China Food

From faeces to yogurt, a gold game of probiotics

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Brand, strain, efficacy and other information of probiotic products on e-commerce platform | fruit shell hard technology tabulation
probiotic wind is really blowing.
what are probiotics?
The term
probiotics was first proposed by German microbiologist Werner kollath in 1953 to describe bacterial supplements used to treat malnutrition.
with the deepening understanding of probiotics, the connotation and extension of probiotics have also been upgraded. In 2001, the food and Agriculture Organization of the United Nations and the World Health Organization clearly defined “probiotics” as “active microorganisms that produce health benefits to the host when ingested in sufficient quantities.”
from this concept, yeast, bacillus, Clostridium butyricum, lactic acid bacteria and other bacteria and fungi belong to the category of probiotics.
but another problem follows. The health care efficacy of these probiotics is very different, and the clarity of the effect is also different. The academic community also needs a standard to distinguish the clarity of the efficacy of probiotics.
therefore, in 2011, the world gastroenterology Organization released the global overview of probiotic evidence levels [1], which divided the clarity of probiotic function into four categories:
Classification of functional clarity of probiotics | hard shell technology tabulation
. Among them, lactic acid bacteria were the first to be verified for their efficacy. As the most common probiotics, lactic acid bacteria include 18 genera such as Lactobacillus, Pediococcus, Streptococcus and Bifidobacterium. They widely exist in the intestine and mouth of animals and can maintain the microecological balance of the digestive tract. Non lactic acid probiotics such as Bacillus
and Clostridium butyricum are related to people’s long-term eating habits. For example, Bacillus used to make natto has antibacterial effect and is beneficial to cardiovascular and cerebrovascular health.
in addition, Ackermann’s bacteria, Bacteroides fragilis and Clostridium vulnificus are regarded as the next generation of probiotics. At present, there is little preliminary research on them, but some evidence shows that they play an important role in regulating human immunity, metabolism and other functions. [2] Although the role of
probiotics is extensive, the specific commercialization depends on the policy.
Daye probiotics
in 2001, 2010 and 2011, the former Ministry of Health issued the list of probiotic strains that can be used in health food, the list of fungal strains that can be used in health food, the list of strains that can be used in food and the list of strains that can be used in infant food, allowing manufacturers to use 35 species and subspecies of probiotics in food. Although it has been supplemented several times, most of them are lactic acid bacteria, and a few are yeast and other bacteria and fungi.
List of edible probiotics [3] | fruit shell hard technology tabulation
that is to say, most probiotic products and companies in China also focus on the commercialization of lactic acid bacteria. It is not surprising that the commercialization of lactic acid bacteria has a long history: as early as 1930, lactic acid bacteria were made into beverages in Japan and are the “eldest son” of the whole industry.
in order to make use of probiotics other than lactic acid bacteria, some companies focus on innovative drugs, so that they can bypass the list of strains mentioned above and take the road of trial and clinical approval; In addition, some companies use probiotics in animals and plants to improve the efficiency of agricultural production.
two types of companies thus constitute three major categories downstream of the probiotic industry: consumer goods, drugs and agricultural products.
Classification of probiotic products | nut shell hard science and technology drawing
Probiotic consumer products
consumer products are the downstream products with the widest application range and the highest product proportion in the probiotic industry. This kind of probiotic products mainly focus on food and beverage, which can be further divided into the following three categories:
fermented dairy products.
fermented dairy products mainly include fermented milk and lactic acid bacteria drinks, among which yogurt everywhere is the most common fermented milk, while Yakult and Yili Meitian belong to lactic acid bacteria drinks.
they are the products with the highest share in the probiotic industry and an important source of growth for the domestic probiotic industry. According to the data of Tianfeng securities, the consumption scale of fermented dairy products in China accounted for 78.4% of the overall domestic probiotic market in 2019. Among them, the fermented milk market exceeded 80 billion yuan that year, and the lactic acid bacteria beverage also reached nearly 40 billion yuan. [4]
probiotic tonic
oral probiotic lyophilized tablets and lyophilized powder launched by pharmaceutical enterprises and health products companies belong to probiotic tonic.
if the consumption of yogurt is only to satisfy the appetite, the purchase of probiotics is more a health investment, and consumers are interested in its “health care” effect.
in China, the executive standard of probiotic supplements of various brands is GB / t29602, which belongs to solid beverage [5]. This means that these manufacturers should also abide by the list of strains that can be used in food. There are less than two kinds of strains and more than a dozen kinds of strains used in probiotic supplements on the market, but they all belong to lactic acid bacteria, mainly all kinds of Lactobacillus and Bifidobacterium.
in addition, the role of oral probiotics and gynecological probiotics has been confirmed, and probiotic products for corresponding parts have begun to appear on the market.
Oral products | hard shell technology tabulation
The 2019 Research Report of Everbright Securities shows that the global market revenue of probiotic supplements is US $42.5 billion. Among them, China has the largest market potential, which will increase from 3.5 billion yuan in 2018 to 6.1 billion yuan in 2023, with a compound annual growth rate of 12%. [6]
special foods
such probiotic products include infant formula with probiotics added. Tisai also found that Bifidobacterium was related to the frequency of diarrhea and nutrient absorption rate of infants.
Probiotic drugs
with the accumulation of clinical data, the efficacy of probiotics has become more and more clear. Innovative drugs have also become an important product branch of probiotics, while probiotic drugs can be further divided into traditional probiotics and living biological drugs.
traditional microbial preparation
has the function of regulating immunity, gastrointestinal function and controlling inflammation because of some probiotics. Therefore, microbial agents are used to fight and treat Helicobacter pylori infection, nonalcoholic fatty liver, irritable bowel syndrome and other diseases. At present, there are some domestic approved drugs such as amikacin and Bifidobacterium. Foreign medical institutions are also widely using euga lein, omniflora, synergac and other brand products.
living biological drug
around 2010, the focus of academic research on probiotics has changed.
on the one hand, scientists have found that probiotics in the gastrointestinal tract can not only help digestion and anti-inflammatory.
there are complex connections between the gastrointestinal tract and various human organs, that is, the so-called intestinal brain axis, intestinal heart axis, intestinal liver axis, intestinal lung axis and so on. Probiotics can indirectly affect the function of various systems by affecting the “intestinal-x axis”.
on the other hand, scientists began to pay attention to probiotics outside the gastrointestinal tract, and their functions were explored one by one.
gastrointestinal microorganisms account for 80% of human microorganisms, and the other 20% are distributed in the skin, oral cavity, respiratory tract and urogenital tract, maintaining the micro ecological balance of each system. It has been found that as long as the probiotics in some parts of the human body are intervened, the health status of the corresponding parts can be improved and even diseases can be treated.
At present, there are three technical routes for living biological drugs, namely fecal bacteria transplantation, multi strain living biological drugs and single strain living biological drugs. The three technical routes have their own advantages and disadvantages.
Three technical routes of living Biopharmaceutics [16] | source: warm hearted intestinal Research Institute
. Among them, fecal bacteria transplantation has a higher technical maturity and more companies. The fastest progress of
is seres therapeutics, established in 2010. The company was listed on NASDAQ in 2015, with a market value of more than $1.5 billion at one time.
in January 2022, ser-109, a microbial capsule extracted from human feces and used to treat Clostridium difficile infection, manufactured by seres therapeutics, was successful in phase III clinical trial [17]. Seres therapeutics said that it is expected to obtain FDA approval in mid-2022 and become the first approved “fecal bacteria capsule”. According to the official website of
company, in addition to ser-109, the company has five R & D pipelines at an earlier stage. [18]
finch therapeutics, a subsidiary of American fecal bank openbiome, also launched an experimental drug cp101 made from freeze-dried human feces and passed the phase II clinical trial at the end of 2021. Rebiotix, a probiotic treatment company acquired by Huiling pharmaceutical in 2018, made fecal bacteria into an enema, which completed phase III clinical trials in 2021. According to the data of
heartwarming Research Institute, VC has invested more than $1 billion in living biological drugs in the past five years and is still investing continuously. [16]
although there are similar companies in China, the commercialization progress is mostly later than that of foreign companies.
Zhiyi biological was founded in 2013. Sko8 live bacteria powder, the company’s live bacteria drug, was approved to enter the clinic in November 2019. It is the first living biological drug to enter the clinic in China, but the drug is currently in phase 2 clinical stage. [19]
unknown gentleman, founded in 2017, focuses on fecal bacteria transplantation and formula bacteria. Different from the above-mentioned American companies, unknown Jun claims to use artificial intelligence technology, which can improve the efficiency and success rate of new drug development. In December 2021, unknown gentleman completed tens of millions of dollars of round B + financing, led by Chunhua capital and ⾼ Rong capital.
in addition, Munn biology also completed the 200 million yuan round C financing led by SDIC in December 2021. Munn biology was founded in 2015, and its seven agricultural probiotic products have been listed. In addition, seven innovative fecal bacteria transplantation drugs under research and development remain before the new drug application stage. [20]
Agricultural supplies
probiotic products used in agricultural production include animal probiotics and plant probiotics. The former is generally used in animal feed to improve the intestinal flora of livestock, while the latter is used in crop planting to improve soil and fertilizer utilization.
, as an industry that has developed for nearly a century, the market scale of probiotics in the world is relatively stable, but there is considerable incremental space in China.
Tianfeng securities data show that in 2020, the global probiotic market scale exceeded 200 billion yuan, of which China’s market share exceeded 80 billion yuan. It is expected to be close to 100 billion yuan by 2022, with an average annual growth rate of about 14%. [4]
this is an obvious business opportunity.
but probiotic companies should first solve the problem of strain supply before commercialization, but those stable and easy-to-use probiotics are firmly in the hands of foreign companies.
neck stuck “bacteria chip”
the current situation of domestic probiotic industry is no better than that of seed and breeding pig industry.
at present, international probiotic patents are basically monopolized by the United States, Japan, Russia and other countries, and domestic probiotic raw materials must also be imported from these countries. According to the Research Report of Tianfeng securities, the domestic probiotic raw materials in 2020 mainly come from American company DuPont and Danish company kohansen. The raw materials supplied by the two companies account for 85% of the overall domestic market. [4]
why do probiotics get stuck? The main reason for
is that foreign countries have the leading advantage of R & D and commercialization.
Pasteur, a French microbiologist, discovered the principle of fermentation in 1865, which laid the foundation for the study of probiotics in Europe.
in 1899, Tissier, a scientist at the Pasteur Institute, discovered Bifidobacterium. Six years later, Russian microbiologist Mechnikov, who also worked at the Pasteur Institute, found a kind of lactic acid bacteria in Bulgarian yogurt. Mechnikov named it “Lactobacillus bulgaricus” and attributed it to the longevity of local people.
Mechnikov’s work inspired Hiroshi Daida, a doctor of medicine at Kyoto University in Japan. In 1930, Minoru Daida isolated a Lactobacillus casei strain that could resist gastric acid and bile and reach the intestine alive, and founded a company to sell Yakult all over the world. Until today, you can still hear the words “strengthen cultivation and reach the intestines” in the advertisements of Yakult.
China has not started relevant research in the 1970s. At that time, the Beijing milk company still used the method of “Introduction” of old yogurt to make yogurt. It was not until 1981 that the Beijing Dairy Research Institute was established to systematically study probiotics and produce lactic acid bacteria powder. [21]
the backward research time means that patents are controlled by others.
today, the three major international probiotic suppliers DuPont of the United States, kohansen of Denmark and Raman of Canada were established in 1802, 1874 and 1915 respectively. They have accumulated a large number of patents, such as Bifidobacterium Bb-12 of cohenson and Lactobacillus rhamnosus hn-001 of DuPont, with guaranteed safety and efficacy.
the application of foreign patented strains is often used as a selling point for some expensive yogurt in China.
Strains, sources and prices of some commercially available yogurt | hard shell technology tabulation
domestic research on probiotics started late, but fortunately, it developed rapidly. According to the data of “warm hearted intestinal Research Institute”, a domestic think tank in the field of intestinal tract, the number of papers published in the field of probiotics in China has increased rapidly since 2008, and surpassed the United States in 2018.
Comparison of the number of probiotic papers published between China and the United States from 2000 to 2020 source: [16] behind the growth rate of
research is the accelerated pace of probiotic industrialization.
first of all, domestic dairy enterprises changed their ideas and began to improve their R & D capabilities.
in recent years, Mengniu, Yili, new hope and other companies have begun to develop and cultivate their own patented probiotics and apply them to their own products.
Self developed strains and application of domestic dairy enterprises | fruit shell hard technology tabulation
. In addition, there are also vertical companies of probiotic raw materials in China.
in 2003, Ketuo biology was established in Beijing to produce all kinds of probiotic supplements for human, animal and plant use. It was listed on the Shenzhen Stock Exchange in July 2020.
prospectus shows that Ketuo biology has acquired several companies since 2014 to establish patent barriers. Up to the time of listing, Koto bio has mastered the strain resource library of more than 10000 strains of lactic acid bacteria, including five core probiotic strains: Lactobacillus casei LC Zhang, Bifidobacterium lactis V9, Lactobacillus plantarum p-8, Bifidobacterium lactis probio-m8 and Lactobacillus rhamnosus probio-m9. [22]
on the one hand, Ketuo biology directly launched its own brand to consumers, including the compound probiotic tonic “yishiyou” and the customized “prebiotic and beauty”. On the other hand, Ketuo biology also supplies probiotic raw materials to b-end customers. According to the official website of Ketuo biology, the company’s customers include dairy enterprises such as Mengniu and Guangming, pharmaceutical enterprises such as sunflower pharmaceutical and Jiangzhong pharmaceutical, as well as agricultural enterprises such as western animal husbandry and Northern lianniu. [23]
however, according to the 2020 annual report of Ketuo biology, the sales volume of the company in that year was RMB 284 million, of which 73.43% of the revenue came from Mengniu, which was highly bound to Mengniu and had no bargaining power [24]. A person close to Mengniu told the fruit shell hard technology team that although the price of domestic probiotics is cheaper, considering the brand effect of foreign strains, the strains of domestic dairy enterprises are still mainly imported.
domestic companies with similar business to Ketuo biology include runying biology, Weikang probiotics and Yiran biology, but they are not listed.
the lifeline of income is in the hands of major customers, and the competitiveness of products can not compare with foreign products. Is there still a chance for the probiotic industry?
New opportunities for indigenous bacteria
in the final analysis, the reason why the probiotic products of foreign giants are popular with downstream companies is nothing more than two points: superior biological characteristics and sufficient clinical verification. Domestic probiotics have been industrialized for more than 40 years. Large companies have found core strains with superior characteristics from home. The rest is to continue clinical and expand clinical practice, and use data to change consumers’ views, which can only be left to time.
but we still believe that compared with foreign companies, local probiotic companies still have irreplaceable advantages.
probiotics cultivated by foreign companies may not adapt to the intestinal conditions of Chinese people. A large number of studies in
academic circles have shown that people of different races and regions have different gastrointestinal flora structure, which is related to everyone’s dietary structure and living habits [25]. “Some probiotic strains isolated from the intestines of Chinese people will also show different characteristics from some foreign strains in genome.” Professor Wang Gang of the food College of Jiangnan University once said that probiotic products developed with local strains are more suitable for the Chinese market. [26]
Zhang Heping, Professor of Inner Mongolia Agricultural University and chief scientist of Ketuo biology, believes that China likes hot-pot/" 22375 rel="nofollow" target="_self">hot pot and barbecue, and many people have the tendency to abuse antibiotics. Therefore, it is more recommended that Chinese people take probiotic strains with strong vitality and can prevent the breeding of “bad bacteria”. [27]
the same applies to companies that transplant fecal bacteria.
in addition, foreign star probiotics are not 100% safe.
in March 2020, a study in the Journal of the American Medical Association pointed out that the regulation of the probiotic market is very chaotic. The academic research on probiotics mostly focuses on its effectiveness, but ignores the safety risk of ingesting live bacteria. [28]
previous studies have confirmed that the intake of probiotics may increase the incidence of bacteremia, allergy, eczema and other diseases.
Research on the negative effects of probiotics | fruit shell hard technology tabulation
, and LGG probiotics is a patented strain of kohansen company and one of the most studied probiotics in the world. Kangcuile, Baotian’s Probiotic tonic and Jane Eyre’s yogurt are all using this probiotic.
on February 8, 2022, a team from the University of Toronto in Canada found that lactic acid bacteria may aggravate the condition of patients with pancreatic ductal adenocarcinoma. The study was published in the cell journal immunity. [32]
this is both an opportunity and a risk for the domestic probiotic industry.
thanks to the awakening of consumers’ health awareness, the domestic probiotic industry has spent the best 20 years, but can it continue to be optimistic in the future?
you should know that the Federal Trade Commission of the United States still considers probiotic products that claim to reduce gastrointestinal discomfort, improve immune health, relieve constipation and the common cold as “deceptive advertising”, while the European food safety agency has repeatedly refused to endorse the health effects of probiotic supplements, and the reasons of both institutions are “insufficient evidence”. [33]
this may also explain the strange phenomenon in the table at the beginning of the article – when all probiotic supplements try to “put gold” on their faces, Bayer and Pfizer’s products do not promise any effect.
moderate marketing and return to science is the market that consumers like. We have seen too many health care products rise and fall in the face of scientific evidence.
I hope probiotics will not be next.
Author: Yang Jingyi; Source: nutshell hard technology (ID: guokr233), reprint has been authorized. Reprint authorization and media business cooperation: Amy (wechat: 13701559246); Foodaily Expo 2022] in line with the original intention of providing the whole value chain and one-stop industrial innovation services for the industry, foodaily Expo 2022 (2022.05.31-06.02, Shanghai) is further upgraded. In addition to the upstream and downstream of the food industry, it also covers and gathers multiple resources such as e-commerce, social media, traffic, channels and capital, aiming to bring you an annual innovation feast. Here, products, content, technology, marketing and other aspects related to food & brand innovation will be presented in the form of “professional exhibition + innovative content + interactive experience”, breaking through and differentiating in the consistent form of industry exhibition.

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