γ-PGA-Rich Chungkookjang, Short-Term Fermented Soybeans: Prevents Memory Impairment by Modulating Brain Insulin Sensitivity, Neuro-Inflammation, and the Gut-Microbiome-Brain Axis

Abstract

Fermented soybean paste is an indigenous food for use in cooking in East and Southeast Asia. Korea developed and used its traditional fermented foods two thousand years ago. Chungkookjang has unique characteristics such as short-term fermentation (24-72 h) without salt, and fermentation mostly with Bacilli. Traditionally fermented chungkookjang (TFC) is whole cooked soybeans that are fermented predominantly by Bacillus species. However, Bacillus species are different in the environment according to the regions and seasons due to the specific bacteria. Bacillus species differently contribute to the bioactive components of chungkookjang, resulting in different functionalities. In this review, we evaluated the production process of poly-γ-glutamic acid (γ-PGA)-rich chungkookjang fermented with specific Bacillus species and their effects on memory function through the modulation of brain insulin resistance, neuroinflammation, and the gut-microbiome-brain axis. Bacillus species were isolated from the TFC made in Sunchang, Korea, and they included Bacillus (B.) subtilis, B. licheniformis, and B. amyloliquefaciens. Chungkookjang contains isoflavone aglycans, peptides, dietary fiber, γ-PGA, and Bacillus species. Chungkookjangs made with B. licheniformis and B. amyloliquefaciens have higher contents of γ-PGA, and they are more effective for improving glucose metabolism and memory function. Chungkookjang has better efficacy for reducing inflammation and oxidative stress than other fermented soy foods. Insulin sensitivity is improved, not only in systemic organs such as the liver and adipose tissues, but also in the brain. Chungkookjang intake prevents and alleviates memory impairment induced by Alzheimer's disease and cerebral ischemia. This review suggests that the intake of chungkookjang (20-30 g/day) rich in γ-PGA acts as a synbiotic in humans and promotes memory function by suppressing brain insulin resistance and neuroinflammation and by modulating the gut-microbiome-brain axis.

Keywords: Bacillus; cheonggukjang; chungkookjang; glucose metabolism; gut microbiota; memory function; soybean.

Figure 1

The metabolomic analysis of traditionally made chungkookjang (TFC) and chungkookjang fermented with Bacillus licheniformis (SFC). (A) Soybeans fermented for 0 to 60 h with TFC and SFC, and the separation of bioactive components in the unfermented and fermented soybeans by partial least squares-discriminant analysis (PLS-DA) [7]. (B) Heatmap of bioactive components of soybeans fermented with Bacillus licheniformis for 0, 12, 24, 36, 48, and 60 h [7]. LPC, lysophosphatidylcholine; PC, phosphatidyl choline; Ser, serine; Pro, proline, Glu, glutamic acid; Leu, leucine, Thr, threonine; Tyr, tyrosine; Val, valine; DDMP, 2,3-Dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one; Phe, phenylalanine.

Figure 2

Potential action mechanism of chungkookjang in glucose metabolism and memory function. ANS, autonomous nervous system; HPA, hypothalamus–pituitary–adrenal; SCFA, short-chain fatty acids. Chungkookjang components directly influence glucose metabolism in the liver and brain, and they also indirectly affect them through the gut–microbiome–liver–brain axis. The improvement of glucose metabolism in the hippocampus reduces amyloid-b deposition, which decreases memory impairment. Thus, chungkookjang intake (about 20–30 g/day) protects against and partially alleviates type 2 diabetes, Alzheimer’s disease, and post-stroke symptoms.