In the last few years, many studies have highlighted the relationship between diet and health status with the aim of improving both disease prevention and life expectancy. The human gastrointestinal tract is home to more than a trillion live bacteria from about four hundred species. The average adult body contains about twenty more times more bacteria than it does somatic cells.³  The human gut microbiota has a significant effect on many aspects of human physiology such as metabolism, nutrient absorption, and immune function. Imbalance of the microbiota has been implicated in many disorders including inflammatory bowel disease, obesity, asthma, psychiatric illnesses, and cancers. 

Warning to Those Doing Gut Microbe Testing

There are more gaps in our knowledge than we think and the potential risks of overconfidence in current microbiome-based functional medicine practices. As we explore this microbe and its implications, we’re posed with a potentially uncomfortable parallel for some – could our current certainty about microbiome testing and treatments someday be viewed with the same absurdity we view the medical practices of centuries past?

Cancer Prevention and Treatment Support

Research demonstrates that probiotic-rich foods play a protective role against cancer development in animal models. When applied clinically, these foods can:

• Reduce postoperative inflammation in cancer patients¹  
• Enhance the effectiveness of immune checkpoint inhibitors²  
• Improve outcomes from chemotherapy³   and radiation treatments⁴
• Decrease post-surgical complications⁵ 

Benefits of Traditional Fermented Foods

Traditional fermented foods constitute an important part of human diets globally and contain exceptional microbial biodiversity. This diversity creates a unique source of metabolites with potential health benefits. Recent studies have identified multiple positive health effects from fermented foods, including:

• Cardiovascular protective effects⁶  
• Antiproliferative activity that may aid in cancer prevention⁷ 

Lactic acid fermentation plays an important role in preserving fresh vegetables, fruits, and other food items for feeding humanity in developing countries. Lactic acid fermentation increases shelf life of fruits and vegetables and also enhances several beneficial properties, including nutritive value and flavors, and reduces toxicity. Fermented fruits and vegetables can be used as a potential source of probiotics as they harbor several lactic acid bacteria such as Lactobacillus plantarum, L. pentosus, L. brevis, L. acidophilus, L. fermentum, Leuconostoc fallax, and L. mesenteroides. As a whole, the traditionally fermented fruits and vegetables not only serve as food supplements but also contribute towards health benefits.⁸   Live cultures are found in not only yogurt and a yogurt-like drink called kefir, but also in Korean pickled vegetables called kimchi, sauerkraut, and in some pickles.

The association of probiotics with well-being has a long history. More than a century has passed since Tissier observed that gut microbiota from healthy breast-fed infants were dominated by rods with a bifid shape (bifidobacteria) which were absent from formula fed infants suffering from diarrhea, establishing the concept that they played a role in maintaining health.

Certain yogurts and other cultured dairy products contain such helpful bacteria, particularly specific strains of Bifidobacteria and Lactobacilli. Not all bacteria present in fermented milk products or yogurt have a probiotic effect. For this reason, in order to consider a Lactobacillus or Bifidobacterium a probiotic, the specific strains selected must exert a clinically established health benefit.⁴  

Recent studies have suggested that the intestinal microbiome plays an important role in modulating risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, and cancer. Recent research has illustrated a pivotal role of the gut microbiota in almost every cancer. In some cases, certain gut bacterial species are oncogenic by themselves; examples include Helicobacter pylori in gastric cancer, and Salmonella Typhi in gallbladder cancer.^9,10   These bacteria can stimulate a local chronic inflammatory state that promotes carcinogenesis via the induction of proinflammatory toxins, increased production of reactive oxygen species, alterations in signaling pathways, or prevention of anti-tumor immune functions.¹¹  

Diet plays a significant role in shaping the microbiome, with experiments showing that dietary alterations can induce large, temporary microbial shifts within 24 hours. Given this association, there may be significant therapeutic utility in altering microbial composition through diet. This review systematically evaluates current data regarding the effects of several common dietary components on intestinal microbiota. We show that consumption of particular types of food produces predictable shifts in existing host bacterial genera. Furthermore, the identity of these bacteria affects host immune and metabolic parameters, with broad implications for human health. Familiarity with these associations will be of tremendous use to the practitioner as well as the patient.

These food-derived bacteria and their metabolites can interact with the intestinal microbiome and with the host itself like members of an orchestra playing a health symphony for the intestine and the organisms in general.¹²   

Impact of diet on the gut microbiome and human health

Impact of dietary protein on intestinal microbiota and health outcomes. SCFA’s short chain fatty acids, TMAO trimethylamine N-oxide, Tregs T regulatory cells, CVD cardiovascular disease; IBD inflammatory bowel disease.

Impact of dietary fats on intestinal microbiota and host metabolism. TLR toll-like receptor, WAT white adipose tissue, LDL low-density lipoprotein.

The impact of diet on the microbiota and systemic immunity. Diet has an impact on the host microbiota with the western diet being linked with dysbiosis. Conversely, diets that are high in fiber have been associated with bacterial diversity in the microbiota, which is postulated to support appropriate T-cell differentiation. These patients are likely to experience enhanced responses to CIT.¹⁴  

Throughout history, fermenting foods helped prolong the freshness of grains, vegetables and milk that were available to them during different seasons.

Several years ago (02-06-2013) I wrote a blog entitled “Have You Had Your Fermented Foods Today?” (https://www.donnieyance.com/have-you-had-your-fermented-foods-today/) I would suggest reading this as well. I would also suggest you read my blog on Sun chokes entitled “Sunchokes: A Humble Food With Many Health Benefits” (https://www.donnieyance.com/sunchokes-a-humble-food-with-many-health-benefits/), which are a great prebiotic.  Prebiotics are just as essential to a healthy microbiome. They work symbiotically with probiotic nutrients to help form healthy gut bacteria.

Fermented foods support our health in the following ways: 

• Boost immunity – associated with aiding in cancer therapies, specifically immunotherapy,
• Improve digestion and GUT health,
• Improve cognition,
• Help treat irritable bowel disease¹⁴   and other digestive conditions,
• Provide us with an array of highly bioavailable nutrients, including secondary nutrients, which are vitally important to our health and disease resistance,
• Help with allergies and autoimmune disease,
• Help rid the body of harmful microbes,
• Help manage proper weight, and
• Help with hormonal balance.

Basic characteristics of selection of a probiotic strains.¹⁶  

Scheme of lactic acid bacteria bioactive compounds and health-related effects.¹⁷  

Gut microbiome modulates tumor response to checkpoint blockade immunotherapy.¹⁸  

Lactobacillus plantarum has many health promoting effects including autism,¹⁹  can be found in fermented foods and beverages such as the following:

• Brined olives
• Kimchi
• Pickles
• Raw sourdough (note, L. plantarum mostly can’t survive the high temperatures of baking)
• Sauerkraut
• Some cheeses²⁰  

Akkermansia muciniphila 

Beneficial bacteria such as Bifidobacterium and lactic acid-producing bacteria have been shown to improve the intestinal environment, and yield a good effect on metabolism, immunity and nerve response. In this review, in addition to these beneficial bacteria, we introduced Akkermansia muciniphila as a next-generation beneficial microbe. Several reports indicate that Akkermansia muciniphila affects glucose metabolism, lipid metabolism, and intestinal immunity, and that certain food ingredients such as polyphenols may increase the abundance of Akkermansia muciniphila in the gut.

Akkermansia muciniphila is a gram-negative, anaerobic (thrives in low-oxygen environments) bacteria that lives in the mucus layer of the colon. It is one of the most abundant bacteria in the gut microbiome, constituting up to 5% of the total bacteria in the gut in healthy adults.

• Akkermansia and gut mucus: In the mucus layer, it feasts on the glycoproteins (i.e. proteins decorated with sugar molecules) that make up this mucus, and creates the short chain fatty acids acetate and propionate as byproducts.
• Relation with leaky gut: Mucus breakdown by Akkermansia stimulates the differentiation of stem cells into mucus-producing cells. Therefore, the net effect of Akkermansia is improvement in rates of mucus production and the integrity of the mucus layer.

Akkermansia muciniphila: A Potential Booster to Improve the Effectiveness of Cancer Immunotherapy

The gut microbiome Akkermansia muciniphila (A. muciniphila) can significantly inhibit carcinogenesis and improve anti-tumor effects, thus increasing the effectiveness of cancer immunotherapy and decreasing the likelihood of side effects. A. muciniphila mediates effects on host metabolism and can influence the efficacy of anti-PD-1-based immunotherapy against cancer. The mechanisms for these effects remain poorly understood, but both appear to be immune-mediated and correlate with type 1 immunity. In particular, responses to anti-PD-1-based immunotherapy in humans correlated with interferon gamma production by peripheral T cells when incubated with A. muciniphila antigens in vitro. The potential clinical applications of A. muciniphila on cancer immunotherapy are also proposed, which have great prospects for anti-tumor therapy.^22,23   

Akkermansia muciniphila Improves Gastric Cancer Treatment by Modulating the Immune Microenvironment

Gut microbiota is pivotal in tumor occurrence and development, and there is a close relationship between Akkermansia muciniphila and cancer immunotherapy. 

Methods: The effects of Akkermansia muciniphila  and its outer membrane proteins on gastric cancer (GC) were evaluated in vitro and in vivo using cell counting kit-8 assay, flow cytometry, western blotting, ELISA, immunohistochemistry, and immunofluorescence. 

Results: Akkermansia muciniphila outer membrane protein facilitated apoptosis of GC cells and exerted an immunostimulatory effect (by promoting M1 polarization of macrophages, enhancing expression of cytotoxic T-lymphocyte-related cytokines and suppressing that of Treg-related cytokines). 

Additionally, Akkermansia muciniphila  and its formulation could inhibit tumor growth of GC and enhance the infiltration of immune cells in tumor tissues.²⁴  

Akkermansia populations are also supported by key prebiotics. Prebiotics are molecules that pass through our digestive systems intact and reach to the colon where they can support the growth of beneficial microbes. The prebiotics that promote Akkermansia growth include polyphenols and human milk oligosaccharides (HMOs).²⁵  

Polyphenols

Polyphenols are antioxidant molecules found in a variety of foods, and can often be identified by their vibrant colors. For example, the dark purple-blue pigments found in blueberries, blackberries, cranberries, and red cabbage are a group of polyphenols known as anthocyanins. Polyphenols have the ability to neutralize free radicals and, in doing so, protect against oxidative stress and inflammation.

Polyphenols derived from grapes act to increase the abundance of Akkermansia in the intestinal tract; as a result, they have been shown to enhance intestinal barrier function and incretin secretion from intestinal endocrine cells.^26,27  Polyphenols derived from cranberries have also been reported to increase the abundance of Akkermansia, as well as help suppress obesity, insulin resistance, and intestinal inflammation.²⁸  

In addition to their direct anti-inflammatory effects, polyphenols can also feed Akkermansia and another important group of bacteria in the gut known as Bifidobacteria. Therefore, polyphenol consumption can support the colonization of the gut by these two key groups of bacteria.

• Grape polyphenols: Research has demonstrated that the consumption of grape polyphenols increases the levels of Akkermansia present in the gut. Moreover, this increase in Akkermansia was associated with enhanced intestinal barrier integrity and elevated secretion of hormones known as incretins from small intestinal cells. Incretins play an important role in the maintenance of healthy weight, glucose levels, and satiety.²⁹  
• Cranberry polyphenols: Cranberry polyphenols have also been shown to support Akkermansia populations and exert protective effects against obesity, insulin resistance, and inflammation within the intestines.^30,31  
• Apple peels: Similarly, animal models suggest that the polyphenols present in red apple peels, known as procyanidins, partially protect against the weight gain, inflammation, and liver dysfunction characteristic of a high fat, high sugar diet. These benefits were attributed to improvements in the microbiome, one of which was heightened levels of Akkermansia.

Fructooligosaccharides (FOS)

Fructooligosaccharides (FOS) are chains of fructose molecules linked together that serve as a food source for bacteria in the colon. FOS are found in foods such as onion, asparagus, banana, and artichoke.

Although there have not yet been studies looking at the effects of FOS consumption on Akkermansia populations in humans, multiple animal studies have shown that FOS can increase levels of Akkermansia especially in models of obesity and diabetes. Moreover, FOS consumption was linked to reduced fat mass, decreased gut permeability, and enhanced blood sugar control in these models. These benefits were attributed to the enhancements in Akkermansia levels in response to FOS feeding.

Berberine

Berberine is a plant alkaloid that stimulates pathways in the body associated with fasting, making it a fasting mimetic. It has proven benefits on metabolic health, including lipid-lowering and anti-obesity effects, and improved glucose control.

Studies conducted in rodent models suggest that berberine is extremely effective at bolstering levels of Akkermansia in the gut in a dose-dependent manner, and that this effect is likely partially responsible for its health benefits.³²  

Although these results have not yet been recapitulated in humans, the metabolic benefits of berberine are consistent across rodents and humans, which suggests that the effects on Akkermansia may also be conserved.

Probiotics and Postbiotics

In addition to dietary and lifestyle strategies, research efforts are also geared towards determining whether Akkermansia probiotics could confer benefits to human health. Although there is a dearth of research examining the effects of Akkermansia probiotics in humans, several studies have been conducted in animal models of diet-induced obesity.

Rodent models of diet-induced obesity (DIO) fed a high fat, high sugar diet mimicking a Standard American Diet exhibit suppressed populations of Akkermansia and develop similar conditions as human with diet-induced obesity including systemic inflammation, arterial plaque, breakdown of the gut mucus layer, and insulin resistance.

Upon four to eight weeks of treatment with an Akkermansia probiotic, DIO mice exhibit restored levels of Akkermansia as measured in fecal samples, with no other changes to the microbiome composition. Additionally, these animals showed reduced levels of inflammation, shrinking of plaques, restored gut mucus layer thickness, reduced body weight, and improved insulin sensitivity.

However, these benefits were only seen with the higher dose probiotic not the lower dose suggesting that dosing may be an important consideration when using Akkermansia probiotics in the setting of obesity and metabolic dysfunction in humans.

Green Tea Encourages Growth of Akkermansia muciniphila

Trillions of microorganisms reside in the host’s gut. Since diverse activities of gut microbiota affect the host’s health status, maintenance of gut microbiota is important for maintaining human health. Green tea (GT) has multiple beneficial effects on energy metabolism with antiobesity, antidiabetic, and hypolipidemic properties. As GT contains a large amount of bioactive ingredients (e.g., catechins), which can be metabolized by microorganisms, it would be feasible that consumption of GT may cause compositional changes in gut microbiota, and that the changes in gut microbiota would be associated with the beneficial effects of GT. In this study, we demonstrated that consumption of GT extract relieves high-fat diet-induced metabolic abnormalities. Interestingly, GT administration significantly encouraged the growth of Akkermansia muciniphila (Akkermansia), a beneficial microorganism to relieve obesity and related metabolic disorders. Finally, we found that epigallocatechin gallate is the component of GT that stimulates the growth of Akkermansia. According to these data, we propose that GT could be a prebiotic agent for Akkermansia to treat metabolic syndromes.³³  

Flaxseed Lignans Combined with PD-1/PD-L1 Inhibitor Reduces Breast Cancer Growth by Modulating Gut Microbiome and Immunity

Few breast cancer (BC) patients respond to PD-1/PD-L1 inhibitors (PDi). We investigated whether flaxseed lignans (FL) could enhance PDi efficacy in BC treatment. This study analyzed enterolactone (ENL), the gut bacterial product of FL, and identified CD38 as its target gene. We assessed the ENL/CD38 axis effects on BC cells through various assays. Immune environment changes were evaluated using immunohistochemistry and CyTOF, while gut microbiota changes were assessed by 16S rDNA sequencing.

FL converted to ENL by gut bacteria inhibited BC progression by downregulating CD38, which is linked to immunosuppression and PDi resistance. FL treatment increased beneficial immune cells and reduced immunosuppressive cells. The FL-PDi combination significantly increased Akkermansia bacteria, which enhanced PDi response in antibiotic-treated mice.

The FL/ENL/CD38 pathway inhibits BC progression. FL enhances PDi effectiveness by modifying gut bacteria and improving immune response.³⁴ 

Bifidobacteria Cross-feeds Akkermansia

In other animal studies, researchers supplemented obese rodents with a probiotic containing  Bifidobacterium animalis (*subspecies lactis) to see if bolstering the levels of this species in the gut could indirectly boost levels of Akkermansia. 

Indeed, treatment of the animals with this species for 14 weeks resulted in a dramatic increase in the fecal content of A. muciniphila. The group treated with this probiotic also gained less weight than control animals also fed the high fat, high sugar diet.³⁵  

The mechanism by which B. animalis promotes the growth of A. muciniphila is still unknown, however the researchers postulate that it may be due to enhanced butyrate production facilitated by B. animalis, as butyrate stimulates mucus production in the gut.

Below is a list of some of the best fermented foods to include in your weekly diet:

Kefir and Yogurt

Kefir is a fermented milk product (made from cow, goat or sheep’s milk) that tastes like a drinkable yogurt. Kefir has been consumed for well over 3,000 years. The term kefir was started in Russia and Turkey and means “feeling good.”

Kefir contains a specific and complex mixture of bacteria and yeasts that live in a symbiotic association. The nutritional composition of kefir varies according to the milk composition, the microbiological composition of the grains used, the time/temperature of fermentation and storage conditions. Kefir originates from the Caucasus and Tibet. Regular consumption of kefir has been associated with improved digestion and tolerance to lactose, antibacterial effect, hypocholesterolaemic effect, control of plasma glucose, anti-hypertensive effect, anti-inflammatory effect, antioxidant activity, anti-carcinogenic activity, anti-allergenic activity and healing effects.^36,37   

Kefir production faces more than one challenge, owing to the unique and diverse microflora of kefir grain, milk type, incubation time and storage conditions. 

Kefir provides high levels of vitamin B12, calcium, magnesium, vitamin K2, biotin, folate, enzymes and probiotics.

Biological Properties, Nutritional Value, and Macro- and Micronutrient Composition of Kefir³⁸ 

Lactobacillus gasseri

Lactobacillus (L) gasseri is found in many fermented foods but in minimal quantities. It can be found in puba, or carimã, a Brazilian food made with fermented cassava, and in kefir. Breast milk also contains L. gasseri in important quantities.

I like to switch between kefir and yogurt, as well as between the various milk-based products, which include goat, cow, sheep, and coconut.

L. gasseri is a unique product that offers many health benefits, including weight loss,^39-41   lipid control,⁴²   vaginal and bladder health,⁴³  premenstrual related issues, such as cramping,⁴⁴   menopausal symptom relief,⁴⁵   inhibition of H pylori,⁴⁶ and immunity, including improving autoimmune conditions, and allergies.⁴⁷  

Yogurt and kefir are unique dairy products because they are highly available and some of the top probiotic foods that many people eat regularly. Probiotic yogurt is now the most consumed fermented dairy product in the United States and many other industrialized nations too.

It’s recommended when buying yogurt to look for three things:

1. It comes from goat or sheep milk if you have trouble digesting cow’s milk.
2. It’s made from the milk of animals that have been grass-fed.
3. It’s organic.

Yogurt Intake Reduces Mortality: Meta-Analysis of Eight Cohort Studies

Methods

We searched PubMed, EMBASE, and Web of Science for studies on yogurt intake and mortality risk through October 2018. Quality assessment used the Newcastle-Ottawa Scale, and results were analyzed using random effects models.

Results

Analysis included 235,676 participants across eight cohort studies, with 14,831 deaths recorded. Key findings:

• Highest vs. lowest yogurt consumption showed no significant reduction in all-cause mortality (HR=0.93; 95% CI: 0.85-1.01)
• Yogurt intake ≥200g/day significantly reduced:
  • All-cause mortality (HR=0.88; 95% CI: 0.80-0.96)
  • Cardiovascular mortality (HR=0.87; 95% CI: 0.77-0.99)
• Dose-response analysis confirmed that 200g/day yogurt intake was inversely associated with mortality

Conclusion

Evidence suggests yogurt consumption can reduce all-cause and cardiovascular mortality. More research needed to confirm protective effects.⁴⁸  

Coconut Kefir

For those who can’t tolerate dairy, coconut kefir is a great alternative. This probiotic-rich drink is made with creamy coconut milk and kefir grains, but unlike regular kefir or yogurt it’s dairy-free and vegan-friendly. Coconut kefir also contains many probiotic, bioactive compounds and as many as 30 strains of good bacteria.⁴⁹  

One specific probiotic bacteria is called Lactobacillus kefiri, and it helps defend against harmful bacteria like salmonella and E. coli. This bacterial strain, along with the various other handfuls, help modulate the immune system and inhibit many predatory bacteria growth.⁵⁰  

Try it in smoothies, in baked goods, with fruit, on its own, etc. Just opt for brands that are low in sugar or unflavored, and consider adding your own stevia, fruit or honey for extra flavor.

Probiotic yogurt modulated the gut microbiota in mice by increasing the abundance of short-chain fatty acid (SCFA)-producing bacteria and SCFA levels (acetic acid, propionic acid, butyric acid, and valeric acid) in the feces. Probiotic yogurt has demonstrated antihypertensive effects in animals.⁵¹   

Raw Cheese

Raw cheeses are made with milk that hasn’t been pasteurized. Goat milk, sheep milk, and A2 cows soft cheeses are particularly high in probiotics, including thermophillus, bifidus, bulgaricus and acidophilus.⁵²  

Reggiano Parmesan cheese

Reggiano Parmesan, which I am somewhat addicted to, has a delicious sharp, nutty, and slightly salty flavor. The health benefits of nutrient dense parmesan cheese include immune system, digestive system, nervous system, and bone health (over 1000 mg. per 100 grams). Reggiano Parmesan a cheese easily digested, for the presence of ready-to-use proteins and lipids, lactose free, rich in calcium, with possible prebiotic and probiotic effect.¹²  

Reggiano Parmesan is a ripened cheese with high nutritional value. Throughout ripening the bacteria contained in Parmigiano Reggiano promote an extensive hydrolysis of cow’s milk proteins resulting in peptides that exhibit positive immunoregulatory activities.

The proteins of Reggiano Parmesan are characterized by a high biological value. In fact, they contain high concentrations of all the essential amino acids. Amino acids such as isoleucine, leucine, lysine, threonine, tryptophan, valine, methionine, phenylalanine, tyrosine, and histidine are present in optimal amounts and in a particularly bioavailable form.  In particular, the high content of lysine in cheese protein is noticeable.¹²   

During the Parmigiano Reggiano ripening process a discrete amount of short-chain fatty 

acids (SCFAs) are synthesized with a considerable production of butyrate. It is important to highlight that Parmigiano Reggiano contains 100% more butyrate than other fermented cheeses.¹³  

The probiotic Lactobacillus rhamnosus (LR) contained in Parmigiano Reggiano plays a crucial role in producing high levels of enzymes responsible for the proteolytic activity, fatty acids metabolism and for the release of butyrate. LR has been very well studied and has been shown in a number of different settings to aid in immunity.  Various health effects are well documented including the prevention and treatment of gastro-intestinal infections and diarrhea, and stimulation of immune responses that promote vaccination or even prevent certain allergic symptoms.¹⁴  There is good evidence for the use of LR in the prevention and treatment of diarrhea, from acute infections or drug related.¹⁵  One study found that LR could be just as helpful as an antibiotic for treating urinary tract infections.¹⁶   

Lactobacillus rhamnosus: An Overview to Explore the Rationale of Its Use in Cancer

Lactobacillus rhamnosus (LR) is one of the most characterized and utilized. In particular, LR is able to reverse intestinal dysbiosis and moderate diarrhea. Moreover, preclinical studies have documented its effects in reducing chronic inflammation associated with cancer development. LR should be considered in patients undergoing specific therapeutic protocols, including chemotherapy and pelvic radiotherapy, in order to reduce the development of severe diarrhea and thus improve the adherence to the therapy and patients’ quality of life.

TJ (tight junction), DC (dendritic cell), LGG (Lactobacillus rhamnosus)

LR may be helpful in those patients undergoing anti-cancer treatments. It protects against tumor onset and invasiveness, lowers the metabolism of oncogenic substrates, increases the production of IgAs, protects against local inflammation, diminishes crypt loss and apoptosis during radiation therapy. Finally, it has shown to be helpful in reducing diarrhea severity and incidence in cancer patients.²⁰   

Parmigiano Reggiano cheese showed that it can have up to 10 million colony forming units of viable lactic acid bacteria per gram of product when you eat it.¹⁷   

By analyzing the Parmigiano Reggiano composition and considering its high content in hydrolysates peptides, the presence of butyrate and other bacterial components, it is easy to hypothesize that this cheese has a high potential to benefiting immune health.

Based on its nutritional characteristics and of its easy digestibility Parmigiano Reggiano cheese is recommended in all feeding age groups.¹⁸   

Sourdough Bread

Sourdough is the oldest form of leavened bread used as early as 2000 BC by the ancient Egyptians. Fermentation helps make nutrients found in the grains more available for absorption and reduces antinutrient content that may make digestion difficult. Sourdough bread is unique, delicious, and loaded with health benefits for our bodies. The starter used to make sourdough bread is a probiotic, but really it is actually prebiotic. As each sourdough starter is unique, with different activities, populations, and interactions of yeast and bacteria due to different ingredients, environment, fermentation time and its carbohydrate fermentation pattern, there is no exact elucidation on the complete make-up of the sourdough microbiome. Some lactic acid bacteria (LAB) strains that are part of the sourdough starter are considered as probiotics which have great potential for improving gastrointestinal health. 

This fermentation process improves digestibility and enhances fiber availability. Many with non-celiac gluten sensitivity tolerate sourdough better because fermentation breaks down gluten proteins. For maximum benefits, traditional long-fermented varieties are essential.

The dynamics and diversity of microbiomes in sourdough are known to give many benefits to bread and mankind. These are not only wholesome nutrients but also distinctive functions and benefits for health.⁵³  Nutritious sourdough whole grain should be a staple for a healthy balanced diet for a variety of reasons. In fact, whole grains contribute valuable nutrients to your diet, and can even with weight loss.   Eating wholegrain bread is associated with a reduction in all chronic disease and in increased lifespan.  I have written many blogs on the health benefits of whole grains and specifically whole grain bread. 

Sauerkraut

Sauerkraut is one of the oldest traditional foods, with very long roots in German, Russian, and Chinese cuisine, dating back 2,000 years or more. Sauerkraut means “sour cabbage” in German, although the Germans weren’t actually the first to make sauerkraut. (It’s believed the Chinese were.)⁵⁴ 

Hippocrates described sauerkraut as a health food and medicinal remedy in his writing. The Romans have also valued the beneficial effect of sauerkraut. The writer Plinius Secundus wrote, “The cabbage helps to provide plenty of milk for breastfeeding mothers, it helps for cloudy eyes, positively affects headaches and is supposed to work as a cure after alcohol consumption.”⁵⁵  

Made from fermented green or red cabbage, sauerkraut is high in fiber, vitamin A, vitamin C, vitamin K, and B vitamins. It’s also a great source of iron, copper, calcium, sodium, manganese, and magnesium.

Is store-bought sauerkraut fermented? Not always, especially the canned/processed kind. Real, traditional, fermented sauerkraut needs to be refrigerated, is usually stored in glass jars and says that it is fermented on the package/label.

Epidemiological evidence suggests a significant decrease in breast cancer risk with high intake of sauerkraut during adolescence.⁵⁶   

Kimchi

Kimchi is a traditional fermented Korean dish that is made from vegetables, including cabbage, plus spices like ginger, garlic, pepper, and other seasoning. It’s often added to Korean recipes like rice bowls, ramen, or bibimbap.

Kimchi consumption has been associated with various health benefits such as anti-inflammatory effects, prevention of atherosclerosis, improvements in cachexia associated with cancer, modulation of cholesterol and blood glucose, enhanced immunity, and atopic dermatitis prevention.

Other reported health benefits include improvements in cognitive impairments and hepatic damage inflicted by high cholesterol levels. Kimchi also alleviates symptoms of IBS and is possibly linked to inhibiting cancer cell growth in various cancers.⁵⁷  

Traditional Fermented Soybean Products

The production and consumption of fermented soy foods, including natto, miso, douchi, cheonggukjang, doenjang, tempeh, and fermented soy milk are widespread in Asian countries. These foods have emerged as an important part of people’s dietary structure because of the unique flavors and improved health benefits. 

During fermentation, the nutrients in soybean undergo a series of biochemical reactions catalyzed naturally by microorganism secreted enzymes. Fermentation increases the content of ingredients originally contained in soybeans and adds new ingredients that are not present in the original soybeans. Thereafter, many functional and bioactive substances such as bioactive peptides, unsaturated fatty acids, free soy isoflavones, vitamins and minerals are produced, making fermented soy products more advantageous in nutrition and health.⁵⁸   

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.^59,60   

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.⁶¹   

Mechanisms by which fermented soy foods affect diabetes⁶²   

Miso

Miso is created by fermenting soybeans, barley, or brown rice with koji, a type of fungus. It’s a traditional Japanese ingredient in recipes including miso soup. It’s been a staple in Chinese and Japanese diets for approximately 2,500 years. Miso consumption attenuates sympathetic nerve activity, resulting in lowered blood pressure and heart rate.⁶³  

Ingestion of Miso Regulates Immunological Robustness in Mice⁶⁴   

Consumption of miso soup is inversely associated with the risk of breast cancer.⁶⁵    

Miso-Carrot-Ginger Salad Dressing

2 tablespoons sesame seed oil (non-toasted)

1 tablespoon toasted sesame oil

2 oz. of rice vinegar

3 tablespoons white miso

2 medium carrots, peeled and cut into small pieces

1 inch ginger root, peeled and cut into small pieces, or use 1-2 tsp. of ginger juice

1 clove of garlic

1 -2 teaspoons raw honey

1 tsp. tamari 

¼ tsp. Turmeric powder

salt and pepper (white or black), to taste

Blend in blender and serve

Tempeh

Another beneficial fermented food made with soybeans is tempeh, a product that is created by combining soybeans with a tempeh starter, which is a mix of live mold (Tempeh is usually made from soybeans fermented with Rhizopus oligoporus fungal species).⁶⁶   When it sits for a day or two, this results in it becoming a dense, cake-like product that contains both probiotics and a hefty dose of protein, too. Tempeh has a spongy and more “grainy” even meat-like texture, compared to tofu.

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.⁶⁷    

Tempeh is a probiotic food that influences your gut microbiome. Your gut microbiota are the bacteria that reside in your digestive system. It also seems to be rich in prebiotics — types of fiber that promote the growth of beneficial bacteria in your digestive system.⁶⁸   

Donnie’s Lemon Broiled Tempeh

This is one of my favorite tempeh recipes. I created it several years ago, and enjoy it at least a couple of times a month. Toasted sesame oil adds a rich, nutty flavor; coconut oil is equally good and adds an Indonesian flavor to the dish. I like to serve this over steamed brown basmati or black rice. Serves 4. 

Ingredients:

Marinade:

2 freshly squeezed lemons

1 tsp. fresh lemon peel

2 tbsp. toasted sesame seed oil 

2 tbsp. untoasted sesame seed oil (or melted coconut oil)

1 12-ounce package tempeh

2 tbsp. tamari

2-3 minced cloves of garlic

1 tbsp. maple syrup

Dash of ground pepper (black and/or crushed red pepper)

Additional Options: 1-2 tsp. Za’atar, 1 tbsp. fresh sliced ginger, 1-2 tablespoons coconut milk

Vegetables: 

3 medium zucchini, sliced

2 cups shitake mushrooms, sliced

1 red pepper, cut into bite-sized pieces

1 large sliced onion

Optional: 1 sliced carrot

Directions:

1. Combine all ingredients in a glass baking dish, cover, and marinate overnight in the refrigerator. 

2. When ready to cook, preheat oven to 400 degrees F.

3. Transfer tempeh, vegetables, and sauce to a heavy broiling pan. Bake in preheated oven for 30 minutes.  

4. Stir occasionally to prevent sticking. At the end of baking time, finish by broiling for 10 minutes. 

5. Serve over brown or black rice.

Apple Cider Vinegar

Apple cider vinegar that is raw and contains “the mother” is fermented and does contain some probiotics. It also contains certain types of acids like acetic acid, which supports the function of probiotics and prebiotics in your gut. However, most vinegars available in the supermarket do not contain probiotics.

Regularly consuming apple cider vinegar can help to regulate blood pressure.^69,70   

Apple Cider Vinegar (ACV) improves mood and reduces depression and anxiety

Vinegar is a natural product derived from fruits or grains after being subjected to food fermentation processes. Vinegar is one of the most widely used acidic condiments. Recently, rapid advances have been made in the area of vinegar research. Vinegar can be made either naturally, through alcoholic and then acetic acid fermentation, or artificially, in laboratories. Vinegar is the product of acetic acid fermentation of dilute alcoholic solutions, manufactured by a two-step process. The first step is the production of ethanol from a carbohydrate source such as glucose, which is carried out by yeasts. The second step is the oxidation of ethanol to acetic acid, which is carried out by acetic acid bacteria.

Vinegar is a beneficial food additive, preservative, and condiment. It is appreciated across the Islamic world following the Prophetic teaching where Prophet Muhammad (peace be upon him) recommended its utility, saying: “The best of condiments is vinegar.” Different types of traditional vinegar are available around the globe and have many applications. Modern medicine recognizes the health benefits, especially upon metabolism and circulation, mediated by the bioactive constituents of vinegar, including acetic acid, caffeic acid, ferulic acid, chlorogenic acid, gallic acid, p-coumaric acid, catechin, and epicatechin.^71,72   

A study published in the Journal of Functional Foods found that consuming ACV led to reduced anxiety-like behavior in rats.⁷³    Another study in the European Journal of Clinical Nutrition suggested that vinegar consumption could help reduce the glycemic response to a meal, which may indirectly influence mood and anxiety levels.⁷⁴   

Daily vinegar ingestion has been linked to improved glycemic control, but recent data suggest a separate unexplored role for vinegar in mental health. Utilizing a placebo-controlled, parallel arm study design, this 4-week trial examined the impact of daily vinegar ingestion on mood states and urinary metabolites in healthy college students. Participants were randomized to the vinegar group (VIN: n = 14; 1.5 g acetic acid/day as liquid vinegar) or the control group (CON: n = 11; 0.015 g acetic acid/day as a pill) with no change to customary diet or physical activity. At baseline and at study week four, participants completed the Profile of Mood States (POMS) and the Center for Epidemiological Studies-Depression (CES-D) questionnaires and provided a first-morning urine sample for targeted metabolomics analyses. The change in both POMS depression scores and CES-D scores differed significantly between groups favoring improved affect in the VIN versus CON participants after four weeks. Metabolomics analyses pre and post-intervention suggested metabolite alterations associated with vinegar ingestion that are consistent for improved mood, including enzymatic dysfunction in the hexosamine pathway as well as significant increases in glycine, serine, and threonine metabolism. These data warrant continued investigation of vinegar as a possible agent to improve mood state.⁷⁵   

A randomized controlled study examined the 4-week change in scores for the Center for Epidemiological Studies Depression (CES-D) questionnaire and the Patient Health Questionnaire (PHQ-9) in healthy overweight adults ingesting 2.95 g acetic acid (4 tablespoons vinegar) vs. 0.025 g acetic acid (one vinegar pill) daily. A secondary objective explored possible underlying mechanisms using metabolomics analyses. At week four, mean CES-D scores fell 26% and 5% for VIN and CON participants respectively, a non-significant difference between groups, and mean PHQ-9 scores fell 42% and 18% for VIN and CON participants (p = 0.036). Metabolomics analyses revealed increased nicotinamide concentrations and upregulation of the NAD+ salvage pathway for VIN participants compared to controls, metabolic alterations previously linked to improved mood. Thus, daily vinegar ingestion over four weeks improved self-reported depression symptomology in healthy overweight adults, and enhancements in niacin metabolism may factor into this improvement.⁷⁶   

Anti-obesity effect of apple cider vinegar 

Aim of the study: The search of new anti-obesogenic treatments based on medicinal plants without or with minimal side effects is a challenge. In this context, the present study was conducted to evaluate the anti-obesogenic effect of apple cider vinegar (ACV) in Wistar rats subjected to a high fat diet.

Materials and methods: Eighteen male Wistar rats (140±5g) were divided into three equal groups. A witness group submitted to standard laboratory diet and two groups subjected to a high fat diet (cafeteria diet); one received a daily gavage of apple cider vinegar (7mL/kg/d) for 30 days. Throughout the experiment monitoring the nutritional assessment, anthropometric, and biochemical parameters is achieved.

Results: In the RCV vs RC group, we observed a highly significant decrease (P<0.001) in body weight and food intake. On the other hand, the VCP decreases very significantly different anthropometric parameters: BMI (P<0.01), chest circumference and abdominal circumference (P<0.001), decreases serum glucose levels (26.83%) and improves the serum lipid profile by reducing plasma levels of total cholesterol (34.29%), TG (51.06%), LDL-c (59.15%), VLDL (50%) and the total lipid (45.15%), and increasing HDL-c (39.39%), thus offering protection against atherogenic risk (61.62%).

Conclusion: This preliminary study indicates that the metabolic disorders caused by high fat diet (cafeteria) are thwarted by taking apple cider vinegar which proves to have a satiating effect, antihyperlipidemic and hypoglycemic effects, and seems prevent the atherogenic risk.⁷⁷   

In a recent study there was a significant dose-response relationship between the amount of vinegar consumed by 12 healthy subjects and their glucose and insulin responses to white bread. Vinegar reduces the body’s insulin response to a carbohydrate meal.⁷⁸  

You can add one tablespoon of apple cider vinegar to a drink twice a day. Before breakfast and lunch or breakfast and dinner, add one tablespoon of apple cider vinegar in your meal, and then start consuming more fermented vegetables like sauerkraut and kimchi or drinking kvass to really boost probiotic levels.

Donnie’s Pickled Onion Recipe

1 large organic red onion, cut in half and then thinly sliced. Put in a medium size saucepan.

Add the following:

• 4 oz. Water 
• 3 oz. Vinegar (I find a mixture of organic red wine vinegar and organic seasoned rice vinegar 
• ¼ tsp. Real or Pink salt 
• Garam Marsala Indian spice mix ½ tsp. Garam Marsala is a blend of warming, aromatic spices 
• 1 Bay leaf 
• 2-3 cloves or a pinch of clove powder
• 1 Tbls. Raw honey
• Turn the stove on and bring to a light boil for no more than 1 minute.
• Let cool and put into an 8 oz. mason jar

Refrigerate and in 24 hours you are ready to enjoy them – I add a forkful to my nightly salad.

They will last up to 2 weeks in the refrigerator, but I doubt you won’t have them all eaten before that.

Pickles

Didn’t think that pickles had probiotics? Fermented pickles contain a ton of vitamins and minerals, plus antioxidants and gut-friendly probiotic bacteria. Pickling foods such as cucumbers involves preserving cucumbers in salt, with or without tangy acid, like vinegar, and other possible ingredients, such as a sugar/sweetener and seasonings.

Most store-bought pickles are made with vinegar and cucumbers, and although this makes the pickles taste sour, this doesn’t lead to natural fermentation. Fermented pickles should be made with cucumbers and brine (salt + water). Pickles made by fermentation form naturally occurring bacteria producing lactic acid, which gives pickles their characteristic sourness.⁷⁹  

What is the best brand of pickles if you want probiotics? When choosing a jar of pickles, look for “lactic acid fermented pickles” made by a manufacturer that uses organic products and brine, refrigerates the pickles, and states that the pickles have been fermented. If you can find a local maker, such as at a farmers’ market, you’ll get some of the best probiotics for your health.

Pickle juice is a great source of electrolytes and a cure for leg cramps

Up to 60% of adults experience the pain and discomfort of nightly leg cramps according to research in the journal American Family Physician.⁸⁰    

It turns out that a specific ingredient in pickle juice, called acetic acid, found in the vinegar used to make pickles, may be the main contributing compound that alleviates leg cramps. “Acetic acid appears to calm down nerve cells. Acetic acid enhances communication between neurons and muscles, which then helps legs muscles relax. There is a relationship between the acetic acid and the electrolytes unique to pickle juice that makes the medicine. 

A recent study sought to determine whether pickle juice can improve muscle cramp severity in patients with cirrhosis. This study enrolled 82 patients with cirrhosis and a history of >4 muscle cramps in the previous month from December 2020 to December 2021. Patients were randomized 1:1 to sips of pickle juice vs tap water at cramp onset. Our primary outcome assessed at 28 days was the change in cramp severity measured by the visual analog scale for cramps (VAS-cramps, scaled 0-10). Cramps were assessed 10 times over 28 days using interactive text messages. Secondary outcomes included the proportion of days with VAS-cramps <5, change in sleep quality, and global health-related quality of life measured using the EQ-5D.

Overall, 74 patients completed the trial, aged 56.6 ± 11.5 years, 54% male, 41% with ascites, 38% with encephalopathy, and model for end-stage liver disease-sodium score 11.2 ± 4.9. Many patients were receiving other cramp therapies at baseline. The baseline VAS for cramps was 4.2 ± 3.4, the EQ-5D was 0.80 ± 0.10, and 43% rated sleep as poor. At trial completion, the respective values for the pickle juice and control arms were -2.25 ± 3.61 points on the VAS for cramps, compared with control tap water (-0.36 ± 2.87), P = 0.03; a proportion of cramp-days with VAS-cramps <5 were 46% vs 35% (P = 0.2); and the change in sleep quality was not different (P = 0.1). The end-of-trial EQ-5D was 0.78 ± 0.10 vs 0.80 ± 0.10 (P = 0.3). No differences in weight change were observed for those with and without ascites. According to this study, sips of pickle brine consumed at cramp onset improve cramp severity without adverse events.⁸¹    You want to drink 1 to 2 ounces of the juice to both prevent and relieve leg cramps.

Natural Compounds, Medicinal Plants, and Mushrooms on the Gut Microbiota in Colitis and Cancer

Various medicinal botanicals have reported anti-cancer and/or anti-inflammatory properties. Preclinical studies have illustrated that some of these natural products are also capable of modulating the gut microbiota, suggesting their use as a possible alternative approach to improve gut dysbiosis and thereby assist disease treatment. In this review article, we have summarized the current knowledge on the effects of natural compounds, medicinal plants, and mushrooms on the gut microbiota in various cancers and colitis in preclinical animal models. 

References

1. Yu AQ, Li L. The Potential Role of Probiotics in Cancer Prevention and Treatment. Nutr Cancer. 2016 May­Jun;68(4):535­44. doi: 10.1080/01635581.2016.1158300. Epub 2016 May 4.
2. Malczewski AB, Ketheesan N, Coward JIG, Navarro S. Enhancing Checkpoint Inhibitor Therapy in Solid Tissue Cancers: The Role of Diet, the Microbiome & Microbiome-Derived Metabolites. Front Immunol. 2021 Jul 7;12:624434. doi: 10.3389/fimmu.2021.624434. PMID: 34305883; PMCID: PMC8293987.
3. Yeung CY, Chan WT, Jiang CB, Cheng ML, Liu CY, Chang SW, Chiang Chiau JS, Lee HC. Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model. PLoS One. 2015 Sep 25;10(9):e0138746. doi: 10.1371/journal.pone.0138746. Erratum in: PLoS One. 2015;10(10):e0141402. PMID: 26406888; PMCID: PMC4583404.
4. Pepoyan AZ, Manvelyan AM, Balayan MH, McCabe G, Tsaturyan VV, Melnikov VG, Chikindas ML, Weeks R, Karlyshev AV. The Effectiveness of Potential Probiotics Lactobacillus rhamnosus Vahe and Lactobacillus delbrueckii IAHAHI in Irradiated Rats Depends on the Nutritional Stage of the Host. Probiotics Antimicrob Proteins. 2020 Dec;12(4):1439-1450. doi: 10.1007/s12602-020-09662-7. PMID: 32462507.
5. Fijan S, Frauwallner A, Langerholc T, Krebs B, Ter Haar Née Younes JA, Heschl A, Mičetić Turk D, Rogelj I. Efficacy of Using Probiotics with Antagonistic Activity against Pathogens of Wound Infections: An Integrative Review of Literature. Biomed Res Int. 2019 Dec 12;2019:7585486. doi: 10.1155/2019/7585486. PMID: 31915703; PMCID: PMC6930797.
6. Muro Urista C., Álvarez Fernández R., Riera Rodriguez F., Arana Cuenca A., Téllez Jurado A. Review: Production and functionality of active peptides from milk. Food Sci. Technol. Int. 2011;17:293–317. doi: 10.1177/1082013211398801. 
7. Yasuda S., Kuwata H., Kawamoto K., Shirakawa J., Atobe S., Hoshi Y., Yamasaki M., Nishiyama K., Tachibana H., Yamada K., et al. Effect of highly lipolyzed goat cheese on HL-60 human leukemia cells: Antiproliferative activity and induction of apoptotic DNA damage. J. Dairy Sci. 2012;95:2248–2260. doi: 10.3168/jds.2011-4153.
8. Swain MR, Anandharaj M, Ray RC, Parveen Rani R. Fermented fruits and vegetables of Asia: a potential source of probiotics. Biotechnol Res Int. 2014;2014:250424. doi: 10.1155/2014/250424. Epub 2014 May 28. PMID: 25343046; PMCID: PMC4058509.
9. Armstrong, H., Bording-Jorgensen, M., Dijk, S., and Wine, E. (2018). The complex interplay between chronic inflammation, the microbiome, and cancer: understanding disease progression and what we can do to prevent it. Cancers 10, E83. doi: 10.3390/cancers10030083
10. Di Domenico, E. G., Cavallo, I., Pontone, M., Toma, L., and Ensoli, F. (2017). Biofilm producing Salmonella Typhi: chronic colonization and development of gallbladder cancer. Int. J. Mol. Sci. 18, 1887. doi: 10.3390/ijms18091887
11. Helmink, B. A., Khan, M. A. W., Hermann, A., Gopalakrishnan, V., and Wargo, J. A. (2019). The microbiome, cancer, and cancer therapy. Nat. Med. 25, 377–388. doi: 10.1038/s41591-019-0377-7
12. Castellone V, Bancalari E, Rubert J, Gatti M, Neviani E, Bottari B. Eating Fermented: Health Benefits of LAB-Fermented Foods. Foods. 2021 Oct 31;10(11):2639. doi: 10.3390/foods10112639. PMID: 34828920; PMCID: PMC8620815.
13. Lazar V, Ditu LM, Pircalabioru GG, Gheorghe I, Curutiu C, Holban AM, Picu A, Petcu L, Chifiriuc MC. Aspects of Gut Microbiota and Immune System Interactions in Infectious Diseases, Immunopathology, and Cancer. Front Immunol. 2018 Aug 15;9:1830. doi: 10.3389/fimmu.2018.01830.
14. Malczewski AB, Ketheesan N, Coward JIG, Navarro S. Enhancing Checkpoint Inhibitor Therapy in Solid Tissue Cancers: The Role of Diet, the Microbiome & Microbiome-Derived Metabolites. Front Immunol. 2021 Jul 7;12:624434. doi: 10.3389/fimmu.2021.624434. PMID: 34305883; PMCID: PMC8293987.
15. Garnås E. Fermented Vegetables as a Potential Treatment for Irritable Bowel Syndrome. Curr Dev Nutr. 2023 Feb 18;7(3):100039. doi: 10.1016/j.cdnut.2023.100039. PMID: 37181929; PMCID: PMC10111609.
16. Swain MR, Anandharaj M, Ray RC, Parveen Rani R. Fermented fruits and vegetables of Asia: a potential source of probiotics. Biotechnol Res Int. 2014;2014:250424. doi: 10.1155/2014/250424. Epub 2014 May 28. PMID: 25343046; PMCID: PMC4058509.
17. George F., Daniel C., Thomas M., Singer E., Guilbaud A., Tessier F.J., Revol-Junelles A.M., Borges F., Foligné B. Occurrence and dynamism of lactic acid bacteria in distinct ecological niches: A multifaceted functional health perspective. Front. Microbiol. 2018;9:2899. doi: 10.3389/fmicb.2018.02899.
18. Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science http://dx.doi.org/10.1126/science.aan4236 (2017)
19. Liu YW, Liong MT, Chung YE, et al. Effects of Lactobacillus plantarum PS128 on children with autism spectrum disorder in Taiwan: A randomized, double-blind, placebo-controlled trial. Nutrients. 2019;11(4):820. doi:10.3390/nu11040820
20. Behera SS, Ray RC, Zdolec N. Lactobacillus plantarum with functional properties: An approach to increase safety and shelf-life of fermented foods. Biomed Res Int. 2018;2018:9361614. doi:10.1155/2018/9361614
21. Naito Y, Uchiyama K, Takagi T. A next-generation beneficial microbe: Akkermansia muciniphila. J Clin Biochem Nutr. 2018 Jul;63(1):33-35. doi: 10.3164/jcbn.18-57. Epub 2018 Jun 20. PMID: 30087541; PMCID: PMC6064808
22. Fan S, Jiang Z, Zhang Z, Xing J, Wang D, Tang D. Akkermansia muciniphila: a potential booster to improve the effectiveness of cancer immunotherapy. J Cancer Res Clin Oncol. 2023 Nov;149(14):13477-13494. doi: 10.1007/s00432-023-05199-8. Epub 2023 Jul 25. PMID: 37491636.
23. Ansaldo E, Slayden LC, Ching KL, Koch MA, Wolf NK, Plichta DR, Brown EM, Graham DB, Xavier RJ, Moon JJ, Barton GM. Akkermansia muciniphila induces intestinal adaptive immune responses during homeostasis. Science. 2019 Jun 21;364(6446):1179-1184. doi: 10.1126/science.aaw7479. PMID: 31221858; PMCID: PMC6645389.
24. Fang J, Zhang H, Zhang X, Lu X, Liu J, Li H, Huang J. Akkermansia muciniphila improves gastric cancer treatment by modulating the immune microenvironment. Future Microbiol. 2024;19(6):481-494. doi: 10.2217/fmb-2023-0210. Epub 2024 Apr 17. PMID: 38629914; PMCID: PMC11216265.
25. Zhou K. Strategies to promote abundance of Akkermansia muciniphila, an emerging probiotics in the gut, evidence from dietary intervention studies. J Funct Foods. 2017;33:194-201. doi:10.1016/j.jff.2017.03.045
26. Roopchand DE, Carmody RN, Kuhn P, et al. Dietary polyphenols promote growth of the gut bacterium Akkermansia muciniphila and attenuate high-fat diet-induced metabolic syndrome. Diabetes. 2015;64:2847–2858. doi: 10.2337/db14-1916
27. Reunanen J, Kainulainen V, Huuskonen L, et al. Akkermansia muciniphila adheres to enterocytes and strengthens the integrity of the epithelial cell layer. Appl Environ Microbiol. 2015;81:3655–3662. doi: 10.1128/AEM.04050-14.
28. Anhê FF, Marette A. A microbial protein that alleviates metabolic syndrome. Nat Med. 2017;23:11–12. doi: 10.1038/nm.4261.
29. Anhê FF, Pilon G, Roy D, Desjardins Y, Levy E, Marette A. Triggering Akkermansia with dietary polyphenols: A new weapon to combat the metabolic syndrome? Gut Microbes. 2016;7(2):146-53. doi: 10.1080/19490976.2016.1142036. Erratum in: doi: 10.1136/gutjnl-2014-307142. PMID: 26900906; PMCID: PMC4856456.
30. Pierre JF, Heneghan AF, Feliciano RP, Shanmuganayagam D, Roenneburg DA, Krueger CG, Reed JD, Kudsk KA. Cranberry proanthocyanidins improve the gut mucous layer morphology and function in mice receiving elemental enteral nutrition. JPEN J Parenter Enter Nutr 2013; 37:401-9; PMID:23064255; http://dx.doi.org/ 10.1177/0148607112463076
31. Anhê FF, Roy D, Pilon G, Dudonné S, Matamoros S, Varin TV, Garofalo C, Moine Q, Desjardins Y, Levy E, Marette A. A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut. 2015 Jun;64(6):872-83. doi: 10.1136/gutjnl-2014-307142. Epub 2014 Jul 30. PMID: 25080446.
32. Dong C, Yu J, Yang Y, Zhang F, Su W, Fan Q, Wu C, Wu S. Berberine, a potential prebiotic to indirectly promote Akkermansia growth through stimulating gut mucin secretion. Biomed Pharmacother. 2021 Jul;139:111595. doi: 10.1016/j.biopha.2021.111595. Epub 2021 Apr 14. PMID: 33862492. 
33. Jeong HW, Kim JK, Kim AY, Cho D, Lee JH, Choi JK, Park M, Kim W. Green Tea Encourages Growth of Akkermansia muciniphila. J Med Food. 2020 Aug;23(8):841-851. doi: 10.1089/jmf.2019.4662. Epub 2020 Jun 25. PMID: 32598202.
34. Wu H, Liu J, Zhang XH, Jin S, Li P, Liu H, Zhao L, Wang J, Zhao S, Tian HD, Lai JR, Hao Y, Liu GR, Hou K, Yan M, Liu SL, Pang D. The combination of flaxseed lignans and PD-1/ PD-L1 inhibitor inhibits breast cancer growth via modulating gut microbiome and host immunity. Drug Resist Updat. 2025 May;80:101222. doi: 10.1016/j.drup.2025.101222. Epub 2025 Feb 28. PMID: 40048957.
35. Xiao, M., Zhang, C., Duan, H. et al. Cross-feeding of bifidobacteria promotes intestinal homeostasis: a lifelong perspective on the host health. npj Biofilms Microbiomes 10, 47 (2024). https://doi.org/10.1038/s41522-024-00524-6
36. Rosa DD, Dias MMS, Grześkowiak ŁM, Reis SA, Conceição LL, Peluzio MDCG. Milk kefir: nutritional, microbiological and health benefits. Nutr Res Rev. 2017 Jun;30(1):82-96. doi: 10.1017/S0954422416000275. Epub 2017 Feb 22. PMID: 28222814.
37. Slattery C, Cotter PD, O’Toole PW. Analysis of Health Benefits Conferred by Lactobacillus Species from Kefir. Nutrients. 2019 Jun 1;11(6):1252. doi: 10.3390/nu11061252. PMID: 31159409; PMCID: PMC6627492.
38. Farag MA, Jomaa SA, El-Wahed AA, El-Seedi AHR. The Many Faces of Kefir Fermented Dairy Products: Quality Characteristics, Flavour Chemistry, Nutritional Value, Health Benefits, and Safety. Nutrients. 2020 Jan 28;12(2):346. doi: 10.3390/nu12020346. PMID: 32013044; PMCID: PMC7071183.
39. Kadooka Y, Sato M, Imaizumi K, et al. Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial.
40. Kang JH, Yun SI, Park MH, Park JH, Jeong SY, Park HO. Anti-obesity effect of Lactobacillus gasseri BNR17 in high-sucrose diet-induced obese mice. PLoS One. 2013;8(1):e54617. doi: 10.1371/journal.pone.0054617. Epub 2013 Jan 30. PMID: 23382926; PMCID: PMC3559800.
41. Kim J, Yun JM, Kim MK, Kwon O, Cho B. Lactobacillus gasseri BNR17 Supplementation Reduces the Visceral Fat Accumulation and Waist Circumference in Obese Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. J Med Food. 2018 May;21(5):454-461. doi: 10.1089/jmf.2017.3937. Epub 2018 Apr 24. PMID: 29688793.
42. Ooi LG, Ahmad R, Yuen KH, Liong MT. Lactobacillus gasseri [corrected] CHO-220 and inulin reduced plasma total cholesterol and low-density lipoprotein cholesterol via alteration of lipid transporters.
43. Ene A, Stegman N, Wolfe A, Putonti C. Genomic insights into Lactobacillus gasseri and Lactobacillus paragasseri. PeerJ. 2022 Jun 7;10:e13479. doi: 10.7717/peerj.13479. PMID: 35694384; PMCID: PMC9186330.
44. Itoh H, Uchida M, Sashihara T. Lactobacillus gasseri OLL2809 is effective especially on the menstrual pain and dysmenorrhea in endometriosis patients: randomized, double-blind, placebo-controlled study.
45. Lee SH, Lim TJ, Yun EJ, Kim KH, Lim S. Anti-Menopausal Effect of Soybean Germ Extract and Lactobacillus gasseri in the Ovariectomized Rat Model. Nutrients. 2023 Oct 23;15(20):4485. doi: 10.3390/nu15204485. PMID: 37892560; PMCID: PMC10609938.
46. Ryuzo Deguchi, Hidemasa Nakaminami, Emiko Rimbara, et al. Effect of pretreatment with Lactobacillus gasseri OLL2716 on first-line Helicobacter pylori eradication therapy.
47. Chen YS, Jan RL, Lin YL, Chen HH, Wang JY. Randomized placebo-controlled trial of lactobacillus on asthmatic children with allergic rhinitis.
48. Gao X, Jia HY, Chen GC, Li CY, Hao M. Yogurt Intake Reduces All-Cause and Cardiovascular Disease Mortality: A Meta-Analysis of Eight Prospective Cohort Studies. Chin J Integr Med. 2020 Jun;26(6):462-468. doi: 10.1007/s11655-020-3085-8. Epub 2020 Jan 22. PMID: 31970674.
49. Chen HC, Wang SY, Chen MJ. Microbiological study of lactic acid bacteria in kefir grains by culture-dependent and culture-independent methods. Food Microbiol. 2008 May;25(3):492-501. doi: 10.1016/j.fm.2008.01.003. Epub 2008 Jan 29. PMID: 18355674.
50. Carasi P, Díaz M, Racedo SM, De Antoni G, Urdaci MC, Serradell Mde L. Safety characterization and antimicrobial properties of kefir-isolated Lactobacillus kefiri. Biomed Res Int. 2014;2014:208974. doi: 10.1155/2014/208974. Epub 2014 May 13. PMID: 24955346; PMCID: PMC4052788.
51. Kong CY, Li ZM, Mao YQ, Chen HL, Hu W, Han B, Wang LS. Probiotic yogurt blunts the increase of blood pressure in spontaneously hypertensive rats via remodeling of the gut microbiota. Food Funct. 2021 Oct 19;12(20):9773-9783. doi: 10.1039/d1fo01836a. PMID: 34494630.
52. Aldrete-Tapia A, Escobar-Ramírez CM, Tamplin ML, Hernández-Iturriaga M. Characterization of Bacterial Communities in Mexican Artisanal Raw Milk “Bola de Ocosingo” Cheese by High-Throughput Sequencing. Front Microbiol. 2018 Oct 29;9:2598. doi: 10.3389/fmicb.2018.02598. PMID: 30420851; PMCID: PMC6217346.
53. Lau SW, Chong AQ, Chin NL, Talib RA, Basha RK. Sourdough Microbiome Comparison and Benefits. Microorganisms. 2021 Jun 23;9(7):1355. doi: 10.3390/microorganisms9071355. PMID: 34201420; PMCID: PMC8306212.
54. Raak C, Ostermann T, Boehm K, Molsberger F. Regular consumption of sauerkraut and its effect on human health: a bibliometric analysis. Glob Adv Health Med. 2014 Nov;3(6):12-8. doi: 10.7453/gahmj.2014.038. PMID: 25568828; PMCID: PMC4268643.
55. C. Plinius Secundus d. Ä.: Naturkunde Latein-Deutsch. München:: Artemis-Verlag; 1973.
56. Dr Pathak, JP He, J Charzewska, Joint Association of High Cabbage/Sauerkraut Intake at 12-13 Years of Age and Adulthood with Reduced Breast Cancer Risk in Polish Migrant Women: Results from the US Component of the Polish Women’s Health Study (PWHS). (Michigan State University, E. Lansing, MI 48824 and University of New Mexico, Albuquerque, NM 87131, National Food and Nutrition Institute, Warsaw, PL) 2014
57. Song, E. et al. (2023) “Effects of kimchi on human health: a scoping review of randomized controlled trials,” Journal of Ethnic Foods, 10(1). doi: 10.1186/s42779-023-00173-8. https://journalofethnicfoods.biomedcentral.com/articles/10.1186/s42779-023-00173-8
58. Liu L, Chen X, Hao L, Zhang G, Jin Z, Li C, Yang Y, Rao J, Chen B. Traditional fermented soybean products: processing, flavor formation, nutritional and biological activities. Crit Rev Food Sci Nutr. 2022;62(7):1971-1989. doi: 10.1080/10408398.2020.1848792. Epub 2020 Nov 23. PMID: 33226273.
59. Hashimoto Y, Hamaguchi M, Fukui M. Fermented soybean foods and diabetes. J Diabetes Investig. 2023 Oct 6. doi: 10.1111/jdi.14088. Epub ahead of print. PMID: 37799064.
60. Babu PD, Bhakyaraj R, Vidhyalakshmi R. A low cost nutritious food “tempeh” – a review. World J Dairy Food Sci 2009; 4: 22–27.
61. Hashimoto Y, Hamaguchi M, Fukui M. Microbe-associated metabolites as targets for incident type 2 diabetes. J Diabetes Investig 2021; 12: 476–478.
62. Hashimoto Y, Hamaguchi M, Fukui M. Fermented soybean foods and diabetes. J Diabetes Investig. 2023 Oct 6. doi: 10.1111/jdi.14088. Epub ahead of print. PMID: 37799064.
63. Ito K. Review of the health benefits of habitual consumption of miso soup: focus on the effects on sympathetic nerve activity, blood pressure, and heart rate. Environ Health Prev Med. 2020 Aug 31;25(1):45. doi: 10.1186/s12199-020-00883-4. PMID: 32867671; PMCID: PMC7461326.
64. Kotake K, Kumazawa T, Nakamura K, Shimizu Y, Ayabe T, Adachi T. Ingestion of miso regulates immunological robustness in mice. PLoS One. 2022 Jan 21;17(1):e0261680. doi: 10.1371/journal.pone.0261680. PMID: 35061718; PMCID: PMC8782471
65. Fujimaki S, Hayashi K. Re: Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst. 2003 Dec 17;95(24):1881-2; author reply 1881-2. doi: 10.1093/jnci/djg131. PMID: 14679159.
66. Nout M, Kiers J. Tempe fermentation, innovation and functionality: update into the third millenium. J Appl Microbiol 2005; 98: 789–805.
67. Abu-Salem FM, Mohamed R, Gibriel A, et al. Levels of some antinutritional factors in tempeh produced from some legumes and jojobas seeds. Int Sch Sci Res Innov 2014; 8: 296–301
68. Kuligowski M, Jasińska-Kuligowska I, Nowak J. Evaluation of bean and soy tempeh influence on intestinal bacteria and estimation of antibacterial properties of bean tempeh. Pol J Microbiol. 2013;62(2):189-94. PMID: 24053022.
69. Na L, Chu X, Jiang S, Li C, Li G, He Y, Liu Y, Li Y, Sun C. Vinegar decreases blood pressure by down-regulating AT1R expression via the AMPK/PGC-1α/PPARγ pathway in spontaneously hypertensive rats. Eur J Nutr. 2016 Apr;55(3):1245-53. doi: 10.1007/s00394-015-0937-7. Epub 2015 Oct 18. PMID: 26476634.
70. Kondo S, Tayama K, Tsukamoto Y, Ikeda K, Yamori Y. Antihypertensive effects of acetic acid and vinegar on spontaneously hypertensive rats. Biosci Biotechnol Biochem. 2001 Dec;65(12):2690-4. doi: 10.1271/bbb.65.2690. PMID: 11826965.
71. Khalifa SAM, El-Shabasy RM, Tahir HE, Abo-Atya DM, Saeed A, Abolibda TZ, Guo Z, Zou X, Zhang D, Du M, Kai G, Buccato DG, Daglia M, Zhao C, El-Seedi HR. Vinegar – a beneficial food additive: production, safety, possibilities, and applications from ancient to modern times. Food Funct. 2024 Sep 27. doi: 10.1039/d4fo02377c. Epub ahead of print. PMID: 39327882.
72. Chen GL, Zheng FJ, Lin B, Yang YX, Fang XC, Verma KK, Yang LF. Vinegar: A potential source of healthy and functional food with special reference to sugarcane vinegar. Front Nutr. 2023 Mar 16;10:1145862. doi: 10.3389/fnut.2023.1145862. PMID: 37006937; PMCID: PMC10061008.
73. Choi JI, Lee YL, Lee SY. Efficacy and safety of fermented Prunus mume vinegar on fatigue improvement in adults with unexplained fatigue: A randomized controlled trial. Front Nutr. 2022 Nov 9;9:990418. doi: 10.3389/fnut.2022.990418. PMID: 36438753; PMCID: PMC9682036.
74. Brighenti F, Castellani G, Benini L, Casiraghi MC, Leopardi E, Crovetti R, Testolin G. Effect of neutralized and native vinegar on blood glucose and acetate responses to a mixed meal in healthy subjects. Eur J Clin Nutr. 1995 Apr;49(4):242-7. PMID: 7796781.
75. Johnston CS, Jasbi P, Jin Y, Bauer S, Williams S, Fessler SN, Gu H. Daily Vinegar Ingestion Improves Depression Scores and Alters the Metabolome in Healthy Adults: A Randomized Controlled Trial. Nutrients. 2021 Nov 11;13(11):4020. doi: 10.3390/nu13114020. PMID: 34836275; PMCID: PMC8622118.
76. Barrong H, Coven H, Lish A, Fessler SN, Jasbi P, Johnston CS. Daily Vinegar Ingestion Improves Depression and Enhances Niacin Metabolism in Overweight Adults: A Randomized Controlled Trial. Nutrients. 2024 Jul 18;16(14):2305. doi: 10.3390/nu16142305. PMID: 39064748; PMCID: PMC11280469.
77. Bouderbala H, Kaddouri H, Kheroua O, Saidi D. Effet anti-obésogène du vinaigre de cidre de pomme chez le rat soumis à un régime hyperlipidique [Anti-obesogenic effect of apple cider vinegar in rats subjected to a high fat diet]. Ann Cardiol Angeiol (Paris). 2016 Jun;65(3):208-13. French. doi: 10.1016/j.ancard.2016.04.004. Epub 2016 May 18. PMID: 27209492.
78. Ostman, Elin, Vinegar reduces the body’s insulin response to a carbohydrate meal and increases satiety, European Journal of Clinical Nutrition (vol 59, issue 9, pp983-988), 07/09/2005, Lund University.
79. Behera, Sudhanshu; Sheikha, Aly; Hammami, Riadh, et al. Traditionally fermented pickles: How the microbial diversity associated with their nutritional and health benefits? Journal of Functional Foods. 2020;70:103971. doi:10.1016/j.jff.2020.103971
80. Richard E Allen, MD, and Karl A. Kirby, MD, Nocturnal Leg Cramps, Am Fam Physician. 2012;86(4):350-355
81. Tapper EB, Salim N, Baki J, Zhao Z, Sundaram V, Patwardhan V, Nikirk SJ. Pickle Juice Intervention for Cirrhotic Cramps Reduction: The PICCLES Randomized Controlled Trial. Am J Gastroenterol. 2022 Jun 1;117(6):895-901. doi: 10.14309/ajg.0000000000001781. Epub 2022 Apr 13. PMID: 35416793.
82. Cheung MK, Yue GGL, Chiu PWY, Lau CBS. A Review of the Effects of Natural Compounds, Medicinal Plants, and Mushrooms on the Gut Microbiota in Colitis and Cancer. Front Pharmacol. 2020;11:744. Published 2020 May 15. doi:10.3389/fphar.2020.00744

⁸²