Fermented soybean foods and diabetes

Abstract

The number of patients with type 2 diabetes mellitus is increasing, and its prevention and management are important. One of the factors contributing to the increased incidence of type 2 diabetes mellitus is the change in dietary habits, including a Westernized diet. Fermented foods are foods that are transformed by the action of microorganisms to produce beneficial effects in humans and have been consumed for thousands of years. The production and consumption of fermented soy foods, including natto, miso, douchi, cheonggukjang, doenjang, tempeh, and fermented soy milk, are widespread in Asian countries. This review focuses on fermented soybean foods and summarizes their effects on diabetes. Fermentation increases the content of ingredients originally contained in soybeans and adds new ingredients that are not present in the original soybeans. Recent studies have revealed that fermented soybean food modifies the gut microbiota‐related metabolites by modifying dysbiosis. Furthermore, it has been reported that fermented soybean foods have antioxidant, anti‐inflammatory, and anti‐diabetic effects. In recent years, fermented foods, including fermented soybeans, have shown various beneficial effects. Therefore, it is necessary to continue focusing on the benefits and mechanisms of action of fermented foods.

The number of patients with type 2 diabetes mellitus is increasing, and its prevention and management are important. Fermented soybean food modifies the gut microbiota‐related metabolites by modifying dysbiosis. Fermented soybean foods also have antioxidant, anti‐inflammatory, and anti‐diabetic effects.

INTRODUCTION

Type 2 diabetes is a major determinant of mortality, with an increasing prevalence worldwide ¹ . In 2021, 537 million individuals were living with diabetes ² . Therefore, the prevention and management of type 2 diabetes is an important public health concern.

Several dietary factors are reportedly involved in the pathogenesis of type 2 diabetes, including insulin secretion capacity, insulin resistance, fatty liver disease, inflammation, gut microbiota, and weight gain ¹ . Although studies with high‐quality evidence are still lacking, Westernized diets, such as insufficient whole grains, excess refined rice and wheat, processed meats, and unprocessed red meats, are known to be associated with the development of type 2 diabetes ³ , ⁴ .

Fermented foods are foods transformed by the action of microorganisms to produce beneficial effects in humans ⁵ . Historically, many foods, including meat, fish, dairy products, vegetables, soybeans, legumes, grains, and fruits, have undergone fermentation. The production and consumption of fermented soybean foods are widespread in Asian countries. The main fermented soybean foods include natto, miso, douchi, cheonggukjang, doenjang, tempeh, and fermented soy milk ⁶ , ⁷ . Recent research has shown that fermentation can be applied to improve the health benefits of the bioactive components in soybeans. This review focuses on fermented soybean foods and summarizes their effects on diabetes.

NUTRITION CHANGE OF SOYBEAN DURING FERMENTATION

Raw soybeans contain dietary fibers, phospholipids, and isoflavones (genistein and daidzein), phenolic acids, saponins, trypsin inhibitors, and phytic acids.

The differences in fermented soybean foods are mainly due to the microorganisms used, with some using only bacteria, mainly Bacillus, for fermentation and others using only filamentous fungi, mainly Aspergillus, and often both of these microbial groups. For example, natto, kinema, and cheonggukjang use only bacteria; douchi, tempeh, miso, and tofu use only filamentous fungi; and doenjang uses both ⁶ . Fermentation improves soybean quality by increasing the digestibility, nutrition, and isoflavone content ⁸ . Fermentation increases the nutritional value of soybeans by increasing the content of vitamins, essential amino acids, and fatty acids and by enhancing detoxification. In addition to proteins and isoflavones, soybean contains numerous functional and nutritional substances. Microorganisms with the ability to produce specific hydrolytic enzymes play an important role in enhancing their functional properties ⁸ , ⁹ , ¹⁰ . The modification of isoflavones is carried out by β‐glucosidase; therefore, the amount of aglycone isoflavones depends on the amount of β‐glucosidase ¹¹ , ¹² . Aglycone isoflavones, such as genistein and daidzein, are deglycosylated by intestinal hydrolytic enzymes and microbial glycosidases, leading to an increase in their bioactive potential ¹³ . In addition, fermentation by various microorganisms can improve the antioxidant capacity and the levels of vitamin B2, vitamin B12, vitamin K2, and gamma aminobutyric acid ⁷ , ¹⁴ , ¹⁵ . Angiotensin‐converting enzyme inhibitory peptides are produced by the breakdown of soy protein ¹⁶ . Furthermore, several nutritional changes have been reported to result from soy fermentation, including increased total soluble iron, folate levels, tocopherol composition, and β‐, γ‐, and δ‐tocopherol levels ¹⁷ .

Miso

Miso, which is a traditional Japanese spice used to add flavor to soups and dishes, is a fermented soybean paste malted with ‘koji’, produced from Aspergillus oryzae. There are various types of miso depending on the koji used, including rice miso, which is made by adding rice koji to soybeans, barley miso, which is made by adding barley koji to soybeans, and soybean miso, which uses only soybeans. As with other fermented soybean foods, the characteristics of miso vary with ingredients, temperature, fermentation time, salt concentration, and the strain of A. oryzae used. It has been reported that amino acids such as glutamic acid, aspartic acid, and proline are included during the aging process of miso ¹⁸ , ¹⁹ .

Natto

Natto is one of the traditional Japanese fermented soybean foods. Among several varieties of natto, natto fermented with Bacillus subtilis is the most well known. It has been reported that during the fermentation process, proteins are cleaved by extracellular proteases produced by Bacillus natto, increasing the free amino acid content by 10–30%. Proteins derived from natto consist of at least 17 amino acids, including glutamic acid, glutamine, aspartic acid, leucine, proline, serine, lysine, methionine, threonine, glycine, isoleucine, tyrosine, phenylalanine, histidine, arginine, alanine, and valine ²⁰ , ²¹ . The characteristics of natto vary with the steaming time, relative humidity, fermentation time, and temperature ²² .

Cheonggukjang

In Korea, the various types of fermented soybeans are collectively called ‘jang’. Cheonggukjang is a traditional Korean fermented soybean food made from fermented boiled soybean rice straw. Cheonggukjang does not contain salt, but ingredients such as crushed green onions, garlic, and chili powder are added for flavor ²³ . Various enzymes secreted by bacteria during fermentation have been reported to break down soybean hulls, cell membrane fibers, and intracellular sugars and proteins, improving digestibility and increasing free amino acid content, vitamin B2 and vitamin K₂ ²³ . In addition, Cheonggukjang is reported to have higher protein and fat content than doenjang ²⁴ .

Doenjang

Doenjang is a traditional Korean miso, made by fermenting boiled soybeans (meju) in salted water using yeast (A. oryzae) and Bacillus (Bacillus) to break down soybean proteins to produce organic acids, amino acids, and minerals ²⁵ .

Kochujang

Kochujang is a mixture of meju powder, koji powder, and chili powder, which is fermented and aged for at least 6 months ²⁶ . Kochujang contains a higher carbohydrate source than Doenjan and may contain a variety of Bacillus spp ²⁶ .

Douchi

Douchi is a Chinese fermented soybean food that has been used as a protein source and seasoning. Douchi is produced from two stages: pre‐fermentation, which consists of an aerobic process using several microorganisms, such as A. oryzae, Zygosaccharomyces rouxii, Lactobacillus plantarum, and B. subtilis, and post‐fermentation where salt and spices are added and mixed together for anaerobic fermentation ²⁷ , ²⁸ .

Fermented soy milk

Fermented soy milk is a traditional Chinese vegetable protein drink, rich in bioactive substances such as saponins, polyphenols, isoflavones, and phytosterols in addition to soy nutrients ²⁹ .

Tempeh

Tempeh is a food indigenous to Indonesia and has been consumed as a staple protein source ³⁰ . Tempeh is usually made from soybeans fermented with Rhizopus oligoporus fungal species ³¹ . The microbial composition of tempeh varies depending on the variation in its production. Fermentation of soybeans is a source of large amounts of protein, vitamin B12, and bioactive compounds, along with reduced concentrations of protease inhibitors, phytic acid, and phenols, which are anti‐nutritional factors found in raw soybeans ³² , ³³ .

Kinema

Kinema is a traditional non‐salted fermented soybean food prepared in the eastern hills of Nepal, the Darjeeling hills, and Sikkim in India ³⁴ . To make traditional kinema, soybeans are washed, soaked in water overnight, boiled for about 90 min, ground, wrapped in fern leaves and sack cloth, and fermented in a warm place for several days to 3 days. Bacillus subtilis is solely responsible for kinema production.

Kinema is rich in all essential amino acids with processing with B. subtilis leading to a 60‐fold increase in the free amino acid content of soybeans ³⁵ .

EFFECTS OF FERMENTED SOYBEAN FOODS ON GUT MICROBIOTA

The role of gut microbiota in type 2 diabetes has been reported in recent years. Among the commonly reported genera, Bacteroides, Bifidobacterium, Roseburia, Faecalibacterium, Akkermansia, Lactobacillus, Ruminococcus, Fusobacterium, and Blautia have been associated with type 2 diabetes ³⁶ . Metabolites produced by gut microbiota have been reported to have many functions, including energy conversion, signal transduction, epigenetic effects, and coenzyme activity, and are thought to be associated with diabetes ³⁷ . However, it has been reported that the gut microbiota varies depending on the residence area and race ³⁸ , ³⁹ , and it is possible that fermented foods, including fermented soybean foods, also affect the gut microbiota and microbe‐associated metabolites ⁴⁰ , including short‐chain fatty acids (SCFAs) and bile acids. It has been reported that SCFAs had a protective effect on diabetes by increasing energy expenditure, insulin sensitivity, and insulin secretion via GPR41and GPR43 ⁴¹ and that secondary bile acids act protectively against diabetes by acting as endogenous ligands for the nuclear receptors FXR and TGR5, a member of G‐protein‐coupled receptor ⁴² , ⁴³ . Although the effects of fermented soybean foods on bile acids have not yet been clarified, soy protein intake has been reported to regulate bile acid metabolism ⁴⁴ .

The effects of each fermented soy food on gut microbiota are summarized in Table 1.

Table 1.

Summary of the effect of fermented soy foods on gut microbiota and diabetes

Fermented soy foods	Gut microbiota	Anti‐diabetic
Miso	↑: phylum Bacteroidetes, genera Bacteroides and Lactobacillus, family Prevotellaceae NK3B31 and genus Desulfovibrio in rat. Families Prevotellaceae, Christensenellaceae, Dehalobacterium, Desulfitibacter; family Deferribacteraceae, order Deferribacterales, class Deferribacteres; and family Gemmatimonadaceae, order Gemmatimonadetes, and class Gemmatimonadales in mouse ↓: phylum Firmicutes, family Peptostreptococcaceae, genera Bifidobacterium and Turicibacter in rat. Family Microbacteriaceae, order Micrococcales, class Actinobacteria, and family Lactobacillaceae in mouse 45 , 46 , 47 , 48	Having antioxidant effect 63 , 64 Having the effect of decreasing of insulin resistance 48
Natto	↑: genera Bifidobacterium, Blautia, and Bacilli in human ↓: phylum Actinobacteria and genera Coriobacteriaceae_UCG‐002, Bacteroides, and Lactococcus in mice; class Clostridia and family Enterobacteriaceae in human 49 , 50 , 51	Having antioxidant effect 72 and anti‐inflammatory effect 74 . Inhabitation of glucose uptake by human intestinal cells 75 and dipeptidyl peptidase IV inhibitory activity 76
Cheonggukjang	↑: genera Coprococcus, Bifidobacterium, and Ruminococcus in human; orders Bacillales, Lactobacillales, and Verrucomicrobiales (Akkermansia muciniphila) in rat ↓: genera Sutterella, Escherichia/Shigella, and Collinsella in human; order Enterobacterales in rat 52 , 53	Having protective effect against apoptosis, inflammation, and oxidative stress 23 . Having positive effects of glucose‐induced insulin secretion in β‐cells and release of glucagon‐like peptide‐1 78 , 79 , 80
Doenjang	↑: phylum Bacteroidetes in mice; genera Odoribacter, Akkermansia, and Lactobacillus in rat ↓: phylum Firmicutes in mice; families Ruminococcaceae and Lachnospiraceae in rat 54 , 55	Having protective effect against oxidative stress 25 , 92 and insulin resistance 54 , 94 , 95 . Having α‐glucosidase inhibitory activity 91
Kochujang	No evidence	Having antioxidant, fibrinolytic, angiotensin‐I‐converting enzyme inhibitory, and adipogenesis inhibitory activities 26 , 91 . Having suppressing effect on lipid accumulation in 3T‐3L1 cell 96 . Suppressing glucose production and triacylglycerol accumulation and increasing glycogen accumulation in hepatocytes 97
Douchi	↑: genera Alistipes, Lactobacillus, Faecalibaculum, Akkermansia, and Bifidobacterium in mice ↓: the phylum Firmicutes/Bacteroidetes ratio, phylum Firmicutes, genera Enterococcus and Oscillibacter, and family Deferribacteraceae in mice 56	Having antioxidant effect 102 , 103 , 104 . Having α‐glucosidase inhibitory activity 106 , 107 , 108 , 109 , 110 , 111 . Having the ability to improve glucose homeostasis in mouse 56
Fermented soy milk	↑: genus Bifidobacterium, Collinsella, and Prevotella in human ↓: unclassified genera of the families Ruminococcaceae and Lachonospiraceae in human 57 , 58	Having antioxidant effect 29 , 112 , 113 and anti‐inflammatory effect 29 . Having the ability of modulating GLUT4 expression in muscles 114
Tempeh	↑: phylum Actinobacteria in Zebrafish; Bacteroidetes, Firmicutes, Clostridium leptum in rat; Bacteroides fragilis, Bifidobacterium, Lactobacillus, Escherichia coli, Enterococcus, and Akkermansia in human ↓: phylum Proteobacteria in Zebrafish 59 , 60 , 61 , 62	Having antioxidant effect 119 , 120 , 121 , 122
Kinema	No evidence	Having antioxidant effect 124 , 125 , 126 , 127

Miso

Pyroglutamyl leucine, isolated from miso, has been shown to decrease the abundance of phylum Firmicutes and to increase the abundance of phylum Bacteroidetes ⁴⁵ . Intake of Zygosaccharomyces sapae (strain I‐6), a probiotic yeast isolated from miso, changed the gut microbiota, such as increasing the abundance of genera Bacteroides and Lactobacillus and decreasing the abundance of family Peptostreptococcaceae and genera Bifidobacterium and Turicibacter, which activated the adenosine 5′‐monophosphate‐activated protein kinase pathway, thereby increasing the peroxisome proliferator‐activated receptor (PPAR)‐γ co‐activator‐1α and carnitine palmitoyltransferase 1α protein expression ⁴⁶ . Furthermore, miso intake increased the abundance of Prevotellaceae NK3B31 and Desulfovibrio and decreased the expression of interleukin (IL)‐1β ⁴⁷ .

Miso intake increases the abundance of the families Prevotellaceae, Christensenellaceae, Dehalobacterium, Desulfitibacter; family Deferribacteraceae, order Deferribacterales, class Deferribacteres; and family Gemmatimonadaceae, order Gemmatimonadetes, and class Gemmatimonadales and decreased the abundance of the family Microbacteriaceae, order Micrococcales, class Actinobacteria, and family Lactobacillaceae in a mouse model, which leads to increased SCFAs ⁴⁸ .

Natto

Natto decreased the abundance of phylum Actinobacteria and genera Coriobacteriaceae_UCG‐002, Bacteroides, and Lactococcus ⁴⁹ . Furthermore, natto supplementation increased the abundance of genera Bifidobacterium and Blautia ⁵⁰ . The consumption of natto led to an increase in stool Bacilli and Bifidobacteria and a decrease in stool Clostridia and Enterobacteriaceae ⁵¹ .

Cheonggukjang

Cheonggukjang increased the abundance of genera Coprococcus, Bifidobacterium, and Ruminococcus and decreased the abundance of genera Sutterella, Escherichia/Shigella, and Collinsella ⁵² . Furthermore, cheonggukjang increased the abundance of orders Bacillales, Lactobacillales, and Verrucomicrobiales (Akkermansia muciniphila) and decreased the abundance of order Enterobacterales, which led to an increase in the production of SCFAs and a decrease in the production of proinflammatory cytokines ⁵³ .

Doenjang

Doenjang decreased the abundance of phylum Firmicutes and increased the abundance of phylum Bacteroidetes. In addition, it decreased the abundance of families Ruminococcaceae and Lachnospiraceae and increased the abundance of genera Odoribacter, Akkermansia, and Lactobacillus, which led to an increase of IL‐10, PPAR‐γ, and carnitine palmitoyltransferase‐1 expression and a decrease of lipopolysaccharide concentrations ⁵⁴ , ⁵⁵ .

Douchi

One study investigated the effect of douchi, a Chinese fermented black bean, on gut microbiota. Supplementation of peptides VY and SFLLR, which are identified from douchi, decreased the Firmicutes/Bacteroidetes ratio (which was increased in those consuming the high‐fat diet); increased the abundance of family Deferribacteraceae, genera Alistipes, Lactobacillus, Faecalibaculum, Akkermansia, and Bifidobacterium; and decreased the abundance of phylum Firmicutes, genera Enterococcus, and Oscillibacter which led to an increase in the levels of SCFAs and IL‐10 ⁵⁶ .

Fermented soy milk

Fermented soy milk increased the abundance of the genera Bifidobacterium, Collinsella, and Prevotella and decreased the abundance of unclassified genera of the families Ruminococcaceae and Lachonospiraceae ⁵⁷ , ⁵⁸ , which led to an increase in SCFA production.

Tempeh

Tempeh supplementation decreased the abundance of phylum Proteobacteria and increased the abundance of phylum Actinobacteria in Zebrafish ⁵⁹ . Tempeh increased the abundance of Bacteroidetes, Firmicutes, Clostridium leptum, and Bacteroides fragilis in a rat model ⁶⁰ . Tempeh supplementation also increased the abundance of Bifidobacterium, Lactobacillus, Escherichia coli, Enterococcus, and Akkermansia in humans ⁶¹ , ⁶² .

POTENTIAL BENEFICIAL EFFECT OF FERMENTED SOYBEAN FOODS ON DIABETES

A summary of the effects of each fermented soybean food on diabetes is shown in Table 1.

Miso

In vitro

Miso exerts an antioxidant effect by improving the 1,1‐diphenyl‐2‐picryl‐hydrazyl (DPPH) radical scavenging ability ⁶³ , ⁶⁴ .

Animal study

A study using an animal model reported that miso consumption suppresses fatty liver and visceral fatty obesity induced by a high‐fat diet ⁶⁵ . Moreover, miso consumption suppresses insulin resistance ⁴⁸ .

Human study

Cross‐sectional studies have reported that miso consumption reduces insulin resistance in individuals without diabetes ⁶⁶ , ⁶⁷ as well as the incidence of gestational diabetes ⁶⁸ . Furthermore, cross‐sectional studies in patients with type 2 diabetes revealed better glycemic control and significantly lower relative muscle mass loss in miso soup consumers ⁶⁹ , ⁷⁰ .

Natto

In vitro

It has been shown that natto inhibits glucose uptake by human intestinal cells ⁷¹ and that natto inhibits dipeptidyl peptidase IV ²¹ .

Animal study

Animal study revealed that natto exerts antioxidant effects ⁷² and anti‐inflammatory effects by increasing IL‐10 levels ⁷³ . A study using an animal model reported that natto consumption suppresses fatty liver ⁷⁴ .

Human study

Moreover, cross‐sectional and randomized crossover studies have shown that natto intake is associated with the suppression of postprandial blood glucose and insulin resistance ⁷⁵ , ⁷⁶ , ⁷⁷ .

Cheonggukjang

Cheonggukjang has been reported to have protective effects against apoptosis, inflammation through nuclear factor‐kappa B activation, and oxidative stress through the formation of superoxide anion by removal of the tumor‐promoting factor hydrogen peroxide ²³ .

In vitro

Cheonggukjang extracts showed positive effects on glucose‐induced insulin secretion in β‐cells ⁷⁸ , elevating the release of glucagon‐like peptide‐1 from L‐cells to increase serum glucagon‐like peptide‐1 concentrations ⁷⁹ , ⁸⁰ , and inhibiting lipid accumulation in 3 T3‐L1 cells ⁸¹ , ⁸² .

Animal study

Several studies using animal models have shown that cheonggukjang intake improves blood glucose levels and suppresses body weight gain ⁷⁹ , ⁸⁰ , ⁸³ , ⁸⁴ , ⁸⁵ . Furthermore, cheonggukjang intake improved blood lipid levels in animal models ⁸⁶ , ⁸⁷ .

Human study

Cheonggukjang intake improved fasting blood glucose levels in individuals with impaired fasting glucose levels ⁸⁸ . Furthermore, several studies on individuals with overweight or obesity showed that compared with controls, plasma apoB levels and body fat decreased in participants who consumed cheonggukjang ⁸⁹ , ⁹⁰ .

Doenjang

In vitro

Doenjang inhibited α‐glucosidase in an in vitro study ⁹¹ . Doenjang has been reported to have protective mechanisms against oxidative stress, including the inhibition of intracellular reactive oxygen species production and glutamate‐induced cytotoxicity ⁹² , ⁹³ .

Animal study

The increase in PPAR‐γ through changes in the gut microbiota may be associated with reduced insulin resistance ⁵⁴ , ⁹³ . Several animal model studies have shown that doenjang intake improves insulin resistance and visceral fat ⁹⁴ , ⁹⁵ .

Kochujang

In vitro

It has been clarified that kochujang has antioxidant, fibrinolytic, and angiotensin‐I‐converting enzyme inhibitory activities ²⁶ . Kochujang showed adipogenesis inhibitory activity in vitro and reduced ⁹¹ lipid accumulation through suppression of lipogenesis by downregulating sterol regulatory element‐binding protein‐1c and stimulation of lipolysis by increasing hormone‐sensitive lipase ⁹⁶ .

Animal study

Animal studies have shown that kochujang improves insulin resistance by suppressing hepatic glucose production and triacylglycerol accumulation and increasing glycogen accumulation ⁹⁷ .

Human study

Several randomized controlled clinical trials involving individuals with obesity have shown that kochujang intake reduces blood lipid levels, body weight, and visceral fat ⁹⁸ , ⁹⁹ , ¹⁰⁰ , ¹⁰¹ .

‘Jang’, such as cheonggukjang, doenjang, and kochujang, intake was associated with a low risk of metabolic syndrome in a cohort study ¹⁰² .

Douchi

In vitro

A previous study revealed that douchi has an antioxidant effect via DPPH radical scavenging activity and an increase in superoxide dismutase, glutathione peroxidase, and catalase, which are known antioxidant enzymes ¹⁰³ , ¹⁰⁴ . Douchi also has antioxidant capacity, as measured by protease and β‐glucosidase activities ¹⁰⁵ .

Animal and human study

Several previous in vivo animal and human studies have reported that douchi has α‐glucosidase inhibitory activity ¹⁰⁶ , ¹⁰⁷ , ¹⁰⁸ , ¹⁰⁹ , ¹¹⁰ , ¹¹¹ . Moreover, a recent study showed that the peptides VY and SFLLR improve glucose homeostasis by activating glycogen synthase and inhibiting phosphoenolpyruvate carboxykinase and glucose 6‐phosphatase ⁵⁶ .

Fermented soy milk

In vitro

Fermented soy milk exerts antioxidant effects by increasing nitric oxide secretion and other antioxidant enzymes and improving DPPH radical scavenging ability ²⁹ , ¹¹² , ¹¹³ . Fermented soy milk has also been reported to exert anti‐inflammatory effects ²⁹ . Fermented soy milk can reduce blood glucose levels by modulating GLUT4 expression in muscles ¹¹⁴ .

Animal study

Several studies with animal models have shown that serum lipid levels were decreased by fermented soy milk through inhibition of sterol regulatory element‐binding protein‐dependent cholesterol and triglycerides synthesis in the liver and enhancement of adiponectin signaling and PPAR‐α, fatty acid oxidation, and reverse cholesterol transport in adipose tissues ¹¹⁵ , ¹¹⁶ , ¹¹⁷ , ¹¹⁸ .

Tempeh

In vitro

Tempeh has an antioxidant effect by improving the DPPH radical scavenging ability ¹¹⁹ , ¹²⁰ .

Animal study

Several studies using animal models have reported that tempeh improves blood glucose and lipid levels by altering the gut microbiota, leading to the inhibition of cholesterol synthesis, promotion of lipolysis, increased antioxidative capacity, and lowered reactive oxygen species levels ¹²¹ , ¹²² .

Human study

A prospective open‐label trial showed that tempeh consumption improves glycemic control and triglyceride levels ¹²³ .

Kinema

In vitro and animal study

It has been reported that kinema exerts antioxidant effects by improving DPPH radical scavenging ability ¹²⁴ , ¹²⁵ , ¹²⁶ , ¹²⁷ . Thus, although no studies have shown an association between kinema and diabetes, kinema intake may affect diabetes.

CONCLUSION

In this study, we summarize the effects of fermented soybean foods on diabetes. Diet is associated with type 2 diabetes through changes in the gut microbiota.

Fermented soybean foods contain a variety of health‐beneficial components, and their continuous intake improves dysbiosis, which in turn promotes the production of gut microbiota‐related metabolites, including SCFAs and bile acids (Figure 1). Dietary habits may contribute to differences in gut microbiota by region of residence and race; thus, the consumption of fermented soybean foods specific to each region and race may more efficiently modify dysbiosis and alter gut microbiota‐related metabolites.

Figure 1.

Mechanisms by which fermented soy foods affect diabetes.

There are still many unknowns regarding fermentation and fermented foods, including fermented soybean foods. In recent years, research on various fermented foods has increased worldwide, and new findings are expected to emerge in the future. We hope that this article will help readers to understand fermented foods and will be of some help in daily medical practice.

AUTHOR CONTRIBUTIONS

Yoshitaka Hashimoto: Conceptualization; Data curation; Investigation; Methodology; Project administration; Resources; Visualization; and Roles/Writing – original draft. Masahide Hamaguchi: Data curation; Supervision; Validation; Visualization; and Writing – review & editing. Michiaki Fukui: Funding acquisition; Project administration; Supervision; and Writing – review & editing. All authors have checked the final version and agree to be responsible for the work to ensure that any questions related to the accuracy or completeness of any work are appropriately investigated and resolved.

FUNDING

None.

DISCLOSURE

Dr Hashimoto reports personal fees from Novo Nordisk Pharma Ltd, Sanofi K.K., Mitsubishi Tanabe Pharma Corp., Ono Pharma Co. Ltd, Nippon Boehringer Ingelheim Co. Ltd, Kowa Pharma Co. Ltd, and Sumitomo Dainippon Pharma Co. Ltd. Dr Hamaguchi received grants from Daiichi Sankyo Co. Ltd, Nippon Boehringer Ingelheim Co. Ltd, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corp., Novo Nordisk Pharma Ltd, Sanofi K.K., Takeda Pharma Co. Ltd, Sumitomo Dainippon Pharma Co. Ltd, Asahi Kasei Pharma, Kyowa Kirin Co. Ltd, and Eli Lilly Japan K.K. outside the submitted work. Prof. Fukui received grants from Taisho Pharma Co., Ltd, Mitsubishi Tanabe Pharma Corp, Novo Nordisk Pharma Ltd, Ono Pharma Co. Ltd, Kowa Pharma Co. Ltd, Sanofi K.K., Nippon Boehringer Ingelheim Co. Ltd, Daiichi Sankyo Co. Ltd, Kissei Pharma Co. Ltd, MSD K.K., Kyowa Kirin Co., Ltd, Sumitomo Dainippon Pharma Co. Ltd, Eli Lilly Japan K.K., Tejin Pharma Ltd, Takeda Pharma Co. Ltd, Nippon Chemiphar Co. Ltd, Astellas Pharma Inc., Abbott Japan Co. Ltd, Sanwa Kagagu Kenkyusho Co. Ltd, Johnson & Johnson k.k. Medical Co., and Terumo Corp., and received honoraria from AstraZeneca K.K., Taisho Pharma Co. Ltd, Ono Pharma Co. Ltd, Novo Nordisk Pharma Ltd, Sanofi K.K., Teijin Pharma Ltd, Takeda Pharma Co. Ltd, Astellas Pharma Inc., MSD K.K., Mitsubishi Tanabe Pharma Corp., Eli Lilly Japan K.K., Kissei Pharma Co. Ltd, Sumitomo Dainippon Pharma Co. Ltd, Daiichi Sankyo Co. Ltd, Mochida Pharma Co. Ltd, Kowa Pharma Co. Ltd, Arkray Inc., Abbott Japan Co. Ltd, Sanwa Kagaku Kenkyusho Co. Ltd, Kyowa Kirin Co. Ltd, Nippon Boehringer Ingelheim Co. Ltd, Medtronic Japan Co. Ltd, Bayer Yakuhin, Ltd, and Nipro Corp. outside the submitted work. The other authors declare no conflict of interest.

Approval of the research protocol: N/A.

Informed consent: N/A.

Registry and the registration no. of the study/trial: N/A.

Animal studies: N/A.