Sience Evidence

AKM/AKK BIO Tech

Since its discovery in 2004, over 20 years of research and thousands of laboratory and clinical research articles have accumulated a great deal of scientific evidence for the entry of AKK bacterial products into our lives.

What are second generation probiotics? How are they different from first generation probiotics?

Second-generation probiotics, also known as new-generation probiotics, are new types of probiotics screened and cultivated through modern biotechnological means on the basis of first-generation probiotics (mainly lactobacilli and bifidobacteria). Compared with the first generation of probiotics, the second generation of probiotics has significantly improved in terms of efficacy, safety and adaptability, and is able to regulate the micro-ecological balance of the intestinal tract, enhance immunity, improve the function of the digestive system, and so on, to provide more comprehensive protection for human health.

What specific strains are listed as second generation probiotics?

Currently, the main strains classified as second-generation probiotics include the following:

Clostridium butyricum

A probiotic that produces caseinate, one of the representatives of the second generation of probiotics.

Akkermansia muciniphila

It has received much attention in recent years and is closely related to the gut mucus layer and metabolic health.

Faecalibacterium prausnitzii

One of the dominant bacteria in the intestinal tract with significant anti-inflammatory properties.

Some strains of the genus Bifidobacterium

Bifidobacterium longum subsp. longum, for example, is an upgraded version of traditional probiotics.

Some strains of the genus Lactobacillus

Lactobacillus acidophilus, for example, still has an important place among second-generation probiotics.

These strains are not all newly discovered microorganisms, but have been endowed with more defined health benefits through scientific research, distinguishing them from traditional first-generation probiotics.

What specific strains are listed as second generation probiotics?

The efficacy of second-generation probiotics is more diverse and targeted, mainly in the following areas:

Regulates intestinal microecological balance

The diversity and stability of the intestinal flora is maintained by competitively inhibiting the growth of harmful bacteria. For example, Clostridium typhimurium inhibits the colonization of harmful bacteria, and Ackermannia improves the intestinal environment by regulating the thickness of the mucus layer.

strengthen immunity

Stimulates immune cell activity and increases the body's resistance to pathogens. For example, Lactobacillus acidophilus enhances the immune response and helps fight infections.

Improvement of the functioning of the digestive system

It promotes food digestion and absorption, and relieves constipation, diarrhea and other indigestion symptoms. Bifidobacterium longum bifidum performs particularly well in this regard.

anti-inflammatory effect

By producing anti-inflammatory substances, it relieves intestinal inflammation and prevents diseases such as inflammatory bowel disease. Clostridium Pullorum is a prime example of this effect.

Regulation of metabolism

 affects energy metabolism and lipid metabolism and improves metabolic diseases such as obesity and diabetes. Ackermann's bacteria are closely associated with the improvement of metabolic diseases.

Summarize

Second-generation probiotics are new probiotics developed on the basis of first-generation probiotics, and the representative strains include Clostridium Typhimurium, Clostridium Ackermannii, Clostridium Pullorum, as well as some strains of Bifidobacterium and Lactobacillus. Their efficacy covers the regulation of intestinal microecology, enhancement of immunity, improvement of digestive function, anti-inflammatory and metabolic regulation, etc. Compared with traditional probiotics, they are more diversified and precise, and are able to provide more comprehensive support for human health.

What are first generation probiotics?

First-generation probiotics refer to the earliest probiotic strains discovered and applied, mainly including lactobacilli (e.g. Lactobacillus acidophilus) and bifidobacteria. These strains, usually derived from the human gut, were the starting point for probiotic research and application, and have played an important role in improving intestinal health.

Key features

The first generation of probiotics produce lactic acid through fermentation, which lowers the pH level in the intestines, thus inhibiting the growth of harmful bacteria and helping to maintain the micro-ecological balance of the intestines. They act on the intestines with a simple mechanism and belong to the initial stage of probiotic development.

Efficacy

First-generation probiotics offer a variety of health benefits, including:

  • improve digestion: Helps break down food and promotes nutrient absorption.
  • strengthen immunity: Supports immune system function by regulating the gut microbiota.
  • Prevention of intestinal problems: such as diarrhea and constipation, relieving intestinal discomfort. In addition, they produce vitamins (e.g., B vitamins) and enzymes that further promote good health.

Historic significance

The first generation of probiotics laid the foundation for probiotic research and applications. Although subsequent generations of probiotics have become more diverse in function and application, the discovery and use of first-generation probiotics has provided valuable lessons and insights into these advances. In conclusion, first-generation probiotics are early probiotic strains, represented by Lactobacillus and Bifidobacterium, that function by regulating the intestinal environment and are important for human health.

What are first generation probiotics?
What are first generation probiotics?

Why is AKK bacteria the star of second generation probiotics?

AKK bacteria (Akkermansia muciniphila) is regarded as the star of second generation probiotics, mainly because it has demonstrated a unique and important role in intestinal health, metabolic regulation, and the prevention of many diseases. Here are the specific reasons why:

1. Close association with metabolic diseases

  • AKK bacteria are closely associated with the onset and development of metabolic diseases such as obesity, diabetes, and cardiovascular disease. It has been found that people with higher abundance of AKK bacteria in their bodies are usually in a healthier metabolic state, while reduced AKK bacteria are associated with problems such as obesity and insulin resistance.
  • It provides important support for the prevention and amelioration of metabolic diseases by regulating energy metabolism and improving insulin sensitivity.

2. Maintenance of intestinal barrier function

  • AKK bacteria are able to break down mucus in the intestines and promote the renewal and maintenance of the mucus layer, thus enhancing the intestinal barrier function. This effectively prevents the invasion of harmful substances and pathogens and reduces the risk of intestinal inflammation.
  • This property allows AKK bacteria to play a key role in the prevention of gut-related diseases such as inflammatory bowel disease.

3. Anti-inflammatory and immunomodulatory effects

  • AKK bacteria have significant anti-inflammatory capacity, inhibiting the production of inflammatory factors and reducing the inflammatory response in the intestinal tract and other tissues.
  • It also regulates the immune system and helps maintain immune balance, which may be beneficial in preventing autoimmune diseases.

4. Potential anti-tumor effects

  • Recent studies have shown that AKK bacteria may positively impact the prevention and treatment of certain cancers by modulating the intestinal microecology and immune system, a potential that has further elevated its interest.

3. Anti-inflammatory and immunomodulatory effects

  • Compared to traditional probiotics such as Lactobacillus and Bifidobacterium, AKK bacteria, as second generation probiotics, show broader and deeper effects on metabolic health and intestinal barrier protection.
  • Its discovery has brought new breakthroughs in probiotic research, showing great application prospects.

Summarize

AKK bacteria have become the star bacteria in the second generation of probiotics due to their unique functions in metabolic regulation, intestinal barrier maintenance, anti-inflammation, immunomodulation and potential anti-tumor effects. These properties not only make it significant in maintaining health, but also make it attract the attention of scientific research and medical community, with broad development potential.

To date, are there any second-generation probiotics which have been approved for marketing in China?
What is the worldwide availability?

As of April 2020, China approved 137 health food products with probiotics as the main ingredient, and no second-generation efficacious probiotics have yet been approved for marketing in China.

Since its discovery in 2004, more than 20 years of laboratory and clinical research on AKK bacteria, a large number of scientific and clinical data to prove its safety and effectiveness, in 2022, the European Union and the United States, successively approved the commercialization of AKK bacteria products for sale.

What are the main benefits of scientifically proven AKK bacteria?

AKK bacteria (mucinophilic Ackermannia.Akkermansia muciniphila) has received much attention in recent years in the field of gut health and metabolic regulation. Below are the key scientifically proven effects of AKK bacteria, and the specific sources of the leading journals and academic conferences where this evidence has been published:

01

Improved metabolic health

  • Efficacy: AKK bacteria are negatively associated with obesity, diabetes, cardiovascular metabolic disease and low-grade inflammation. Studies have shown that oral administration of AKK bacteria improves metabolic disease symptoms in mice.
  • evidence：
    • A 2013 study found that AKK bacteria counts were significantly reduced in obese and type II diabetic mice and that symptoms improved with AKK bacteria supplementation.
    • Early High-Fat Diet Affects Learning and Cognitive Function in Mice by Reducing AKK Bacteria Abundance, Associated with Metabolic Health, 2019 Study Shows
    • In 2022, the European Commission approved the use of pasteurization-inactivated AKK bacteria to be placed on the market as a novel food product, demonstrating its potential application in metabolic health.
  • source：
    • Neuropsychopharmacology (2019)
    • European Commission Regulation (EU) 2022/168
02

Regulating the immune system

  • Efficacy: AKK bacteria have a potential function in inflammatory bowel disease (IBD) to reduce symptoms of enteritis, modulate the immune response, and potentially prevent bowel cancer.
  • evidence：
    • Research from Nanjing Medical University found that oral administration of inactivated AKK bacteria or its outer membrane protein Amuc_1100 can improve colitis symptoms and has the effect of preventing bowel cancer.
    • The German Cancer Research Center (DKFZ) has found that increasing the concentration of AKK bacteria in a mouse model of acromegaly (ALS) improves symptoms and prolongs survival.
  • source：
    • Neuropsychopharmacology (2019)
    • German Cancer Research Center (DKFZ) Study
03

Anti-obesity and diabetes

  • Efficacy: AKK bacteria ameliorate high-fat diet-induced intestinal mucosal barrier dysfunction and metabolic disorders.
  • evidence：
    • Supplementation of AKK bacteria by gavage significantly improved the symptoms of metabolic disorders in mice on a high-fat diet.
    • In a mouse model of type II diabetes, the combination of AKK bacteria and metformin enhanced the therapeutic effect.
  • source：

《Proceedings of the National Academy of Sciences》（《PNAS》）

04

Improvement of cognitive function

  • Efficacy: AKK bacteria are associated with cognitive dysfunction and supplementation with AKK bacteria may help improve cognitive function.
  • evidence：
    • A study by a team from Chengdu University of Traditional Chinese Medicine found that an early high-fat diet affected learning and cognitive function in mice by decreasing the abundance of AKK bacteria, and that the symptoms improved after supplementation with AKK bacteria.
  • source：
    • Neuropsychopharmacology (2019)
05

extend life

  • Efficacy: AKK bacteria are more abundant in the intestines of long-lived elderly people, and supplementation with AKK bacteria may help prolong life.
06

Improvement of intestinal barrier function

  • Efficacy: AKK bacteria enhance intestinal barrier function and reduce intestinal permeability.
07

Regulates intestinal flora

  • Efficacy: AKK bacteria can regulate the composition of intestinal flora and maintain intestinal ecological balance.
08

anti-inflammatory effect

  • Efficacy: AKK bacteria are anti-inflammatory and reduce inflammatory reactions.
09

Improving Autism Symptoms

  • Efficacy: AKK bacteria may be associated with improved autism symptoms.
10

Improvement of fatty liver

  • Efficacy: AKK bacteria may help improve non-alcoholic fatty liver disease (NAFLD).

What is the best way to choose between the live (prebiotic) and inactivated (postbiotic) types of AKK products?

Akkermansia muciniphila (hereinafter referred to as Akk bacteria) is a beneficial bacterium found in the human gut that has gained attention for its potential to improve metabolic health and enhance intestinal barrier function. Regarding whether to choose inactivated bacteria (usually referred to as pasteurized organisms) or live bacteria when supplementing with Akk bacteria, the following is a comparison of four aspects: benefits, scientific basis, risks, and mechanism of action.

Inactivated bacteria (pasteurized Akk bacteria)

Benefit

  • Improvement of metabolic parameters: Studies have shown that pasteurized Akk bacteria can boost insulin sensitivity and lower cholesterol levels, which is especially beneficial for obese and overweight people.
  • Strengthening the intestinal barrier: Promotes improved intestinal barrier function through its structural components that interact with the host.

Scientific basis

  • A human study (Depommier et al., 2019) found that pasteurized Akk bacteria were more effective than live bacteria in improving certain metabolic markers, such as insulin sensitivity.
  • Animal studies (e.g., Plovier et al., 2017) have also shown that pasteurized Akk bacteria significantly improve metabolic health, with effects not even inferior to those of live bacteria.

Risks

  • Lower risk: The safety profile is high because inactivated bacteria cannot colonize the gut or cause infection. No serious adverse reactions were reported in the study and it was well tolerated.

Mechanisms

  • Immune regulation: Regulates immune responses primarily through the interaction of bacterial structural components (e.g., outer membrane protein Amuc_1100) with host immune receptors (e.g., TLR2).
  • Improvement of the intestinal barrier: These ingredients enhance the integrity of the intestinal mucus layer and indirectly improve metabolic health.

Live bacteria (live Akk bacteria)

Benefit

  • Improved metabolic health: Live bacteria improve metabolic disorders, enhance intestinal barrier function and reduce inflammation.
  • Regulates intestinal ecology: Produces beneficial substances through metabolic activity and interacts with other gut microbes.

Scientific basis

  • Animal studies have shown that live Akk bacteria improve metabolic status, enhance the gut barrier and reduce inflammation levels in obese mice.
  • There are fewer human studies, but preliminary evidence suggests a similar potential, although the effect may not be as dramatic as in pasteurized forms.

Risks

  • Theoretical risk: In immunocompromised populations, there may be a risk of overgrowth or triggering adverse reactions from live bacteria, but there is no evidence that Akk bacterial supplementation is harmful and is generally considered safe.

Mechanisms

  • Mucin degradation: Live bacteria degrade intestinal mucin, stimulate new mucus production and strengthen the intestinal barrier.
  • Short-chain fatty acids (SCFAs) production: Produces metabolites such as acetic acid and propionic acid, which have anti-inflammatory properties and provide energy to intestinal cells.
  • Immune regulation: Interacts directly with host immune cells to modulate the immune response.
  • Microbiota regulation: Promote a healthy microbial ecology through dynamic interactions with other gut flora.

Summarize and compare

Inactivated bacteria (pasteurized Akk bacteria)

  • Advantages: Based on existing research, it is more effective in improving metabolic health and less risky due to its inability to reproduce. Pasteurization also makes it more stable and easier to produce and store.
  • Applicable Scenarios: Ideal for supplemental needs that seek security and stability.

Live bacteria (live Akk bacteria)

  • Advantages: May provide additional benefits through metabolic activity and dynamic regulation, especially in intestinal ecological regulation.
  • Applicable Scenarios: For those who can tolerate live bacteria and want the full range of benefits.

current state of science

Current evidence slightly favors the advantage of pasteurized Akk bacteria in metabolic improvement, but live bacteria also have their own unique role. More research is still needed to validate the long-term effects and optimal application of both.

In summary, the choice of inactivated or live bacteria depends on specific needs: if safety and metabolic improvement are important, pasteurized Akk bacteria may be preferable.

Why Amcu_1100 content is the most important indicator for judging inactivated bacterial AKK products

The level of Amuc_1100 is considered the most important indicator when judging inactivated bacterial AKK (Akkermansia muciniphila) products for several key reasons:

1. Amuc_1100 is the key active ingredient

Amuc_1100 is an outer membrane protein of AKK bacteria that plays a central role in inactivating the bacteria. It has been shown that Amuc_1100 is able to interact with host immune receptors (e.g. TLR2) to modulate the immune response. This action can:

  • Improved metabolic health, such as increased insulin sensitivity and lower cholesterol levels;
  • Enhances intestinal barrier function and protects intestinal health.

For example, the study by Depommier et al. (2019) found that the effect of pasteurized AKK bacteria (i.e., inactivated bacteria) in improving metabolic parameters was strongly correlated with the presence of Amuc_1100, which underscores its importance.

2. Dependence of inactivating bacteria on structural components

Unlike live bacteria, inactivated bacteria are unable to colonize or produce metabolites in the intestinal tract, so their benefits are largely dependent on the structural components of the bacterium itself, of which Amuc_1100 is the most critical part. Key features include:

  • Stability: Amuc_1100 is able to remain stable and not easily degraded during the inactivation process, which ensures the activity of the product during production, storage and use.
  • Direct effect: Since inactivated bacteria are unable to dynamically regulate the intestinal environment, Amuc_1100 becomes the main material basis for its efficacy.

3. Scientific evidence supporting the efficacy of Amuc_1100

Several studies have provided a rationale for the importance of Amuc_1100:

  • Animal experiments (Plovier et al., 2017) showed that purified Amuc_1100 protein was able to mimic some of the benefits of inactivating AKK bacteria, demonstrating that it is the key active ingredient.
  • Human studies have shown that inactivated AKK bacteria are even more effective than live bacteria in improving metabolic health, further emphasizing the role of Amuc_1100.

4. Content directly determines product effectiveness

The level of Amuc_1100 directly affects the efficacy of inactivated bacteria products:

  • Dose effect: The higher the content, the greater the product's potential to modulate immune response, improve metabolic health and strengthen the intestinal barrier.
  • Quality assessment: Therefore, the content of Amuc_1100 has become a central criterion for the quality and effectiveness of inactivated AKK bacterial products.

Amuc_1100 is regarded as the most important indicator for judging inactivated AKK bacteria products because it is the key ingredient for the benefits of inactivated bacteria, is stable and well supported by scientific research. At the same time, its content directly determines the effectiveness of the product. When evaluating an inactivated AKK bacterial product, focusing on the amount of Amuc_1100 most accurately reflects its potential health benefits.

Why is the P9 protein the most important indicator when choosing a live Akk bacteria product? What are the risks of live bacteria products?

I. Core role and mechanism of P9 protein

1. Activation of the GLP-1 signaling pathway to regulate metabolism
  • Role of GLP-1: Glucagon-like peptide-1 (GLP-1) is a hormone secreted by the intestines that suppresses appetite, promotes insulin secretion, and inhibits fat synthesis, making it a key target for glycemic control and weight loss.
  • Role of the P9 protein: The P9 protein binds to the surface of intestinal cells through theICAM-2 receptor, triggering calcium signaling and activating GLP-1 secretion (requires IL-6 assistance). The P9 protein was shown to stimulate GLP-1 much more effectively than other proteins of Akk bacteria (e.g., Amuc_1100), and was the central driver of metabolic improvement.
2. Activates brown adipose tissue (BAT) to promote fat burning
  • P9 protein activates AMPK through the GLP-1 signaling pathway and promotes the expression of UCP1 protein in brown adipose tissue (BAT), which converts energy from white fat into calories for consumption (thermogenesis). Supplementation of high-fat diet mice with Akk bacteria resulted in a significant increase in temperature and heat production in interscapular BAT and a decrease in white fat.
3. Live bacteria dependence
  • It is the live bacteria that continue to secrete the P9 protein: Only surviving Akk bacteria can consistently produce P9 protein in the gut, while inactivated (dead) bacteria may have inadequate or inactivated P9 protein release due to cell wall rupture. The study showed that GLP-1 secretion and BAT thermogenesis were significantly better in the live bacteria group than in the dead bacteria group.

II, P9 protein is a key indicator to distinguish the effect of the product

1. Comparison with other proteins
  • Amuc_1100 protein: Amuc_1100 is another key protein of Akk bacteria, whose main function is to repair the intestinal mucus barrier and inhibit inflammation, but its contribution to metabolic regulation (e.g., GLP-1 secretion) is much weaker than that of the P9 protein.
  • Limitations of dead bacteria: Although dead bacteria retain some of their functions (e.g., inhibition of DPP4 activity, reduction of inflammatory markers), their P9 protein activity may be impaired, leading to reduced metabolic regulation.
2. Direct correlation between product effect and P9 protein content
  • The dose of P9 protein is positively correlated with GLP-1 secretion, and low doses can significantly improve metabolic markers. When choosing a live bacterial product, it is important to ensure that the strain is able to consistently secrete sufficient amounts of P9 protein.

III. Potential risks of live bacterial products

1. The issue of viable bacteria
  • 运输与储存风险: Live bacteria are sensitive to temperature and humidity, and improper production, transportation, or storage (e.g., not cold-chained) may result in the death of the strain and the inability to secrete the P9 protein.Need to choose products in capsule form (barrier to water oxygen and >=10 billion viable bacteria count), to ensure successful gut colonization.
2. Immune response and allergy risk
  • Possible immune rejection in a small number of people: Some individuals may have an intestinal environment that is not suitable for Akk bacteria to colonize, or may have an allergic reaction (e.g., diarrhea, bloating) to the P9 protein.
  • Immunodeficient persons should be cautious: Live bacteria may over-proliferate in immunocompromised individuals; medical advice is required.
3. Risk of overdose
  • Imbalance of intestinal flora: Excessive supplementation with Akk bacteria may inhibit the growth of other beneficial bacteria (e.g., Bifidobacteria, Lactobacilli), leading to a decrease in flora diversity.
  • Potential side effect: Some studies have pointed out that long-term high-dose intake may triggerBowel spasms or indigestion(further clinical validation required).
4. Controversy over the efficacy of dead versus live bacteria
  • Dead bacteria may be preferable: Inactivation of Akk bacteria (dead bacteria) is more effective in inhibiting DPP4 activity, reducing inflammation levels, and is not dependent on intestinal survival.
  • Selection Recommendations：
    • If the goal is glycemic control, weight loss or metabolic activation, prioritize live bacteria (need to ensure P9 protein activity).
    • If the goal is anti-inflammatory or repairing the gut barrier, dead bacteria may be more appropriate.

Scientific Advice on Selecting Live Bacteria Products

  1. Clearly labeled P9 protein content: Select products that state the concentration of P9 protein or are assayed by metabolic activity (e.g., GLP-1 secretion capacity).
  2. Number of live bacteria ≥10 billion/dose: Ensure that the number of live bacteria is sufficient to colonize the intestinal tract and that the activity of the strain is certified by third-party testing.
  3. Dosage form selection capsules: Avoid powder or liquid dosage forms to prevent inactivation of live bacteria by exposure to air and moisture.
  4. With Probiotics: Choose products containing prebiotics such as inulin and oligofructose to promote Akk bacteria proliferation and P9 protein secretion.
  5. Attention to storage conditions: Refrigerate or keep away from light to avoid high temperature environment to destroy the activity of live bacteria.
Scientific Advice on Selecting Live Bacteria Products
Scientific Advice on Selecting Live Bacteria Products

P9 protein is the core indicator of the effect of Akk Mushroom live bacterial products, and its activity directly determines the strength of metabolic regulation (e.g. GLP-1 secretion, fat burning). However, the risks of live bacterial products include survival rate, immune response and overdose, which need to be avoided through scientific selection and standardized use. By prioritizing the P9 protein and live bacterial activity indicators in relation to your needs (glycemic control, anti-inflammatory or fat burning), you can maximize the benefits of your product.