microbiota transplant (2 groups): mixed antibiotics, oral gavage of fecal samples from donor mice (UCMS-FMT or GPS-FMT) (n = 8 per group)
Lactobacillusreuteri treatment (3 groups): control; UCMS; UCMS + oral gavage of L. reuteri (n = 8 per group)		 male SPF BALB/c mice (3–4 weeks old) treated for 4 weeks, fresh feces collected; behavioral experiment after 30 days of GPS/paroxetin treatment, FMT, or L. reuteri treatment V3–V4 region of 16S rRNA gene, NGS (pyrosequencing) antidepressant effect in forced swimming test in UCMS-GPS group vs. UCMS group, and in GPS-FMT group vs. UCMS-FMT group;
GPS reversed gut dysbiosis induced by UCMS; 113 differential OTUs between UCMS-GPMS and UCMS groups		 - - [106]
Glycine max, fructus legume powder; isoflavone content in Glycine soja (HFG) 788.77 µg/g, in Glycine max (HFB) 139.72 µg/g four groups:
control (normal chow; NCD); standard HFD; HFD with 20% HFG; HFD with 20% HFB
(n = 12 mice per group)		 male C57BL/6J mice (7 weeks old, 18–20 g) treated for 11 weeks; fresh feces collected in the last week in the morning V3–V4 region of 16S rRNA gene, NGS (Illumina) reversal of HFD-induced gut microbiota changes in HFB and HFG
rel. increase: Bacteroidetes, Proteobacteria, Allobaculum, Parasutterella, Anaerotruncus, Helicobacter, Alistipes;
rel. decrease: Verrucomicrobia, Akkermansia 		analysis of fecal SCFA content by HPLC/PDA detector total SCFA and acid concentrations reduced in HFD group, but elevated in HFG- and HFB- supplemented groups; acetic and propionic acids and total SCFAs higher in HFG than in HFB [112]
soybean husk with 0.9 mg/g total flavonoids two groups:
cellulose powder (10 g) or soybean husk powder (5.6% of total diet) (n = 4 per group)		 healthy Shiba dogs (7–48 months in age and 7.5 ± 1.7 kg in body weight) treated for 7 days; feces collected on morning and evening of days 6 and 7 qPCR assay using specific primers increase: total lactobacilli, Clostridium cluster IV, Faecalibacterium prausnitzii, Clostridium cluster XIVa, Bacteroides-Prevotella-Porphyromonas group;
decrease: Clostridium cluster XI		 analysis of SCFA by GC-MS; D/L-lactic acid assay increase: total SCFAs, acetic, butyric, and lactic acids (p < 0.05)
decrease: indole and skatole		 [110]
soy (590 mg/isoflavones kg diet (genistein and daidzein equivalents)) 4 groups:
OVX + soy; SHM + soy; OVX + soy-free (control); SHM + soy-free (control) (n = 10 rats per group)		 female rats bred for low-running capacity, either ovariectomized (OVX) or sham-operated (SHM) (27 weeks old) treated for 28 weeks; cecal digesta samples collected V3–V4 region of 16S rRNA gene, NGS (Illumina) OVX + soy and SHM + soy:
rel. increase: Bacteroidetes, Prevotella, Lachnospiraceae, Dorea, Phascolarctobacterium, rc4-4, Sutterella
rel. decrease: Firmicutes, Coprococcus, SMB53, Clostridiaceae, Desulfovibrionaceae, Adlercreutzia, Bifidobacterium CF231, Desulfovibrio, Roseburia, Treponema, Peptostreptococcaceae;
lower Firmicutes/Bacteroidetes ratio (p < 0.001)		 - - [113]
Gynostemma pentaphyllum, folium Gynostemma pentaphyllum saponins (GpS) 3 FMT donor groups:
GpS treatment (Apc+GpS 300 mg/kg BW); non-treatment (Apc-GpS); wild-type (WT) control (C57BL/6J mice—GpS, B6 group)
4 FMT groups:
control group (no FMT), B6 FMT, Apc-GpS FMT, and Apc+GpS FMT
(n = 8 per group)		 male C57BL/6J (WT) and ApcMin/+ (colon cancer model) mice (4–6 weeks) treated for 8 weeks; at the end of week 4, fresh feces collected every 3 days from FMT donors;
FMT groups received transplants every 3rd day for 4 consecutive weeks		 enterobacterial repetitive intergenic consensus (ERIC)-PCR and qPCR with taxon-specific 16S rRNA gene primers Apc/GpS FMT group:
significant increase in Bacteroides, Bacteroidetes/Firmicutes ratio, beneficial bacteria such as Bacteroides, Bifidobacterium, Lactobacillus, Clostridium Cluster IV, and Faecalibacterium prausnitzii 		[119]
Gynostemma pentaphyllum saponins (GpS); 50 mg/mL in 0.5% carboxymethyl cellulose four groups:
nonxenograft-control, nonxenograft-GpS (n = 6 per group); xenograft-control and xenograft-GpS; (750 mg/kg BW; n = 7 per group)		 athymic nude mice (BALB/c-nu/nu); xenograft performed by injecting 106 R6/GFP-ras-transformed cells into the flank (7 to 8 weeks old) treated for 12 days; animal feces collected from each mouse for two consecutive hours on day 0 (before xenograft), and day 5 and day 10 after GpS treatment ERIC-PCR; 3 fecal samples randomly picked from each experimental group on day 10 for further 16S rRNA gene NGS (454 pyrosequencing) GpS induced alteration in microbiota in xenograft, but not in nonxenograft mice; Clostridium cocleatum and Bacteroides acidifaciens rel. increase by GpS treatment in xenograft and nonxenograft mice - - [117]
Gynostemma pentaphyllum saponins (GpS); 50 mg/mL in 0.5% carboxymethyl cellulose three groups:
WT-control, WT-GpS, ApcMin/+-control, ApcMin/+-GpS; 500 mg/kg (n = 12 mice per group)		 heterozygous male ApcMin/+ (C57BL/6J-ApcMin/+) and female WT C57BL/6J mice (6 weeks of age) treated for 8 weeks; fecal samples collected from for two consecutive hours before treatment and weekly after treatment ERIC-PCR; 5 fecal samples randomly picked from each experimental group on week 8 for further 16S rRNA gene NGS (454 pyrosequencing) GpS rel. increase: Bacteroides acidifaciens, Bifidobacterium pseudolongum, Clostridium cocleatum, Lactobacillus intestinalis, Parabacteroides distasonis, Streptococcus thermophilus, and Bacteroidetes/Firmicutes ratio
GpS rel. decrease: Acinetobacter lwoffii and sulfate-reducing bacteria		 - - [116]
Gynostemma pentaphyllum saponins, saponin content 85% (GpS) 2 groups: control group (water), GpS group (500 mg GS/kg BW 1× per day) (n = 10 per group) male C57BL/6 mice (8 weeks old) treated for 15 days; feces collected for 2 consecutive hours on days 0, 5, 10, and 15 upon treatment ERIC-PCR; qPCR with primers targeting 16S rRNA gene of specific bacterial groups GpS group vs. control: increased: Bacteroidetes, Bacteroidetes/Firmicutes ratio, Bacteroides spp., Lactobacillus spp., Faecalibacterium prausnitzii
decreased: Firmicutes		 - - [120]
Gynostemma pentaphyllum (GP) decocted twice with 4 L water (2 g/mL) 6 groups:
control, model group (HFD-induced nonalcoholic fatty liver disease, NAFLD), NAFLD + positive control (22.8 mg/kg DLPC), NAFLD + GP, 6 g/kg BW (GPH), NAFLD+ GP, 3 g/kg BW (GPM); NAFLD + GP, 1.5 g/kg BW (GPL) (n = 10 per group)		 male adult Sprague Dawley rats (180–220 g) rats fed with chow diet or HFD for 8 weeks; from week 5, treated for 4 weeks; cecum, contents collected after sacrifice V3–V4 region of 16S rRNA gene;
V4 and V9 regions of 18S rRNA gene, NGS (Illumina); PCR of ITS1 and ITS2 regions		 GP treatment shifted microbiota composition towards that of healthy control; GP decreased Firmicutes/Bacteroidetes ratio to a value comparable to healthy control; GP rel. increase: Lactococcus; GP rel. decrease: pathogenic bacteria, including Ruminococcus spp. - - [118]
100 g G. pentaphyllum dry herb boiled in water (1.25 g/mL) (GP) 3 groups:
control (chow diet + water), model group (HFD-induced NAFLD + water), GP treatment group (HFD-induced NAFLD + GP; 11.7 g/kg BW (12 mL GP/kg BW)		 male C57BL/6J mice (6 weeks old) feeding with chow diet or HFD for 28 weeks; treatment from week 13 on; 6 animals per group picked for feces collection (once per day on 3 consecutive days) V3–V4 region of 16S rRNA gene, NGS (Illumina) GP restored reduced gut microbial diversity and microbial shifts induced by HFD: rel. decrease in the enhanced Firmicutes levels including genera Eubacterium, Blautia, Clostridium, and Lactobacillus; rel. increase in the reduced Parasutterella levels - - [115]
Humulus lupulus, strobile hop extract suspended in sesame oil; hop extract (HE) (5.1 mg/g 8-prenylnaringenin, 6.3 mg/g xanthohumol), 400 mg/kg BW 5 groups:
OVX placebo (sesame seed oil, n = 11), OVX plus HE (n = 11), OVX plus 17β-estradiol (n = 9), SHAM placebo (sesame seed oil, n = 10), SHAM plus HE (n = 8)		 female C57BL/6 retired breeder mice (7 months old); ovariectomized (OVX) or sham-operated (SHAM) duration: 12 weeks
surgery after week 2; treatment started 4–7 days post-surgery;
fecal samples from week 10 (SCFAs), cecal contents (microbiota analysis)		 V3–V4 region of 16S rRNA gene, NGS (Illumina) no influence on total bacterial abundances;
rel. decrease Akkermansia muciniphila in SHAM plus HE group compared to SHAM placebo and OVX plus 17β-estradiol group; no reduction in OVX plus HE group		 SCFA analyses using GC-FID no significant differences in fecal SCFA levels among groups [124]
Hypericum perforatum L., herba H. perforatum extract (8.94% total flavonoids, 0.026%
hyperoside, 0.323% hypericin) (HP)		 3 groups:
OVX group; OVX-HP group (extract 300 mg/kg BW HP); sham group (n = 8 per group)		 female Sprague Dawley rats (260–300 g, 6–8 weeks old) treated for 12 weeks; feces were collected for 3 days before the end of the experiment V3–V4 region of 16S rRNA gene, NGS (Illumina) HP group:
increased Firmicutes/Bacteroidetes ratio; rel. increase Firmicutes and Verrucomicrobia; rel. decrease Bacteroidetes, Elusimicrobia, and Gemmatimonadetes		 SCFA analysis by GC-FID HP group:
increased acetic acid, propionic acid, butyric acid, valeric acid, and hexanoic acid		 [126]
Lycium barbarum L., fructus goji berry powder 2 groups:
standard rodent diet (Con); Con diet + 1% goji (n = 7 per group)		 male IL-10-deficient mice (6 weeks old) treated for 10 weeks; fecal samples (colonic contents) were collected at necropsy V4 region of 16S rRNA gene, NGS (Illumina) goji group:
increase in Firmicutes/Bacteroidetes ratio; rel. increase in Actinobacteria, Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae, Bifidobacterium, Clostridium XVIII, Roseburia sp., Clostridium leptum, and Faecalibacterium prausnitzii;
rel. decrease in Peptostreptococcaceae		 SCFA analysis by GC-FID increase in butyric acid and isovaleric acid [135]
Melissa officinalis, folium lemon balm water extract (LB) (2.76 mg rosmarinic acid/100 mg dried raw material) 2 groups:
control (water); LB group (LB dissolved in water, 500 mg LB/day/mouse) (n = 5 per group)		 C57Bl/6J male ob/ob mice (12 weeks old) treated for two weeks; gut (fecal) microbiome analyzed before and after treatment V3–V4 region of 16S rRNA gene, NGS (Illumina) LB group:
increase: Chao-1 diversity index and Porphyromonadaceae		 metabolomic analysis of cecum content for SCFAs and other metabolites significantly higher levels of butyrate, propionate, and ethanol; significantly lower level of lactate [140]
Morus alba L., folium dried and powdered mulberry leaves three groups:
control group, LFD, 10% calories from fat; HFD, 60% calories from fat; mulberry group (M + HFD; HFD plus 20% M) (n = 6 per group)		 male C57BL/6J mice (15–20 g, 4 weeks old) 8 weeks until weight difference between HFD and LFD is ca. 20%; treated for 13 weeks; feces collected after adaptation, HFD-induced obese model construction, and at the end V3–V4 region of 16S rRNA gene, NGS (Illumina) increase in Bacteroidetes/Firmicutes ratio; rel. decrease in Firmicutes and Proteobacteria; rel. increase in Bacteroidetes and Akkermansia - - [137]
Panax ginseng,
radix		 red and white Korean ginseng powder (WG, RG) three groups:
control (basal diet), WG group (7.0% w/w of diet WG), RG group (7.0% w/w of diet RG)
(n = 10 per group)		 Sprague Dawley male rats treated for 21 days, postmortem: ileum contents (anterior to the ileocecal valve) collected qPCR with primers for all bacteria, Lactobacillus, Bifidobacterium, Escherichia coli, Clostridium cluster I, Bacteroides-Prevotella-Porphyromonas group RG and WG groups: significantly higher number of total bacteria (p = 0.014) and Lactobacillus strains (p = 0.018) - - [144]
freeze-dried granulated Panax ginseng extracts g Panax ginseng extract (4 g two times/day), no placebo group (n = 10 women) women aged 40–60 years and body mass index ≥ 25 kg/m2 8-week clinical trial, fresh human stools collected on the 1st visit day (week 0) and the last day (week 8) V1–V3 region of 16S rRNA gene, NGS (454 pyrosequencing) rel. abundance of Anaerostipes decreased after ginseng intake; subgroup analyses with effective (EWG) and ineffective weight loss groups (IWG): increased in EWG: rel. abundance of Anaerostipes and Eubacterium_g5; increased in IWG: Lactobacillus; rel. abundance of Bifidobacterium, Escherichia, and Clostridium_g23 in EWG significantly lower than in IWG [143]
ethanolic extract (80%) (PGE) PGE (100 mg total saponins/kg BW) (n = 60 rats), no control group male Sprague Dawley rats (7 weeks old, weight: 220 ± 20 g) treated for 12 h; colonic content samples collected V1–V3 region of 16S rRNA gene, NGS (Illumina) subgroup with low-efficiency metabolism (LEM) and high-efficiency metabolism (HEM): rel. abundance of Alcaligenaceae, Coriobacteriaceae, Bifidobacteriaceae, S24-7, Erysipelotrichaceae, Peptostreptococcaceae, and Campylobacteraceae significantly higher in HEM; Lachnospiraceae, Prevotellaceae, Porphyromonadaceae, Defluviitaleaceae, Lactobacillaceae, and Veillonellaceae significantly lower in HEM LC-MS/MS (MRM mode, precursor-product ion pairs) protopanaxadiol-type ginsenosides: selective elimination of the C-20 and C3- terminal sugar moieties to compound K, or of the C-20 sugar chain to ginsenoside Rg3; protopanaxatriol-type ginsenosides: C-20 and C-6 sugar moieties hydrolyzed to protopanaxatriol [145]
ginseng extract (not defined) 2 groups:
control (distilled water), ginseng extract (100 mg/kg; n = 9 per group)		 male Wistar rats (34 weeks with 300 g) treated for 34 weeks, intestinal (cecum, ileum) contents collected after sacrifice V3 region of 16S rRNA gene, NGS (pyrosequencing with the GS FLX platform) rel. increase in ginseng group: Bifidobacterium, Lactobacillus, Methylobacteriaceae, and Parasutterella untargeted GC-TOFMS ginseng group: 25 significantly changed metabolites from cecum and 35 from ileum;
upregulated:
amino acids, arachidonic acid, polyamines, and organic acids;
downregulated: linoelaidic acid, palmtelaidic acid, oleic acid, and glycerol		 [142]
ginseng saponin extract (80% saponins) (GS); red ginseng saponin extract (80% saponins (RGS)) 3 groups:
control group (water); GS group (500 mg GS/kg BW 1× per day); RGS group (500 mg RGS/kg BW 1× per day)
(n = 10 per group)		 male C57BL/6 mice (8 weeks old) treated for 15 days; feces collected for 2 consecutive hours on days 0, 5, 10, and 15 upon treatment ERIC-PCR; qPCR with primers targeting 16S rRNA gene of specific bacterial groups GS group vs. control: increased: Lactobacillus
RGS group vs. control:
increased: Bifidobacterium, Clostridium Cluster IV		 [120]
Panax quinquefolius, radix ethanolic extract (70%) PQE 2 groups:
drinking water; metronidazole-supplemented drinking water; after 7 days, mice received PQE (30 mg/kg/day) (n = 3 per group)		 male C57BL6 mice (6–8 weeks) treated for 3 days, fecal samples collected - - HPLC/TOF-MS compound K detected in feces from mice treated with no antibiotic; undetectable in feces of metronidazole- pretreated mice [148]
air-dried American ginseng powder 1 group:
2 g American ginseng powder per day for 7 days (n = 6); no control		 healthy male volunteers (ages 18–45 years) day 1 (control) and day 7: feces samples collected - - LC-Q-TOF-MS 16 metabolites in feces: compound K major metabolite; Rk1 and Rg5, Rk3 and Rh4, Rg6 and F4 produced via dehydration [150]
air-dried American ginseng powder 1 group:
2 g American ginseng powder in capsules per day for 7 days (n = 6), no control		 healthy male volunteers (ages 18–45 years); three on Asian diet and three on Western diet day 1 (control) and day 7: feces samples collected - - LC-Q-TOF-MS higher relative abundance in Asian diet subjects: ginsenoside Rb1;
higher relative abundance in Western diet subjects:
compound K, ginsenoside Rh2		 [151]
ethanolic extract (70%) AGE 4 groups:
control, azoxymethane/DSS-induced colitis model group, AGE low dose (15 mg/kg/day), AGE high dose (30 mg/kg/day)
(n = 10 per group)		 male A/J mice (6 weeks old with 18–22 g) treated from day 1 to week 13; fecal samples collected during weeks 1, 2, 5, 8, and 13 terminal-restriction fragment length polymorphism (T-RFLP) with broad-range primers for bacterial domain, followed by
16S rRNA gene NGS Illumina)		 AGE vs. model group: increased rel. levels of Firmicutes, decreased rel. levels of Bacteroidetes and Verrucomicrobia untargeted GC/TOF-MS major metabolites: compound K, ginsenoside Rg3, and protopanaxadiol [152]
Paullinia cupana, semen guarana seed powder 3 groups:
guarana (0.021 g/kg); caffeine (0.0007 g/kg); saline (1.0 mL/kg) (n = 10 per group)		 male Wistar rats (250–300 g) treated for 21 days; fecal samples were collected 16S rRNA gene, NGS (Ion PGM System) rel. decrease in Bacteroidetes and Prevotella, rel. increase in cyanobacteria in guarana group compared to caffeine and saline group; decrease in Lactobacillus in caffeine and guarana group - - [156]
guarana seed powder (Gua) 4 groups:
control diet (low-fat, CD); CD + 0.5% Gua; Western diet (WD; high fat); WD + 0.5% Gua (n = 12 per group)		 male Wistar rats (8 weeks old) treated for 18 weeks; fecal samples were collected during week 16 V1–V3 region of 16S rRNA gene, NGS (Illumina) WD + 0.5% Gua compared to WD:
increase in Butyricicoccus and Streptococcus, decrease in Holdemania 		- - [157]
Polygala tenuifolia, radix ethanolic extract (75%) RPE 3 groups:
control (saline), 0.5 h group, and 1.5 h group (both RPE 2 g/kg)
(n = 6 per group)		 male Sprague Dawley rats (200 ± 20 g) treated for 6 days - - targeted UHPLC-Q-TOF-MS feces of RPE groups: 44 native RPE constituents (3 xanthones, 1 sucrose ester, 9 oligoesters, 33 saponins), and 29 metabolites [160]
water extract (100 g radix polygalae powder refluxed at 100 °C with 1 L water) PGW 3 groups:
normal diet (ND; n = 8),
HFD control (HFD-C), HFD- polygala group (HFD-PGW) (PGW dissolved in distilled water orally once daily, dose not given) (n = 10 per group)		 male ICR mice (4 weeks old) treated for 5 weeks after model construction, fecal samples collected after 5 weeks treatment V3–V4 region of 16S rRNA gene, NGS (Illumina) HFD-PGW group vs. HFD-C group:
reduced Bacteroidetes/Firmicutes ratio in HFD-C group mitigated in HFD-PGW group;
rel. increase: Proteobacteria, Bacteroidaceae, Rikenellaceae, S24-7, Desulfovibrionaceae, Enterobacteriaceae; rel. decrease:
Deferribacteres, Lachnospiraceae, Ruminococcaceae, Peptococcaceae		 - - [161]
Polygonatum sibiricum, radix ethanolic extract (70%) with a saponin yield of 3.07 ± 0.02 mg/g (PSS) 6 groups:
non-diabetic control,
diabetic model control (DMC, HFD-streptozotocin induced), metformin-positive control group (MPC), LPT (1 g/kg PSS), MPT (1.5 g/kg PDD), HPT (2 g/kg PSS)		 male ICR mice (6 weeks, weight 20 ± 1.5 g) treated for 5 weeks, fecal samples were collected during week 5 agar plate counting using fecal bacteria selective agars LPT, MPT, HPT groups vs. DMC group:
number of probiotics in the feces increased significantly (p < 0.01), especially Bifidobacterium; the number of harmful bacteria (Enterococcus, Enterobacteriaceae) decreased 		- - [164]
Rhodiola rosea, radix root extract (SHR-5) two groups:
control group (yeast solution); SHR-5 group (25 mg/mL SHR-5 + yeast solution)		 Oregon-R flies treated throughout the lifespan of the flies; flies were homogenized in PBS for microbiome analyses V6–V8 region of 16S rRNA gene, NGS (Illumina); bacterial growth plates SHR-5 group:
increase in Acetobacter; decrease in Lactobacillales; SHR-5 decreased the total culturable bacterial load of the fly gut while increasing the overall quantifiable bacterial load		 - - [167]
Salvia rosmarinus, folium rosemary extract (RE) containing 60% carnosic acid 3 groups: control; chronic restraint stress (CRS) group; CRS + RE (100 mg/kg) (n = 12 per group) male adult ICR mice treated for 21 days; fecal samples collected (timepoint not indicated) V1–V3 region of 16S rRNA gene, NGS (Illumina) CRS+RE group: reversed intestinal microbiota composition of CRS group; rel. increase Firmicutes and Lactobacillus; rel. decrease Bacteroidetes and Proteobacteria - - [42]
Schisandra chinensis, fructus total ethanolic extract (95%) (SCE), lignan fraction (SCL), polysaccharide fraction (SCPS), volatile oil (SCVO) 6 groups:
control, lipopolysaccharide (LPS)-induced inflammation, SCE (1.2 g/kg) + LPS, SCL (500 mg/kg BW) + LPS, SCPS (300 mg/kg) + LPS, SCVO (150 mg/kg BW) + LPS (n = 10 per group)		 C57BL/6 mice (18–22 g) treated for 14 days; fecal samples collected after behavioral tests V3–V4 region of 16S rRNA gene, NGS (Illumina) SCE and SCL-treated group:
LPS-induced increase in Bacteroidetes and decrease in Firmicutes alleviated
rel. increase: Lactobacillus; rel. decrease: Bacteroides 		SCFA analysis by GC-MSTQ8040 SCE and SCL-treated group:
increased levels of butyric acid and propionic acid		 [173]
dried, powdered fruits (SC); wine- processed fruits (WSC); main SC and WSC constituent: lignans 4 groups:
control (0.9% saline); chronic unpredictable stress procedure (CUSP) group; CUSP + SC (280 mg/kg BW); CUSP + WSC (280 mg/kg BW)
(n = 6 per group)		 male Sprague Dawley rats (180–220 g) treated for 5 weeks; fresh fecal samples collected on day 30 V3–V4 region of 16S rRNA gene, NGS; (Illumina) CUSP+SC/WSC vs. CUSP:
increased rel. abundance of Lachnospiraceae; rel. decrease in Bacteroides 		lactate analysis in the intestine by ELISA reduction: D- and L-lactate [172]
water extract (SCW) two groups:
placebo (n = 15);
SCW (n = 13)
2 pouches in a day, equivalent to 6.7 g of dried S. chinensis fruits		 female obese volunteers BMI ≥ 25 kg/m2 feces samples collected at the beginning and the end of treatment denaturing gradient gel electrophoresis; qPCR with specific primers SCF group vs. placebo:
increase: Akkermansia, Roseburia, Bacteroides, Prevotella, Bifidobacterium;
decrease: Ruminococcus 		- [174]
S. chinensis polysaccharide extract (total carbohydrate content: 94.9%) (SCP) 4 groups:
normal control (saline), model group (DSS-induced colitis), DSS+ positive control (salazosulfapyridine), DSS + SCP (8.0 g/kg BW)
(n = 8 per group)		 male C57BL/6J mice (20 ± 2 g, 8–10 weeks old) treated for 3 weeks 16S rRNA gene, NGS (Illumina) SCP vs. DSS group: Firmicutes, Proteobacteria, and Bacteroidetes returned to normal relative abundances; rel. increase: Alloprevotella, Saccharibacteria, Bacteroidetes Bacteroidales_S24_7_group family; rel. decrease: Anaerotruncus, Firmicutes SCFA analysis by GC-MS SCP vs. DSS group:
recovery/increase in propionic acid, butyric acid, valeric acid		 [175]
Trigonella foenum-graecum, semen ground seeds (2% of the diet by weight)
(FS)		 4 groups:
HFD; HFD + FG; control diet (CD); CD + FG
(n = 20 per group)		 male C57BL/6J mice (9 weeks old) treated for 16 weeks; fecal samples collected after euthanasia V4 region of 16S rRNA gene, NGS (Illumina) CD ± FS and HFD ± FS: shifts in alpha and beta diversity compared to non-FS groups; diversity and significantly increased alpha diversity; FS mitigated dysbiotic effects of HFD - - [177]
fenugreek seeds (28% galactomannan and 0.672% apigenin-7-glycoside)
FS		 2 groups:
control (n = 11); FS (n = 10, 1.5 g fenugreek seeds/kg BW)		 male castrated piglets (Duroc × Piétrain; 8.26 kg) treated for 28 days; stomach, distal jejunum, ileum, cecum, and colon contents removed after sacrifice qPCR with specific primers increase: Lactobacillus group, L. johnsonii, Clostridium cluster I, L. reuteri
decrease: Escherichia/Hafnia/Shigella group
Clostridium cluster YIV remained stable		 lactate (HPLC), SCFAs (GC-FID) FS vs. control group:
increased colonic butyric acid levels; increased L-lactic acid levels in the small intestinal digesta		 [178]
Vitis vinifera, fructus lyophilized table grape mixture of red-, green-, and black-seeded and seedless grapes
(G)		 5 groups:
low fat (LF; 10% of energy from fat); high fat (HF; 34% of energy from fat) plus 3% G (w/w; HF-3G); HF plus 3% sugar (w/w; HF-3S); HF plus 5% G (HF-5G); HF plus 5% sugar (HF-5S) (n = 10 per group)		 male C57BL/6J mice (4 weeks old) treated for 11 weeks; colonic mucosa and digesta from duodenum, jejunum, cecum, proximal and distal colon collected after sacrifice qPCR with primers targeting 16S rRNA gene of specific bacterial genera; V3–V4 region of 16S rRNA, Illumina sequencing decreased alpha diversity in HF-5G and HF-5S group compared to HF-3G group;
increase in Allobaculum in LF and HF-3G group; tendency to increase in Akkermansia muciniphila in HF-3G and HF-5G group;
decrease in Desulfobacter spp. in HF-3G group		 - - [197]
phenolic compound-rich grape pomace extract (70% ethanol; 920 mg/g phenolic compounds) (PC) 5 groups:
PC 2.5 (2.5 mg/kgBW/d); PC 5 (5 mg/kg BW/d); PC 10 (10 mg/kg BW/d); PC 20 (20 mg/kg/d); control group (0.1% DMSO) (n = 6 per group)		 male adult Wistar rats (2 months old) treated for 14 months; fecal samples collected at baseline, and after 6 and 14 months of treatment qPCR with primers targeting 16S rRNA gene of specific bacterial genera and universal primer for total bacteria increase in Bifidobacterium in PC 2.5 and PC 5 groups after 6 and 14 months compared to control and young rats; PC (all groups) abolished increase in Clostridium (cluster 1) after 14 months occurring in control - - [194]
grape antioxidant dietary fiber (GADF) 2 groups:
control diet; GADF diet (50 g/kg) (n = 10 per group)		 male Wistar rats (body weight of 215 ± 2 g) treated for 4 weeks; cecal content collected after sacrifice qPCR with primers targeting 16S rRNA gene of specific bacterial genera GADF group:
increase:
Lactobacillus spp.
decrease:
Bifidobacterium spp.		 - - [195]
grape seed and grape marc meal extract (GSGME) 3 groups:
control group (basal diet BD); GSGME group (BD with 1% GSGME) (n = 16 per group)		 crossbreed pigs (5 weeks old) treated for 4 weeks; fecal samples collected after sacrifice qPCR with primers targeting 16S rRNA gene of specific bacterial genera decrease in Streptococcus in GSGME group volatile fatty acid analysis by GC with FI detector Decrease in acetic acid, propionic acid, and valeric acid in GSGME group [196]
grape extract (GE) 3 groups:
standard diet (LFD, 3.85 kcal g−1, 10% energy from fat); high-fat +high-fructose diet (HFFD, 4.73 kcal g−1, 22% fructose + 22% lard); HFFD + 1% w/w GE diet (HFFD + GE) (n = 12 per group)		 male C57BL/6Cnc mice (4 weeks old) treated for 13 weeks; fecal samples were collected after sacrifice V3–V4 region of 16S rRNA gene, NGS GE group: increased gut microbiota diversity, Firmicutes/Bacteroidetes ratio, rel. increase in Verrucomicrobia, Bifidobacteria, Akkermansia, Clostridia;
rel. decrease in Bacteroidetes, Proteobacteria, Desulfovibrio, and Bacteroides 		- - [199]
lyophilized table grape mixture (red-, green-, and black-seeded and seedless) (GP); extractable polyphenol-rich fraction (EP) (180 mg/g total phenolics); nonextractable, polyphenol-poor fraction (NEP) (10.5 mg/g total phenolics) 6 groups:
low fat (LF; 10% of energy from fat); high fat (HF; 44% of energy from fat); HF plus extractable polyphenol-rich fraction (HF-EP); HF plus nonextractable, polyphenol-poor fraction (HF-NEP); HF plus extractable and nonextractable polyphenol fraction (HF-EP + NEP); HF plus 5% powdered grapes (HF-GP) (n = 10 per group)		 male C57BL/6J mice (4 weeks old) treated for 16 weeks; cecal mucosa and digesta samples collected after sacrifice V4–V5 region of 16S rRNA gene, NGS (Illumina) of cecal mucosa samples HF-GP vs. HF control:
rel. increase in microbiota diversity compared to HF control group
HF-EP vs. HF-control:
rel. increase in Lachnospiraceae
HF-NEP vs. HF-control:
rel. increase in Coprococcus
HF-EP+NEP vs. HF-control:
rel. increase in Lachnospiraceae and Coprococcus; rel. decrease in Ruminococcus and Mogibacteriaceae		 SCFA analysis in cecal digesta by GC-MS-MS HF-GP vs. HF-EP + NEP group:
increase in the SCFAs acetate, propionate, and butyrate
HF-EP + NEP vs. HF control group:
decrease in cecal acetate		 [198]
sun-dried raisins 1 group:
three servings per day of 28.3 g raisins (90 cal, 2 g dietary fiber) (n = 13)		 healthy volunteers (ages 18–59 years) treated for 2 weeks; fecal samples collected before the start of raisin consumption, on day 7 and day 14 V1–V2 region of 16S rRNA gene, NGS (Illumina) weeks 1 and 2 vs. day 0:
rel. increase in
Ruminococcaceae;
Faecalibacterium prausnitzii, and Bacteroidetes longum
rel. decrease in
Bifidobacterium spp., Klebsiella spp., Prevotella spp.		 - - [192]
red grape pomace (GP) extract (Eminol®) 1 group:
two capsules of GP extract per day (1400 mg GP/day) (n = 10)		 healthy female volunteers (ages 25–65 years; BMI < 25 kg/m2) treated for 21 days; fecal samples collected after washout period, on day 14 and on day 21 of GP consumption qPCR with primers targeting specific bacterial genera no change in the intestinal microbiota composition phenolic metabolite analysis by UPLC-ESI-MS/MS; short- and medium-chain fatty acid analysis by SPME-GCMS day 0 vs. day 7 or 14:
SCFA:
increase in total SCFAs and propionic acid (14 and 21 days); increase in acetic acid (14 days)
MCFA:
decrease in pentanoic, hexanoic, and octanoic acids;
fecal phenolic metabolites:
increase in 3-(4′-hydroxyphenyl)-propionic acid		 [200]
Vitis vinifera, semen grape seed tannins:
monomer fraction (GSM);
polymer fraction (GSP)		 3 groups:
control group (standard diet), GSM group (standard diet + GSM 71 mg/kg diet), GSP (standard diet + GSP, 71 mg/kg diet) (n = 6 per group)		 male Sprague Dawley rats (145 g) treated for 12 weeks; cecal contents were collected after sacrifice - - cecal volatile fatty acid (SCFA) analysis by GC GSP vs. control:
increase in total VFAs, acetate, propionate, and butyrate
GMP vs. control:
increase in acetate, decrease in butyrate		 [184]
grape seed extract (GSE) 1 group:
standard diet (SD, 2 kg per day), treatment diet (SD plus 1% w/w GSE) (n = 6)		 crossbred female pigs (130–150 kg) duration 12 days; SD for 3 days, SD+GSE for 6 days, post-treatment SD for 3 days; fecal samples collected daily V3–V4 region of 16S rRNA gene NGS (Illumina) before vs. during GSE:
increase in Lachnospiraceae, unclassified Clostridales, Lactobacillus, and Ruminococcus 		phenolic metabolite analysis by HPLC-MS before vs. during GSE:
increase in 4-hydroxyphenylvaleric acid and 3-hydroxybenzoic acid		 [185]
grape seed meal (GSM) 4 groups:
control group (standard diet, SD); AFB1 group (SD + 320 µg/kg aflatoxin B1, AFB1); GSM group (SD+ 8% GSM); AFB1 + GSM group (SD + 32 µg/kg AFB1 + 8% GSM) (n = 6 per group)		 healthy weaned crossbred TOPIGS-40 hybrid piglets (9.13 ± 0.03 kg) treated for 30 days; colon contents collected after sacrifice V3–V4 region of 16S rRNA gene NGS GS vs. control:
rel. increase in Bacteroidetes, Proteobacteria, Prevotella, Megasphaera, Clostridiales, and Anaerovibrio; rel. decrease in Firmicutes, Lactobacillus, and Lachnospiraceae		 - - [186]
grape seed meal (GSM) 4 groups:
control group (standard diet, SD); DSS colitis group (SD + DSS 1 g/kg BW); GSM group (SD + 8% GSM); DSS+GSM group (SD + 8% GSM + DSS 1 g/kg BW) (n = 5–6 per group)		 weaned crossbred TOPIGS-40 hybrid piglets (9.13 ± 0.03 kg) treated for 30 days; descending colon contents collected after sacrifice V3–V4 region of 16S rRNA gene NGS (Illumina) rel. increase in Proteobacteria and rel. decrease in Lactobacillus in DSS, GSM, and DSS + GMS group; rel. increase in Megasphaera and Anaerovibrio in GSM and DSS+GSM groups; rel. decrease in Roseburia in GSM and DSS + GSM groups SCFA analysis by GC-FID increase in butyric acid and valeric acid, and decrease in acetic acid by GSM [187]
GSE
Leucoselect® (proanthocyanidin content >80%)		 3 groups:
sham-operated group (standard diet, SD); OVX group (SD); OVX + GSE group (GSE diet, 10 g GSE/5 kg diet) (n = 5 per group)		 female C57BL/6J mice (7 weeks old) treated for 8 weeks; fecal samples were collected 8 weeks after surgery qPCR with group-specific primers targeting 16S rRNA of total bacteria, Firmicutes, and Bacteroidetes OVX + GSE vs. OVX group:
increase in Bacteroidetes; decrease in Firmicutes and Firmicutes/Bacteroidetes ratio		 - - [188]
GSE Vitaflavan® (procyanidin content 75.6%) 4 groups:
control LFD (10% kcal from fat, CD); HFD (45% kcal from fat); HFD + 0.07 g GSE/4057 kcal (HF10); HFD + 0.70 g GSE/4057 kcal (HF100) (n = 8 per group)		 male C57BL/6J mice (9 weeks old) treated for 16 weeks; small intestine, cecum, and colonic tissue collected after sacrifice V4 region of 16S rRNA gene NGS (Illumina) of mucosal-adherent metabolically active bacteria (results converted to 16S cDNA values; HF 100 group not analyzed) HF10 group vs. HFD:
small intestine: decrease in Firmicutes, Bacteroides-Prevotella spp., and Parabacteroides spp.; increase in Bacteroidetes and Bifidobacterium spp.		 - - [189]
proanthocyanidin-rich GSE 1 group, 3 treatments:
0.5 g GSE/day (0.19 g/day/subject as proanthocyanidin); 0.5 g green tea extract/day; 0.5 g champignon extract/day		 9 healthy male adults (ages 37–42 years) duration 10 weeks; 6 periods: 14-day washout period, three 14-day administration periods interrupted by two 14-day washout periods; fecal samples collected on days 0, 2, 7, and 14 of administration bacterial plate counting GSE, day 14 vs. day 0:
increase in Bifidobacterium; tendency to decrease in Enterobacteriaceae		 fecal putrefactive product analysis by GC; ammonium analysis by HPLC GSE, day 14 vs. day 0:
tendency to decrease in skatol, indole, 4-ethylphenol, p-cresol, phenol, and ammonia after grape seed extract administration		 [190]