Feed Regulation 3.0 | A New Approach to Gut Health System Control in the Antibiotic-Free Era

Starting from November 2015, the Party Central Committee and the State Council proposed to promote the livestock industry. "Environmental Protection, Health, Safety, and Efficiency" Development to meet the growing aspirations of the people for “ Healthy, safe, delicious “The demand for livestock and poultry products, the halt in 2020 by feed manufacturers of commercial feed containing growth-promoting drug additives, and, more recently, the gradual phasing out of certain antibiotics—all of these signals clearly indicate that the antibiotic-free era is upon us.”

(1) Addressing health issues should start at the root cause.

1. The goal of intensive production demands efficiency—specifically, rapid growth. But how can animals grow quickly? Simply by eating more! However, the current situation is twofold: first, insufficient feed intake leads to slow growth; second, excessive feeding overwhelms the gastrointestinal tract, hindering proper digestion and absorption, which in turn causes nutrient overload in the hindgut. This promotes microbial overgrowth in the hindgut, disrupts intestinal function, weakens the body’s immune system, and ultimately results in frequent outbreaks of disease.

2. Health stems from balanced nutrition, and the body’s ability to fully absorb nutrients depends on the digestive functions of the gastrointestinal tract. The digestive tract is an open pathway, connected at both ends to the external environment, making it highly susceptible to various types of stimuli. During digestion, numerous pathogenic factors often enter the digestive system along with feed—some of which can directly damage the gastrointestinal tract itself, while others may even penetrate deeper into the body, triggering systemic diseases. Thus, the gastrointestinal tract serves as the first line of defense for swine health, making digestive tract wellness absolutely critical.

3. To address health issues, we should tackle them at the root—starting with digestive tract health and gaining a deeper understanding of animal digestive physiology.

(II) Feeding—Digestion and Absorption Physiological Processes

1. Feeding is a fundamental activity upon which all animals depend for survival, serving as the primary step in the digestion and absorption of nutrients. Not only does feeding provide animals with sufficient nutrients to sustain vital functions and productive performance, but the act of eating also serves as a direct indicator of their health status.

2. Feeding behavior is regulated by the feeding center and the satiety center, located respectively in the lateral hypothalamus and the ventromedial hypothalamus. These two centers control the initiation and termination of eating. The hypothalamus serves as the primary central hub for regulating food intake, with short-term feeding regulation transmitted to the central nervous system via four distinct pathways. After eating, nutrients entering the stomach and the proximal duodenum activate corresponding mechanical and chemical receptors, sending signals back to the central nervous system via the vagus nerve. Additionally, certain nutrients—such as glucose—can directly influence relevant neurons in the brain to modulate appetite. Furthermore, nutrients also travel through humoral pathways to stimulate cells in the distal small intestine, promoting the secretion of glucagon-like peptide-1 (GLP-1). This hormone, in turn, suppresses gastrointestinal secretions and motility, delays gastric emptying, and ultimately inhibits food intake in animals.

3. Once feeding begins, food travels through the mouth and pharynx into the stomach—the first major site of digestion. Gastric juice is a colorless, transparent, acidic liquid composed of water, organic compounds, inorganic salts, and hydrochloric acid. Among these, the organic components primarily include digestive enzymes such as pepsin, gastric lipase, and rennin. Notably, pepsin is the most crucial enzyme, initially secreted as pepsinogen, which remains inactive until activated by hydrochloric acid. In pigs, about 10% of the hydrochloric acid secreted by gastric gland cells combines with organic substances in the mucus, forming "bound hydrochloric acid," while the remaining 90% exists in free form, known as "free acid." Interestingly, newborn piglets contain virtually no free hydrochloric acid—or very little of it—only developing trace amounts around 20 days of age. It isn’t until about 30 days old that the piglets’ gastric acid starts to exhibit mild antibacterial activity. However, even at this stage, the acidity level remains relatively low. By 60 to 75 days of age, the piglets’ gastric acid finally reaches levels comparable to those of adult pigs. Considering the inherent physiological challenge of insufficient hydrochloric acid production in piglets is therefore a critical issue that demands our attention.

4. After food is digested in the stomach, it transforms into a fluid or semi-fluid, acidic chyme that gradually moves into the small intestine, where digestion continues in the alkaline environment of the small intestine. It is here that most of the feed’s nutrients are broken down into forms that can be absorbed and utilized by the body. The small intestine produces three key digestive fluids: pancreatic juice, bile, and intestinal juice. Proteins are initially hydrolyzed into peptides and peptones under the action of gastric hydrochloric acid and proteases, then further broken down by pancreatic trypsin into polypeptides—and eventually into absorbable amino acids. Meanwhile, fats are emulsified by bile, enabling their subsequent hydrolysis into glycerol and fatty acids.

5. The large intestine contains very few enzymes. By the time chyme reaches the large intestine, most of the nutrients have already been digested and absorbed in the small intestine. What remains in the large intestine is primarily composed of substances that are difficult to break down—mainly cellulose from plant-based feed, insoluble proteins, trace amounts of fat, and digestive tract secretions. Additionally, some of the cellulose and other carbohydrates in the feed are fermented by bacteria and other microorganisms, producing low-grade short-chain fatty acids such as lactic acid, acetic acid, and propionic acid. These beneficial compounds can then be absorbed by the large intestine’s mucosal lining, making them available for the pig’s body to utilize. Moreover, over 130 types of vitamins essential for the body aren’t naturally present in food—they must be synthesized by beneficial bacteria residing in the gut. A diverse and stable microbial community thrives within the intestines, with the total weight of these gut microbes ranging from 1 to 3 kilograms per gram of intestinal contents. On average, each gram of gut content harbors approximately 1 trillion live bacteria!

6. At the very moment a new life is born and leaves the mother’s body, it contains virtually no or very few microorganisms. Once outside the maternal environment and exposed to various surroundings, the baby begins to establish its own gut microbiome. The gut microbiome plays an exceptionally vital role in sustaining life—so much so that, when compared to the human genome, it actually constitutes a significant part of an individual’s biological makeup. While the human genome consists of 24 pairs of chromosomes, the genetic diversity of the gut microbiome may outnumber an individual’s own genes by hundreds or even thousands of times.

7. Intestinal microorganisms have evolved over eons into an exquisite mechanism—through mutual cooperation with tens of thousands of microbes, we’ve become a fully integrated, symbiotic organism. When the composition and metabolism of gut microbiota remain in dynamic equilibrium, influenced by environmental factors and nutrition; however, if this delicate balance is disrupted, animals will begin to experience health issues.

8. As for the gut, it possesses its own defense mechanisms. The normal microbiota residing on the intestinal mucosa forms the gut's biological barrier, while certain chemical substances secreted by the intestinal epithelium create a chemical barrier structure that inhibits and even kills pathogenic microorganisms. Meanwhile, the mechanical barrier of the gut is primarily composed of intestinal epithelial cells, the underlying lamina propria beneath the epithelium, and the tight junctions between adjacent epithelial cells. The gut is one of the largest immune organs in animals. Based on its function and distribution, the intestinal mucosal immune system can be divided into Gut-Associated Lymphoid Tissue (GALT) and diffuse immune cells. Among these, Gut-Associated Lymphoid Tissue mainly refers to the aggregated lymphoid follicles—specifically, Peyer’s patches—distributed throughout the intestine, serving as the primary sites for initiating and activating immune responses. In contrast, diffuse immune cells act as the effector components of intestinal mucosal immunity.

Summary ： 1. Digestive tract health is crucial; 2. All antibiotic-free and alternative-antibiotic product research should align with the animals' natural physiological processes.

(1)    Feed Intake Regulation 1.0, Feed Intake Regulation 2.0

Now, let’s share our research and insights. As we just discussed, animal health essentially revolves around addressing the key link: "feed intake—digestion & absorption—gut health—immunity enhancement." If we simplify this chain further, it ultimately comes down to one fundamental issue: how animals eat. Specifically, how they can consume more feed efficiently, maximizing nutrient conversion—and, most importantly, how eating wisely leads to optimal health. For the past 27 years, Dadi has been deeply immersed in research along this very same line, focusing relentlessly on precisely controlling animal feed intake. Our range of flavoring products goes beyond simply appealing to animals’ senses; they actively stimulate digestive juice secretion, boost digestive enzyme activity, and enhance overall digestion, thereby significantly improving feed consumption. Currently, we’re advancing into Feed Intake Regulation 3.0—a new era that builds upon the earlier stages of Feed Intake Regulation 1.0 and 2.0. In this phase, our primary focus remains on boosting feed intake while simultaneously optimizing digestive processes in animals. Back when we started, we leveraged animals’ natural olfactory and gustatory abilities to identify the flavors pigs find most irresistible. Later, grounded in the imprinting effect theory, we developed groundbreaking mother-child integration technology for our flavoring agents. More recently, we’ve even explored substances capable of blocking hormones that inhibit feed intake regulation, aiming to enhance feeding behavior from a physiological standpoint. Additionally, inspired by pigs’ innate preference for proteins and amino acids, we’ve pioneered innovative amino acid-based flavoring technologies to create highly effective products. Of course, we’re far from resting on these achievements. On the contrary, there are always fresh challenges waiting for us to tackle—and we’re eager to push the boundaries of what’s possible in this exciting field.

(II) Feed Intake Regulation 3.0

In this section, let me highlight our research on acidifiers and plant essential oils.

Acidifier Research

As we just mentioned, newborn piglets do not produce free hydrochloric acid, and by 30 days of age, the gastric juice in pigs contains very little inhibitory capacity against bacteria due to its low levels of free hydrochloric acid. Given these inherent physiological challenges in young animals, acidifiers have long been recognized as an effective solution to address insufficient gastric acid secretion in early-stage piglets. But how can we tackle this issue? Specifically, we’ve considered three key questions: How can we develop acidifiers that are highly palatable to pigs? How can we ensure that the acid releases more hydrogen ions for optimal effectiveness? And finally, how can we maximize the acid’s benefits in the intestinal tract? It’s precisely from these considerations that our third-generation acidifier product was born.

1. From a taste perspective, pigs show a moderate preference for acidity. Initially, pig pharyngeal neurons perceive acidic stimuli as painful—only after adapting over time do they begin to register it more neutrally. In our earlier experiments with acidifiers, we observed positive effects such as improved weight gain and reduced diarrhea, yet sometimes feed intake was lower. This could very well be due to the palatability of the acidifier itself, a factor that is often overlooked. Therefore, while ensuring the functional efficacy of acidifiers, enhancing their palatability remains a crucial issue that product developers must carefully consider.

2. Our second consideration regarding acidifiers is how to ensure the release of more hydrogen ions, since pH is closely linked to pepsin activity. Pepsin functions optimally at a pH range of 2.0 to 3.5. We’ve reviewed all acidifier products available on the market, and found that most of them fall within this ideal pH range. Among these, nearly 50% have a total acidity level between 60% and 70%, yet only about 5% of that total acidity actually contributes meaningfully to pepsin activity—while the effective total acidity could reach as high as 30%.

3. What is effective total acid? We believe that an acid capable of releasing more hydrogen ions at a pH of 3.5 can be considered "effective total acid." In fact, we are the first to introduce this concept of effective total acid. We collected several commonly available products on the market and measured their effective total acidity—only two products met our criterion, achieving an effective total acid level of 30%. But does this align with our hypothesis that effective total acid is positively correlated with pepsin activity? To verify this, we conducted a series of experiments, and the results confirmed that our hypothesis holds true. It’s precisely this innovative research approach that inspired the development of our Acid Infinity product line.

4. Our third consideration regarding acidifiers: how to optimize raw materials and refine processing techniques to maximize their effectiveness in the intestinal tract. To meet this goal, we must first screen various acidic ingredients, selecting those that can release more hydrogen ions. We’ll then choose the acids with the best antibacterial performance and optimize the ingredient combination based on criteria that broaden the spectrum of inhibition. Additionally, we’ll specially treat acids with slightly lower palatability and coat those designed to modulate gut microbiota. Ultimately, the optimized product demonstrated superior antibacterial activity against Gram-positive bacteria compared to the antibiotic group in in vitro tests. Importantly, when conducting antibacterial experiments, it’s crucial to evaluate results both in vitro and in vivo for a comprehensive understanding. That’s why we’ve continued our animal trials at our own experimental farm, where the outcomes have been quite promising. Yet, we’re not stopping there—what about performance under extreme conditions? To address this, we partnered with a pig farm in Qionglai, Chengdu, where diarrhea cases are particularly severe. There, we conducted a trial involving a group of piglets seven days after weaning, comparing the acidifier-treated group with the antibiotic-treated group. Preliminary data show that the acidifier performed just as well as the antibiotics in terms of reducing diarrhea incidence. We’ve also set an even higher standard: testing the product under antibiotic-free conditions immediately after weaning. Since this experiment is still ongoing—having only been completed two days ago—we’re unable to share the detailed results at this stage.

In summary, regarding the acidifier product, I’d like to highlight two key points. First, it’s crucial to address the issue of acidifier palatability—while ensuring its functionality, the product must also be highly appealing to animals. Second, when using an acidifier, always make sure to administer the correct dosage, rather than relying solely on it for a placebo effect.

Research on Plant Essential Oils

Research on essential oils was sparked by mold growth observed in a blank formulation during one of our experiments. Our company happens to have a small-scale granulation machine, which we use for granulation tests aimed at evaluating the pleasantness and longevity of fragrance compounds. Through these experiments, we noticed that the unscented blank formulations tended to mold easily every time—leading us to conclude that fragrance ingredients likely possess inherent antibacterial and antifungal properties. In fact, our fragrance ingredient catalog includes more than 1,000 different components, and several of these are essential oil-derived substances listed among our fragrance raw material options. As a result, we have an excellent understanding of the functions and unique characteristics of essential oil components.

When it comes to research on plant essential oils, we have three key considerations: First, essential oils contain a wide variety of components, so it’s crucial to thoroughly understand the raw materials. Chemically classified, essential oils can be divided into several major categories, each with its own unique functions. For instance, phenols stand out as a particularly notable group known for their potent antibacterial properties. Second, it’s important to identify the specific components responsible for genuine antibacterial activity. When selecting these active ingredients, aim to broaden the spectrum of antimicrobial effectiveness while ensuring that the minimum inhibitory concentration is achieved. Finally, although some essential oils exhibit remarkable antibacterial effects, they often suffer from extremely poor palatability—another critical factor to keep in mind when choosing which oils to use.

Much research has been conducted on the functions and mechanisms of essential oils, but currently, several challenges remain. These include addressing the issue of palatability, as well as tackling stability concerns such as their tendency to easily evaporate and oxidize.

For us, these are actually the issues we study on a daily basis. As shown in the figure, here are the advantages of our plant essential oils:

Summary: When selecting essential oils, it’s recommended to consider their stability, palatability, and antibacterial concentration. Additionally, follow the application guidelines—ensure that the right amount of essential oil is added.