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. 2021 Jul 22;10(8):1162. doi: 10.3390/antiox10081162

Table 3.

Blueberries gut modulatory and prebiotic effects in T2DM or metabolic syndrome animal models.

Animal Model Source/Dose Duration Main Outcomes Ref
HFD-fed C57BL/6J mice BB polyphenol extract (200 mg/kg) 12 weeks Prevotella and Clostridium
Lactobacillus spp. and Coprobacillus
Proteobacteria and Helicobacter
Bifidobacterium
[34]
HFHS diet-fed male C57BL/6J mice BB polyphenol extract (200 mg/kg) 8 weeks ↑ Glucose tolerance
↑ Colonic mucus thickness
Ruminococcaceae and Peptostreptococcaceae
Bacteroidetes phylum
= Akkermansia muciniphila
Adlercreutzia equolifaciens
[162]
BB oligomeric proanthocyanidins fraction (53 mg/kg) 8 weeks ↑ Glucose tolerance
↑ Colonic mucus thickness
Akkermansia muciniphila
Adlercreutzia equolifaciens
Ruminococcaceae and Peptostreptococcaceae
HFD-fed male C57BL/6J mice and diabetic male C57BL/KsJ db/db mice BB phenolic extract (5 g/L in drinking water) 14 weeks ↓ BW gain and adiposity
↑ Glucose tolerance and insulin sensitivity
↓ Plasma LPS, IL-6, TNF-α contents
↓ Hepatic steatosis
↓ Plasmatic and hepatic TGs
↓ Serum LDH, ALT and AST
↑ Intestinal MUC-2 levels
↑ Intestinal occludin and ZO-1 mRNA expression
↓ Intestinal and hepatic inflammation (TLR4, IL-6, TNF-α)
Bifidobacteria and Akkermansia
Desulfovibrio and Bilophila genera
↓ Plasma BA pool size
↑ mRNA and protein expression of FXR and TGR5
↓ mRNA expression levels of SREBP-1c and ChREBP and downstream genes
[33]
HFD-fed male Sprague Dawley rats Dietary fiber from BB (7% of diet) 8 weeks ↓ BW gain
↓ Serum T-Chol levels
↓ Hepatic steratosis
↓ Hepatic mRNA expression of SCD1
= Hepatic mRNA expression of genes involved in lipogenesis and β-oxidation
↑ mRNA expression of Ucp-1
↑ Fecal and serum total SCFAs
↑ Butyrate-producing bacteria
↑ Actinobacteria and Proteobacteria
↓ Firmicutes and ↑ Bacteroidetes
= Bifidobacterium
[163]
HFHS diet-fed male C57BL/6 mice Freeze dried BB powder (4% of diet, 160 mg/day) 12 weeks = BW and liver weight
= HOMA-IR
= Glucose homeostasis
= Hepatic TGs, T-Chol
= Plasma ALT and AST
↓ Fecal BCFA isobutyric and isovaleric acid
Ruminococcus, Lachnospiraceae and Blautia
[152]
BB proanthocyanidin extract (1 mg/day) 12 weeks ↓ BW and epididymal adipose tissue weight
↓ Plasma insulin and C-peptide levels
↓ HOMA-IR
↑ Insulin sensitivity
= Hepatic TGs, T-Chol
= Plasma ALT and AST
↓ BCFA isobutyric and isovaleric acid
Muribaculum inestinale abundance
↑ Oxidative phosphorylation pathway
↑ Homeostasis and insulin sensitivity after transferred by FMT
HFD-fed Wistar rats Freeze-dried BB powder (10% of diet 8 weeks = BW
↑ Insulin sensitivity
↓ Serum LBP levels
↓ Hepatic p-IRS1 to IRS1 ratio
↓ Hepatic MDA concentration
↑ Ileal mRNA expression of Muc-2
↓ Ileal mRNA expression of TNF-α
↑ Goblet cell number per crypt
↑ Gammaproteobacteria (Actinobacillus and Aggregatibacter)
Lactobaccilus
↓ Firmicutes and Bacteroidetes
↑ Serum SCFAs (acetate and propionate)
↑ Ileal mRNA expression of GLP-1
[127]
HFD-fed C57BL/6J mice Fermented BB juice and fresh BB juice 17 weeks ↑ Cecum SCFAs (acetate and valerate)
↑ Bacteroidetes (Barnesiella)
↓ Firmicutes
Akkermansia, Bifidobacterium, and Lactobacillus
↓ Obese-type gut microbiota (Oscillibacter and Alistipes)
[156]

BA, bile acids; BCFA, branched chain fatty acids; FMT, fecal microbiota transplant; FXR, farnesoid X receptor; GLP-1, glucagon-like peptide-1; HFD, high-fat diet; HFHS, high-fat high sucrose; IRS-1, insulin receptor substrate-1; LBP, lipopolysaccharide-binding protein; LDH, lactate dehydrogenase; LPS, lipopolysaccharides; Muc-2, mucin 2; SCFAs, short chain fatty acids; TGR5, G-protein-coupled bile acid receptor; TLR4, Toll-like receptor 4; Ucp-1, uncoupling protein-1; ZO-1, zonula occludens-1; ↑, increased; ↓, decreased; =, unchanged.