Method for preventing or treating abnormal emotions or behaviors in non-human animals using lactic acid bacteria

Abstract

The present disclosure provides a method for preventing or treating emotional or behavioral problems in non-human animals, such as fear, phobia, anxiety and aggression, by administering lactic acid bacteria to the non-human animal in need thereof.

Description

Technical Field

[0001] The present disclosure relates to methods for preventing or treating emotional and behavioral problems in animals, and more particularly to methods for preventing or treating fear, phobia, anxiety, and aggression in non-human animals.

Background Art

[0002] The health benefits of companion animals or livestock are generally widely recognized. According to surveys, pet owners tend to have fewer illnesses, recover more quickly from serious health conditions, and have a greater sense of satisfaction than those who do not own pets. Some specific potential benefits of owning a companion animal include a reduction in loneliness, an increase in compatibility with humans, a reduction in allergies, a decrease in blood pressure, and an improvement in encounters with others and social skills, all of which are strongly related to mental and physical health.

[0003] However, like humans and other animals, companion animals and livestock can also cause emotional and behavioral problems. These problems can weaken the bond between the pet and the owner and reduce the owner's dedication to caring for the pet. In fact, emotional and behavioral problems are the main reasons for surrendering, abandoning, or euthanizing pets to animal shelters or refuges. For example, a common reason for returning a dog is behavior resulting from separation anxiety. In an average veterinary practice in the United States, it is estimated that up to 14% of dog patients exhibit one or more signs of separation anxiety, such as abnormal urination or defecation, destruction, and vocalization. Other behaviors associated with anxiety may include salivation, loss of appetite, and lethargy.

[0004] Therefore, when these problems occur in companion animals or livestock, prompt attention and treatment are necessary. In companion animals, the treatment of behavioral problems varies depending on the diagnosis and prognosis. Generally, treatment programs start with the prevention and avoidance of problems and the initial modification of behavior. Initially, prevention is necessary to avoid further compromising the welfare of the pet and to ensure safety in case of aggression. At the same time, the owner needs to develop effective strategies to modify the pet's behavior and be able to gradually reintroduce the pet to the problem situation while achieving the desired results. If the pet successfully achieves its intended goal (e.g., escape from or retreat from a stimulus), the repetition of that behavior may further exacerbate the problem and condition further anxiety each time it is exposed to an unpleasant outcome. Improvement is generally a slow, step-by-step process, and environmental changes may be necessary to enable the pet to be kept away from the stimulus (or the sight or sound of the stimulus). The modification of the pet's behavior is mainly achieved by applying the principles of learning and behavior modification, together with the use of products (e.g., muzzles, head halters, no-pull harnesses, etc.) that help to improve safety, reduce anxiety, or more effectively achieve the desired response, and by achieving the desired results and providing rewards.

[0005] For some pets and some problems, drugs or natural products may also be applicable. Various natural products have been used in the treatment of anxiety neurosis, but very little evidence has been shown to support their effectiveness. Psychotropic drugs such as amitriptyline, buspirone, clomipramine, and fluoxetine are recommended as adjuvants for behavior modification in the treatment of selected cases of nuisance barking.

[0006] Therefore, there remains an unmet need to effectively prevent or treat abnormal emotions and behaviors in non-human animals. SUMMARY OF THE INVENTION

[0007] In the present disclosure, it has been found that the lactic acid bacterium Lactobacillus plantarum subsp. plantarum PS128 (hereinafter also referred to as PS128) is effective in preventing or treating abnormal emotions and behaviors, such as fear, phobia, anxiety, and aggression, in non-human animals.

[0008] In one embodiment of the present disclosure, a method for preventing or treating abnormal emotions or behaviors in non-human animals is provided. In one embodiment, the non-human animal is a companion animal, livestock, pet, agricultural animal, or pack animal. In another embodiment, the non-human animal is a dog, cat, goat, pig, sheep, cow, chicken, donkey, llama, camel, elephant, monkey, chimpanzee, gorilla, deer, duck, goose, pigeon, turkey, rabbit, squirrel, mouse, rat, hamster, guinea pig, or horse. According to the present disclosure, the method comprises administering a composition, the composition comprising an effective amount of Lactobacillus plantarum subsp. plantarum PS128, deposited under DSMZ accession number DSM28632, and a carrier. In one embodiment of the present disclosure, the composition is orally administered to the non-human animal.

[0009] In one embodiment, the effective amount of PS128 administered per kg of body weight per day is at least 1×10 7 CFU, at least 1 × 10 8 CFU, at least 1 × 10 9 CFU, at least 1 × 10 10 CFU, or at least 1 x 10 11 CFU and 1 x 10 7 CFU, 2 × 10 7 CFU, 3 × 10 7 CFU, 4 × 10 7 CFU, 5 × 10 7 CFU, 6 × 10 7 CFU, 7 × 10 7 CFU, 8 × 10 7 CFU, 9 × 10 7 CFU, 1 × 10 8 CFU, 2 × 10 8 CFU, 3 × 10 8 CFU, 4 × 10 8CFU, 5×10 8 CFU, 6×10 8 CFU, 7×10 8 CFU, 8×10 8 CFU, 9×10 8 CFU, 1×10 9 CFU, 2×10 9 CFU, 3×10 9 CFU, 4×10 9 CFU, 5×10 9 CFU, 6×10 9 CFU, 7×10 9 CFU, 8×10 9 CFU, 9×10 9 CFU, 1×10 10 CFU, 2×10 10 CFU, 3×10 10 CFU, 4×10 10 CFU, 5×10 10 CFU, 6×10 10 CFU, 7×10 10 CFU, 8×10 10 CFU, 9×10 10 CFU, 1×10 11 CFU, 2×10 11 CFU, 3×10 11 CFU, 4×10 11 CFU, 5×10 11 CFU, 6×10 11 CFU, 7×10 11 CFU, 8×10 11 CFU, and 9×10 11 including, but not limited to, CFU.

[0010] In one embodiment, the dosage of PS128 administered per kg of body weight per day is at least 0.01 g, at least 0.02 g, at least 0.03 g, at least 0.04 g, or at least 0.05 g. In another embodiment, the dosage of PS128 administered per kg of body weight per day is 0.01 g, 0.015 g, 0.02 g, 0.025 g, 0.03 g, 0.035 g, 0.04 g, 0.045 g, or 0.05 g.

[0011] In one embodiment of the present disclosure, the abnormal emotion or behavior is selected from the group consisting of fear, phobia, anxiety, and aggression. In a further embodiment, the abnormal emotion or behavior includes one of vocalization, hyperactivity, destruction, sleep abnormality, eating abnormality, drinking abnormality, grooming abnormality, excretion abnormality, socialization disorder, compulsive behavior, barking, growling, biting, mouthing, separation anxiety, play aggression, and any combination thereof.

[0012] In one embodiment of the present application, the score or value for evaluating abnormal emotion or behavior in a non-human animal is improved. In a further embodiment, the evaluation includes the evaluation of emotional and cognitive disorders in dogs (EDED) or the scoring of a dog behavior checklist.

[0013] In one embodiment of the present disclosure, after administration of the composition, the value of the evaluation of emotional and cognitive disorders in dogs (EDED value) decreases statistically significantly. In another embodiment, after administration of the composition, at least the score of the dog behavior checklist decreases statistically significantly. In yet another embodiment, after administration of the composition, the total score of the dog behavior checklist decreases statistically significantly.

Brief Description of the Drawings

[0014]

Figure 1

Figure 2

Modes for Carrying Out the Invention

[0015] The following examples are used to illustrate the present disclosure. Those skilled in the art can easily understand other advantages and effects of the present disclosure from these examples. Unless departing from the spirit of the disclosure, the present disclosure can be implemented with various modifications and changes. It is understood that the examples provided below are merely illustrative of the present disclosure and should not be regarded as limiting the scope of the present disclosure.

[0016] Fear and Phobia

[0017] Fear is a normal reaction to an actual or perceived threatening stimulus or situation. Apprehension or anxiety is a reaction to fear and excitement when an animal anticipates a threat or a scary situation. A phobia is an exaggerated fear reaction. Fear reactions may include displacement behaviors such as panting, salivation, tail tucking, ears down, staring, low posture, piloerection, vocalization, or displacement behaviors such as yawning or lip licking. Avoidance and escape are one strategy, but some dogs use aggression to remove the stimulus that induces fear, and their behavior is strengthened by the success (negative reinforcement).

[0018] More common examples include the following: 1) Fear of other dogs, especially unfamiliar dogs, dogs that appear threatening, or dogs that have had an unpleasant experience, 2) Fear of unfamiliar humans, especially novel humans, or humans with an appearance, behavior, or smell different from that of familiar people (e.g., infants), 3) Fear of inanimate stimuli, such as loud or unfamiliar sounds (e.g., construction work, trucks, gunshots, etc.), visual stimuli (e.g., umbrellas, hats, uniforms, etc.), environments (e.g., backyards, parks, pet hotels, etc.), surfaces (e.g., grass, tile or wooden floors, stairs, etc.), or combinations of stimuli (e.g., vacuum cleaners, car rides), and 4) Fear within specific situations, such as within a veterinary clinic or a grooming parlor.

[0019] A dog's fear response is generally associated with loud noises (such as thunder, fireworks, gunshots, etc.), and the stimuli related to these events include rain, thunder, and even static or pressure changes associated with thunderstorms. Some fears (such as going to the veterinary clinic, going outdoors, entering a specific room, or walking on a specific type of floor, etc.) can intensify and potentially meet the definition of a phobia.

[0020] Separation anxiety

[0021] Separation anxiety is the inability of a pet to find comfort when separated from its family. As a puppy grows and matures, this problem can become a major issue (such as excessive attachment, dysfunctional attachment). In fact, by regularly leaving a puppy alone during the day (for example, in a safe shelter), the likelihood of the problem occurring can be reduced. In other cases, the anxiety about being left alone stems from events such as changes in the family or the dog's daily life, or is related to the underlying state of anxiety along with other behavioral problems such as noise phobia or separation anxiety. Anxiety can lead to destructive behavior (such as heading towards an exit or the owner's possessions), vocalization of distress, soiling the house, salivation, pacing, restlessness, inability to settle down, loss of appetite, and repetitive or compulsive behavior. Such behavior appears when the dog is left alone and usually occurs within the first 15 to 30 minutes after departure. Many pets with separation anxiety disorder start showing signs when the owner is preparing to leave (such as putting on shoes, getting the keys, walking towards the door, etc.). When the owner is at home, the dog may crave constant contact or proximity to the owner. When the owner returns, the welcoming reaction is generally exaggerated and the dog is difficult to calm down.

[0022] Aggressiveness

[0023] Aggressiveness refers to threatening behaviors or harmful attacks, which can range from body postures, facial expressions, subtle changes in vocalizations to biting, including fear-related aggressiveness, possessive aggressiveness (resource guarding), play aggressiveness, redirected aggressiveness, irritable / oppositional / impulsive control aggressiveness, aggressiveness towards other dogs, territorial / protective aggressiveness, and predatory aggressiveness.

[0024] (Example)

[0025] Example 1: Preparation of PS128 Lactobacillus plantarum subsp. plantarum PS128 (hereinafter also referred to as PS128) used in this study was a strain isolated and deposited with the DSMZ accession number DSM28632. PS128 was inoculated into a medium (10% skim milk, 1% yeast powder, 0.1% Tween 80, and 2% glucose), cultured at 37 °C for 18 hours, and recovered by centrifugation. PS128 was embedded with a cryoprotectant (1% skim milk, 2% sugar, 2% oligofructose, 3% maltodextrin, and 2% glycerol), and an excipient was added, followed by lyophilization to a final concentration of 5×10 10 colony-forming units (CFU) per gram of powder.

[0026] Example 2: Treating abnormal emotions and behaviors with PS128 A total of 20 dogs were examined at a veterinary clinic for abnormal emotions and behavior. They were evaluated and scored by specialized veterinarians using the Canine Behavior Checklist (Table 1) and the Evaluation of Canine Emotional Disorders (EDED) Scale (Table 2). The checklist and EDED scale are used by veterinarians to evaluate abnormal emotions and behavior in dogs (Landsberg G., Hunthausen W., Ackerman L., 2013, Behavior Problems of the Dog and Cat. Saunders, Edinburgh 2013, Elsevier Ltd). A total score was calculated for each dog. The tested dogs were further examined by veterinarians to rule out abnormal behavior due to illness, such as abnormal thyroxine levels.

[0027] [Table 1] TIFF0007714464000002.tif254169TIFF0007714464000003.tif34169

[0028] [Table 2] TIFF0007714464000005.tif252169 TIFF0007714464000006.tif68169

[0029] Dogs were evaluated for abnormal emotions and behaviors at a veterinary clinic and then given PS128 at a dose of 0.02 g / kg body weight / day for 2 weeks. After 2 weeks of PS128 treatment, dogs were again evaluated for abnormal emotions and behaviors using the same behavioral checklist and EDED scale. The results of the behavioral checklist are summarized in Figure 1, and the results of the EDED scale are shown in Figure 2. Total scores from the evaluations before and after PS128 treatment were recorded and analyzed.

[0030] As shown in FIGS. 1 and 2, compared with before PS128 administration, the total scores of both the canine behavior checklist and the EDED scale after PS128 administration significantly decreased, indicating the effect of PS128 in preventing and treating abnormal emotions and behaviors in these companion animals.

[0031] Although some embodiments of the present disclosure have been described in detail above, those skilled in the art can make various modifications and changes to the disclosed embodiments without substantially departing from the teachings and advantages of the present disclosure. Such modifications and changes are included within the spirit and scope of the disclosure as set forth in the appended claims.

Claims

1. A pharmaceutical composition for improving a score or value for evaluating abnormal emotions or behaviors in dogs, comprising Lactobacillus plantarum subsp. plantarum PS128 deposited under DSMZ accession number DSM 28632, wherein the evaluation includes an evaluation of emotional disturbance in dogs (EDED), the EDED value of the dog decreases, pharmaceutical composition.

2. The Lactobacillus plantarum subsp. plantarum PS128 has an activity of at least 10 ７ 10. The pharmaceutical composition of claim 1, wherein the composition is orally administered to the dog in an amount of 0.1 to 1.5 CFU.

3. The pharmaceutical composition according to claim 1, wherein the Lactobacillus plantarum subsp. plantarum PS128 is orally administered to the dog at a dose of at least 0.01 g / kg body weight / day.

4. The pharmaceutical composition according to claim 1, wherein the dog is administered for at least one week.

5. The evaluation includes scoring of a dog behavior checklist, the score of the dog behavior checklist decreases, the dog behavior checklist is as shown in the following table: 【Table 1】 as shown by the pharmaceutical composition according to claim 1.

Images