Lactate-Fortified Puerariae Radix Fermented by Bifidobacterium breve Improved Diet-Induced Metabolic Dysregulation via Alteration of Gut Microbial Communities

Abstract

Background: Puerariae Radix (PR), the dried root of Pueraria lobata, is reported to possess therapeutic efficacies against various diseases including obesity, diabetes, and hypertension. Fermentation-driven bioactivation of herbal medicines can result in improved therapeutic potencies and efficacies. Methods: C57BL/6J mice were fed a high-fat diet and fructose in water with PR (400 mg/kg) or PR fermented by Bifidobacterium breve (400 mg/kg) for 10 weeks. Histological staining, qPCR, Western blot, and 16s rRNA sequencing were used to determine the protective effects of PR and fermented PR (fPR) against metabolic dysfunction. Results: Treatment with both PR and fPR for 10 weeks resulted in a reduction in body weight gain with a more significant reduction in the latter group. Lactate, important for energy metabolism and homeostasis, was increased during fermentation. Both PR and fPR caused significant down-regulation of the intestinal expression of the MCP-1, IL-6, and TNF-α genes. However, for the IL-6 and TNF-α gene expressions, the inhibitory effect of fPR was more pronounced (p < 0.01) than that of PR (p < 0.05). Oral glucose tolerance test results showed that both PR and fPR treatments improved glucose homeostasis. In addition, there was a significant reduction in the expression of hepatic gene PPARγ, a key regulator of lipid and glucose metabolism, following fPR but not PR treatment. Activation of hepatic AMPK phosphorylation was significantly enhanced by both PR and fPR treatment. In addition, both PR and fPR reduced adipocyte size in highly significant manners (p < 0.001). Treatment by fPR but not PR significantly reduced the expression of PPARγ and low-density lipoproteins in adipose tissue. Conclusion: Treatment with fPR appears to be more potent than that of PR in improving the pathways related to glucose and lipid metabolism in high-fat diet (HFD)+fructose-fed animals. The results revealed that the process of fermentation of PR enhanced lactate and facilitated the enrichment of certain microbial communities that contribute to anti-obesity and anti-inflammatory activities.

Beneficial Effects of Newly Isolated Akkermansia muciniphila Strains from the Human Gut on Obesity and Metabolic Dysregulation

“…Several studies on animals suggest that the consumption of a high-fat diet (HFD) alters the gut microbial communities. Such an event may eventually manifest augmented intestinal permeability as a result of the gut barrier disintegration, leading ultimately to the development of metabolic endotoxemia, inflammation and metabolic disorders [ 10 , 11 , 12 , 13 ]. Therefore, controlling gut microbial composition may be a therapeutic strategy for the prevention and treatment of obesity.…”

Traditional Chinese medicine, liver fibrosis, intestinal flora: is there any connection?—a narrative review

“…Lobata reduces the expression of inflammatory factors, such as TNF-α and IL-6. The expression levels of these inflammatory factors after Bifidobacterium fermentation when using P. Lobata were shown to be significantly lower than those in Pueraria without fermentation (22). Also, in the small intestine and colon of mice fed with a high-fat diet, puerarin, a functional extract of P. Lobata, was shown to block the expression of the proinflammatory factors IL-6 and monocyte chemoattractant protein-1 and increase the expression of the anti-inflammatory factor IL-10 (23).…”

Effects of Live and Pasteurized Forms of Akkermansia from the Human Gut on Obesity and Metabolic Dysregulation

“…For PCR amplification, the following conditions were maintained: an initial denaturation step at 95 • C for 10 min followed by 40 cycles of amplification involving denaturation at 95 • C for 10 s, annealing at 55-58 • C for 5 s and extension at 72 • C for 10 s. The obtained PCR data were processed and analyzed using the dedicated Light Cycler software (version 1.2, Roche Applied Science) and normalized using glyceraldehyde-3-phosphatase dehydrogenase (GAPDH) as the housekeeping gene. The relative expression levels of the genes were measured, as described previously [16,19,26].…”

“…Several animal studies reported that the consumption of a HFD modulates the gut microbial population. Such changes may enhance intestinal permeability due to gut-barrier disintegration, ultimately leading to the onset and development of metabolic endotoxemia, inflammation and metabolic disorders [16][17][18][19]. Therefore, regulating the gut microbial population via microbiome-based treatments, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), metabolic surgery and drugs, may represent an effective targeted therapeutic strategy for the prevention and treatment of metabolic syndromes [12].…”