The probiotic industry has achieved innovative development in cross-border integration

Reporter Wang Wei

In recent years, China's probiotic industry has continuously emerged high-level academic research results, and innovative technologies have emerged one after another, continuously injecting new scientific impetus
into the development of China's probiotic industry.
What are the technical reserves of probiotic technology and industrial innovation in China, and where is its future strength? On December 23, the "2022 Probiotic Technology and Industry Innovation Forum" hosted by the Chinese Society of Food Science and Technology and supported by Yili Group was held
online.
Experts and scholars and enterprise representatives from Zhejiang University, University of Shanghai for Science and Technology, China Food Fermentation Industry Research Institute, Tenth People's Hospital Affiliated to Tongji University, China Agricultural University, Tsinghua University, Beijing Dongfanghong Aerospace Biotechnology Co.
, Ltd.
, Yili Group and other scientific and technological circles and industry conducted in-depth exchanges to explore the innovation and development of
probiotic industry.
The forum was co-chaired
by Professor He Guoqing, School of Biosystems Engineering and Food Science, Zhejiang University, and Yao Su, Vice President of China Food Fermentation Industry Research Institute.

China's probiotic industry presents three major characteristics

With the gradual deepening of scientific research on intestinal flora and the further amplification of public demand for probiotics under the background of the new crown epidemic, the global probiotics market is booming
.
From the perspective of regional market conditions, the consumption scale of probiotics in the Asia-Pacific region accounts for a high
global scale.
Shao Wei, executive vice president of the Chinese Society of Food Science and Technology, said in her speech that the probiotic industry, as a typical representative of China's emerging industry, is an important focus
for China's food industry to cultivate new momentum for development and promote the construction of a healthy China.

Shao Wei said that after more than 20 years of development, the probiotic industry has become quite large-scale, showing three major characteristics: First, many technical bottlenecks of probiotics have been solved one by one under the joint efforts of universities and enterprises, while ensuring the safety and stability of China's probiotic supply chain, it has gone abroad and gone to the world
.
Second, under the background of the healthy upgrading of the food industry, the docking and integration of probiotics and the food industry is at the best time, and the application categories tend to diversify, gradually extending from dairy products to fruit and vegetable products, snack foods and other product categories
.
Third, China's probiotic standard regulations and regulatory system are basically synchronized with the world, and the strain standard system has been continuously improved, which meets the basic needs
of the development of the industry.

Shao Wei pointed out that from the vivid practice of innovation and development of China's probiotic industry, we can more clearly understand that the foundation of the healthy development of the industry lies in innovation leadership and technological empowerment
.
The exploration and evaluation of the efficacy of probiotics is a rigorous and scientific long-term process, which is not achieved overnight, and it is necessary to pay attention to the scientific and technological investment in strains and continuously improve the scientific and technological connotation
of products.
At present, China has established a huge patent culture bank, and more and more excellent domestic strains are transformed and applied and produce good economic and social benefits
.
From the current point of view, China's probiotic market has entered the stage of value return, and consumers' purchasing behavior is more rational
.
Based on this, the probiotic industry should pay more attention to the confirmation of the quantity-effect relationship of probiotic-related products, pay attention to the whole life cycle of products, and let more high-quality probiotic products help consumers' health
.
Shao Wei also reminded that thanks to the good consumer education in the early stage of the probiotic industry, China's consumers have a high level of awareness of probiotics, but science popularization is a long-term systematic work, the industry should be highly self-disciplined in marketing and promoting products, less "exaggerated publicity", more "rigorous and professional", while increasing investment in science popularization, and jointly create a good atmosphere for industry development
.

Dr.
Yun Zhanyou, assistant to the president of Yili Group, said in his speech that Yili Group has always adhered to the road of independent innovation and research and development of probiotics, and has successively traveled to Xinjiang, Tibet, Hebei and other provinces to collect various samples such as traditional fermented foods, breast milk, infant feces, etc.
, and continue to isolate and screen new strains
.
Yili has cooperated with many domestic universities and scientific research institutions to develop a series of probiotics represented by Bifidobacterium lactis BL-99, and the strains developed have obtained a total of 15 authorized invention patents and applied to a variety of
products.
Over the years, Yili has been committed to promoting the high-quality development
of domestic probiotics.
Continuously strengthen the probiotic expert ecosystem system, support cross-field and interdisciplinary talents and scientific research team cooperation, strengthen basic innovation strength, and produce independent innovation results; Pay attention to the standardization of probiotic applications, and the research of probiotics should be developed based on the level of strains, and standardize the application and transformation of probiotics at the product end; Fully link all walks of life in industry, academia and research to carry out scientific popularization of probiotics
.
Yun Zhan You said that in the next step, Yili will strengthen the brand building of probiotics, attach importance to brand value, and deliver diversified scientific achievements to consumers in a simple and easy-to-understand form, so as to continuously meet the growing health needs
of consumers.

High-quality probiotics should be precisely developed

Professor Hao Yanling from the Institute of Nutrition and Health of China Agricultural University gave a report
on "Precise Development and Application of High-quality Probiotics".
Hao Yanling believes that the precise development of high-quality probiotics must be accurate to the strain level, because different strains come from different ecology, after long-term adaptation to the environment and evolution, resulting in gene loss and mutation
on the genome.
The second is to have a precise environment, even if the same strain is cultured in different environments, its probiotic characteristics will be different due to different
gene expression.
Genetic mutations and rearrangements
can occur when strains are domesticated under different conditions in the laboratory.

So, how do probiotics exert their probiotic properties? Hao Yanling introduced that according to the current research results, when the human body ingests probiotics, probiotics will produce some bacteriostatic substances, for example, lactic acid and bacteriocins can inhibit the growth of
pathogenic bacteria.
Lactic acid bacteria can also inhibit the growth and reproduction
of intestinal pathogenic microorganisms by colonizing the intestine.
Some probiotics not only stimulate intestinal epithelial cells and secrete mucus, but also strengthen the structure of tight junction proteins, thereby improving intestinal barrier function and thereby relieving inflammation
.
Studies in recent years have found that some probiotics can produce neurotransmitters, and some probiotics can stimulate intestinal epithelial cells, which affect the human nervous system
by affecting the gut-brain axis.

Research on probiotics is ultimately about industrialization
.
Dr.
Hong Weizhong, Director of Probiotics Research Center of Yili Group Innovation Center, introduced the application and innovation transformation
of patented strains.
Hong Weizheng said that Yili has long been committed to carrying out local research on probiotics, and has built four probiotic R&D platforms based on strain screening, functional evaluation, bacterial powder research and development and industrial transformation, and will take strains derived from Chinese breast milk and infants as the core, and is committed to the development and application transformation
of local good bacteria.
Bifidobacterium lactis BL-99 is the first self-developed patented strain
launched by Yili.
At present, Yili's independent intellectual property strains have been widely used in low-temperature fermented milk, cheese sticks, ice cream, solid drinks and other products
.

Focus on the study of intestinal microecology in different populations

Maintaining the balance of intestinal microbiome is of great significance
to the health of the elderly.
Han Ting, Director of the Department of Clinical Nutrition, Tenth People's Hospital Affiliated to Tongji University, gave a report
on "Intestinal Microecology and Elderly Health".
She believes that the abundance and diversity of intestinal flora in long-lived people are in a state of obvious advantage
.
The intestinal microecology is closely related to senile constipation and Alzheimer's disease, and the treatment effect of microecological regulation is remarkable
.
Han Ting analyzed that the reason why the elderly population is prone to intestinal microbioecology is aging, which is an age-related physiological change
.
The second is improper diet, such as a high-fat diet and a low-fiber diet
.
The third is a bad lifestyle, such as sedentary, not exercising, smoking and
drinking.
"The role of intestinal microbiome in intervening in chronic diseases has far exceeded traditional understanding
.
" Han Ting pointed out that the elderly population is in a state of chronic inflammation during the aging process, and the result of the imbalance of intestinal flora causes an imbalance in intestinal immune regulation, which in turn causes inflammation
.
In the intestines of the elderly population, Clostridium soft, which has an anti-inflammatory effect, decreases, while pro-inflammatory bacteria increase
.
Intervention by modulating the intestinal flora can reduce inflammatory aging, improve immune function, and reduce the risk of
cancer in the elderly.

Early in life is a critical period for determining the value of the intestinal flora, and during this period, breast milk is the most critical factor
in the change of intestinal flora in infants aged 0-14 months.
Zhao Ai, Assistant Professor of Vanke School of Public Health and Health, Tsinghua University, introduced the research progress
of breast milk microecology and infant health.
Zhao Ai pointed out that when human milk research is carried out now, breast milk has long been treated not as just a food source, but as a system
.
Breast milk is a microbiome, a superfood
that boosts the baby's gut flora.
Breast milk not only contains antibacterial ingredients such as lactoferrin, but also contains more than 200 kinds of human milk oligosaccharides and more than 700 kinds of bacteria
.
In the mother-infant pairing study, it was found that the breast milk flora has a direct effect
on the infant's intestinal flora.
Breast milk HMOs have a direct impact on the intestinal flora, and HMOs prevent pathogens from adhering
to intestinal mucosal cells.
Human milk fatty acids also have a direct impact
on the gut target probiotics.

Zhao Ai suggested that human milk should be studied as an ecosystem, and the nutrition and health of human milk should be included in the study of breast milk microecology, and the relationship between the combined effect of components and breast milk microecology should be deeply studied
.

Open up new cross-border perspectives for probiotic research

Spatial mutagenesis technology combines space technology with modern biological technology, and has become an important biotechnological means with Chinese characteristics, which is currently mainly used in microbial medicine and the cultivation
of new plant varieties.
So, can spatial mutagenesis be used to improve strains? "Spatial mutagenesis is not mysterious, it is actually an extension of
conventional physical mutagenesis.
However, because of the particularity of the space environment, it still has some special advantages
in research.
Strains
can be modified using spatial mutagenesis.
Pang Xin, executive vice president of Beijing Dongfanghong Aerospace Biotechnology Co.
, Ltd.
, pointed out in the report "Space Technology and Culture Research and Development: Opportunities and Challenges" that there are two main mutation factors in the space environment: radiation and microgravity
.
The space environment leads to DNA mutations in biological materials, which in turn cause metabolic and morphological changes
in organisms.
A number of strains
have been studied using spatial mutagenesis.
For example, after spatial mutagenesis of Aspergillus purpure, the growth of the strain becomes significantly faster
.
Another example is Chizhi, compared with the initial strain, the mutagenic strain hyphae is denser, neat, and grows fast
.

Pang Xin pointed out that in the future, the key problems to be solved mainly include: clarifying the safety evaluation methods of spatial mutagenic strains, especially food-grade strains, to ensure food safety; Clarify the mutagenesis mechanism and improve the mutagenesis efficiency; Prevent the degradation of mutagenic strains and improve production efficiency
.

Professor Ai Lianzhong, Dean of the School of Health Sciences and Engineering, University of Shanghai for Science and Technology, introduced the research progress
of probiotic bioengineering technology.
Elian pointed out that to analyze the mechanism of action of probiotics, good gene editing tools are an important prerequisite.

Traditional gene editing takes a long time, has many steps, and has low gene editing efficiency, so it is necessary to build a probiotic efficient gene editing system
.
At present, the CRISPR-Cas9 system
of Lactobacillus plantarum strainum, Lactobacillus casei, Streptococcus thermophilus and other strains has been constructed.
The research shows that the application of CRISPR system realizes the same-frame deletion and insertion of single genes, the continuous knockout of genes and the weakening and expression of multiple genes, and improves the editing efficiency, which solves the shortcomings
of traditional gene editing methods that take a long time and complex operation.
In terms of the study of heterologous expression of functional active ingredients by probiotics, Ailian Zhong introduced the heterogeneous production of lycopene by lactic acid bacteria as an example
.
He said that lycopene is a carotenoid C40 terpenoid, which has strong antioxidant and immune improvement effects, and has been widely used in food and cosmetics industries
.
Lactic acid bacteria cannot synthesize lycopene by themselves, but there is a pathway
for synthesizing the terpene precursor MVA.
In the study, by reconstructing the lycopene synthesis pathway, the yield of lycopene in GZQ12 reached 1.
448 mg/L after optimization, which was 20%
higher than that before optimization.
Ai Lianzhong said that the function of probiotics can also be extended to engineered probiotics, such as strengthening the function of probiotics through the optimization and regulation of functional genes
.
In addition, engineered probiotic delivery CRISPR-Cas systems can be used to achieve precise programming
of gut microbes.

At the forum, the organizer also set up a roundtable dialogue session, where a number of experts and scholars from food, public health, aerospace breeding and other fields shared their views and views
on the theme of "The Road to Innovation and Modernization of Probiotic Industry in the New Stage".
Professor He Guoqing of Zhejiang University concluded that the 21st century is the century of bioeconomy, probiotic industry as a typical representative of biological industry, from rebirth to transformation, the market scale continues to increase rapidly, the variety of strains continues to increase, the application field is more extensive, the probiotic industry system has initially formed, a large number of excellent experts and entrepreneurs have become an important force
for the innovation and development of the industry.
Looking forward to the new stage, opportunities and challenges coexist, and it is hoped that the probiotic industry will continue to gather the power of science and technology to move forward tenaciously, firmly grasp the fate of development and progress in its own hands, anchor the goal of modernization of the probiotic industry, and continue to move
forward rain or shine.

The forum aroused widespread attention and participation in the industry, and many media such as Xinhua News Agency, Guangming Net, Baidu, and Cloud Live broadcast
the meeting.
By the end of the conference, the cumulative number of views on the whole network reached 1.
178 million
.

Preliminary review: Li Song Responsible editor: Xiao Zhihan Review: Ouyang Meihua