Bifidobacterium longum subsp. infantis pb18 and its use for improving depression and anxiety

Abstract

The present application belongs to the technical field of microorganisms, and particularly relates to Bifidobacterium longum subsp. infantis PB18 and application thereof in improving depression and anxiety-like behavior. The taxonomic name of the Bifidobacterium longum subsp. infantis PB18 of the present application is Bifidobacterium longum subsp. infantis, and the preservation number is GDMCC No: 67093. The strain provided by the present application is safe and effective, and has an anti-depression and anti-anxiety effect. The strain PB18 provided by the present application can be used for preparing a functional probiotic product with the functions of relieving emotional stress, tension, improving depression and anxiety, autism and social phobia, insomnia and anxiety, etc.

Description

Technical Field

[0001] This invention belongs to the field of microbial technology, specifically relating to Bifidobacterium longum subsp. infantis PB18 and its application in improving stress-induced depression and anxiety-like behaviors. Background Technology

[0002] Depression can be divided into two main types: endogenous depression and exogenous / reactive depression. The main characteristic of endogenous depression is the absence of obvious external triggers, and it is mostly related to the disorder of physiological mechanisms such as abnormalities in neurotransmitters, endocrine and metabolism in the body; while stress-induced depression is triggered by a clear external event, also known as reactive depression, and is often caused by long-term negative life events, social pressure or environmental stimuli.

[0003] Chronic unpredictable mild stress (CUMS) is a classic animal model simulating stress-induced depression, characterized by its long duration and unpredictable occurrence. Individuals exposed to this type of stress over a long period gradually lose their psychological and physiological regulatory abilities, remaining in a persistent "fight or flight" state of high stress. This leads to neurotransmitter imbalances, neuroendocrine dysfunction, and immunosuppression, significantly increasing the risk of mental disorders such as depression and anxiety. The mouse model of chronic unpredictable mild stress (CUMS) is a commonly used experimental tool.

[0004] Recent studies have found that depression is not only an important type of stress-related mental disorder, but also closely related to chronic inflammation. Epidemiological data show that approximately 20%–30% of patients with depression have systemic inflammatory responses, manifested by elevated levels of C-reactive protein and pro-inflammatory cytokines in peripheral blood; individuals with chronic inflammatory diseases (such as rheumatoid arthritis, inflammatory bowel disease, and metabolic syndrome) have a 2–3 times higher risk of developing depression than the general population. Further research indicates that inflammatory responses can affect neurotransmitter metabolism and neuroplasticity through pathways such as activating the immune system and upregulating pro-inflammatory factors (such as IL-6, TNF-α, and IL-1β), thereby participating in the development of depressive-like behaviors. Clinically, some anti-inflammatory treatments (including COX-2 inhibitors and probiotic interventions) have been shown to improve mood symptoms in patients with treatment-resistant depression, suggesting that so-called "inflammatory depression" has a relatively independent pathological mechanism and potential therapeutic targets. The lipopolysaccharide (LPS)-induced mouse inflammatory depression model has become an important experimental tool for studying inflammation-related depression.

[0005] Invention CN120758413A, entitled "A strain of Bifidobacterium longum subsp. aFMT-103, its microbial preparation and its application in antidepressant treatment," discloses that: Bifidobacterium longum subsp. aFMT-103 strain was isolated from the feces of healthy adults and classified as... Bifidobacterium longum subsp.longum Using a mouse model of chronic unpredictable mild stress (CUMS), this study aimed to evaluate the effects of strain aFMT-103 on depressive-like behaviors and related biochemical indicators, verify its antidepressant efficacy, and explore whether the strain alleviates physiological damage induced by chronic stress by regulating the hypothalamic-pituitary-adrenal axis (HPA axis).

[0006] The strain used in the invention CN118256397B9, "Bifidobacterium breve, microecological preparations and their application in antidepressants," is Bifidobacterium breve. Bifidobacterium breve The sample was isolated from the breast milk of healthy adults in Zhangpu Town, Kunshan City, Jiangsu Province (accession number CGMCC No. 24982). By constructing a CUMS-induced depression mouse model, fluoxetine was selected as a positive drug control to evaluate the intervention effect of Bifidobacterium breve in the depression model mouse.

[0007] Invention CN116064326B, entitled "A strain of Bifidobacterium animalis subsp. lactis GBW8051 capable of alleviating depressive mood and its application," provides a strain of Bifidobacterium animalis subsp. lactis GBW8051 capable of alleviating depressive mood. A sample of yogurt from Qinghai was selected, and the strain was classified and named Bifidobacterium animalis subsp. lactis. Bifidobacterium animalis subsp.lactis The accession number is CCTCCNO: M 20221402. Bifidobacterium animalis subsp. lactis GBW805 can alleviate cuMS-induced anhedonia in mice.

[0008] The invention CN120437178A, entitled "An animal Bifidobacterium with the effect of improving depression and its application", states that: by establishing a mouse model of depression through injection of LPS injection solution, the forced swimming experiment shows that Bifidobacterium CP-9 has a preventive effect on depression in mice.

[0009] The invention CN120738065A, "A Compound Probiotic for Alleviating Anxiety Behavior and Its Application," discloses that Bifidobacterium animalis YRK-12 (which enhances the intestinal barrier) and Lactobacillus rhamnosus LRa-Y8 (which inhibits microglia activation and regulates neurotransmitters) form a precise complement on the "gut-brain axis." The two work synergistically to cover the entire chain of anxiety pathology.

[0010] The invention CN102946891B, "Probiotic Bifidobacterium Strains," discloses the use of a Bifidobacterium strain (accession number NCIMB 41676) in the preparation of formulations for the prevention and / or treatment of bipolar disorder, depression, mood disorders, and / or anxiety disorders.

[0011] The invention CN120718816A, entitled "A Bifidobacterium breve and its application in alleviating Alzheimer's disease," conducted nesting behavior experiments, open field experiments, and Morris water maze experiments on APP / PS1 mice (Alzheimer's disease), thereby demonstrating that intervention with Bifidobacterium breve LE4 improved the memory ability of APP / PS1 mice, alleviated changes in anxiety behavior and daily living abilities, and has the potential to be applied in products for adjunctive treatment of Alzheimer's disease. Summary of the Invention

[0012] The technical problem to be solved by the present invention is to provide a method for effectively improving depression and anxiety-like behaviors induced by chronic unpredictable stress by Bifidobacterium longum subspecies PB18.

[0013] To address the aforementioned technical problems, this invention provides a *Bifidobacterium longum* subsp. *infantii* PB18, the taxonomic name of which is... Bifidobacterium longum subsp.infantis, accession number GDMCC No: 67093.

[0014] The present invention also provides the application of strain PB18 in the preparation of drugs that improve depression and anxiety (improve depression and anxiety-like behavior) and relieve stress.

[0015] An improvement to the application of this invention: for improving stress-induced depressive and anxiety-like behaviors.

[0016] As a further improvement to the application of this invention: it can not only improve mood disorders induced by chronic unpredictable stress (CUMS), but also alleviate (significantly alleviate) anxiety-like and depression-like behaviors in a lipopolysaccharide (LPS)-induced inflammatory depression model.

[0017] The Bifidobacterium longum infant subspecies PB18 of the present invention has a wider range of applications compared to the Bifidobacteria disclosed in the background art.

[0018] The antidepressant effects of existing strains are limited to either chronic unpredictable stress (CUMS) models, LPS models, or APP / PS1 mice (Alzheimer's disease). It should be noted that, as is common knowledge in the industry, CUMS models primarily target depressive or anxiety-like behaviors induced by psychological stress, while LPS models target lipopolysaccharide (LPS)-induced inflammatory depression.

[0019] This invention has the following technical advantages: 1. This invention confirms that Bifidobacterium longum infantis subspecies PB18 can not only improve CUMS-induced mood disorders, but also significantly alleviate anxiety-like and depression-like behaviors in an LPS-induced inflammatory depression model, indicating that it has a broad-spectrum intervention effect across models and pathological mechanisms.

[0020] 2. High potential clinical translational value: Because it has shown significant improvement in both stress-induced depression and inflammatory depression, the Bifidobacterium longum infant subspecies PB18 of this invention is expected to be applied to the prevention and treatment of various types of depression and anxiety-related mood disorders, especially in patients with immune activation or intestinal inflammation, demonstrating high potential for clinical application.

[0021] The *Bifidobacterium longum* subsp. infantis PB18 of this invention further demonstrated a significant improvement in depressive-anxiety-like behaviors in an LPS-induced inflammatory depression model, indicating that the strain of this invention has stable intervention effects in both stress-induced and inflammatory depression models with different pathological mechanisms. The *Bifidobacterium longum* subsp. infantis PB18 of this invention has a wider range of applications, capable of simultaneously improving CUMS-induced and LPS-induced mood disorders, demonstrating unique technical advantages and potential clinical value. Attached Figure Description

[0022] The specific embodiments of the present invention will be further described in detail below with reference to the accompanying drawings.

[0023] Figure 1 This is a colony diagram of Bifidobacterium longum subsp. infantis PB18.

[0024] Figure 2 This is a growth curve of Bifidobacterium longum infantis subspecies PB18.

[0025] Figure 3 Flowchart for establishing and intervening in a CUMS-induced depression model: A mouse depression-like model was established using chronic unpredictable stress (CUMS). After the model was confirmed to be successful by behavioral assessment, PB18 was administered for 2 weeks, and behavioral assessment was performed again to verify the efficacy.

[0026] Figure 4 A schematic diagram of an anxiety- and depression-like behavioral experiment; Figure 4 middle: a: Open Field Test (OFT); b: Elevated Cross Maze Test (EPM); c: Forced swimming test (FST); d: Tail Suspension Test (TST).

[0027] Figure 5The effect of PB18 on improving CUMS-induced anxiety-like behavior; Figure 5 middle: a: Exploration time of mice in different groups in the central region during the open field test; PB18 intervention significantly improved the reduction in CUMS-induced central region exploration time; b: Exploration time of mice in different groups in the elevated cross maze test in the open arm; PB18 intervention significantly improved the reduction of CUMS-induced open arm exploration.

[0028] Figure 6 The effect of PB18 on improving CUMS-induced depressive-like behavior; Figure 6 middle: a: Immobility time in different groups of mice during the forced swimming test; PB18 intervention significantly reduced the increase in CUMS-induced immobility time; b: Immobility time of mice in different groups during the tail suspension test; PB18 intervention significantly reduced the CUMS-induced prolongation of immobility time.

[0029] Figure 7 The effect of PB18 on improving LPS-induced anxiety-like behavior; Figure 7 middle: a: Exploration time in the central region of mice in different groups during the open field test; PB18 intervention significantly improved the LPS-induced reduction in central region exploration time; b: Exploration time of mice in different groups in the elevated cross maze test in the open arm; PB18 intervention significantly improved the reduction of LPS-induced open arm exploration.

[0030] Figure 8 The effect of PB18 on improving LPS-induced depressive-like behavior; Figure 8 middle: a: Immobility time in different groups of mice during the forced swimming test; PB18 intervention significantly reduced the increase in LPS-induced immobility time; b: Immobility time in different groups of mice during the tail suspension test; PB18 intervention significantly reduced the LPS-induced prolongation of immobility time. Detailed Implementation

[0031] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto: In the following embodiments, unless otherwise specified, the operation methods used are conventional operation methods, the equipment used are conventional equipment, and the equipment and materials used in each embodiment are the same.

[0032] Example 1: Obtaining Bifidobacterium longum subsp. infantis PB18: Human intestinal isolates from Hangzhou were used as samples. After serial dilution with physiological saline, the isolates were spread on MRS medium and anaerobic cultured at 37°C. Single colonies were picked and expanded. After sequencing and homology comparison, Bifidobacterium longum subsp. infantis PB18 was obtained.

[0033] Morphological identification of Bifidobacterium longum subsp. infantis PB18: Gram positive, non-spore-forming, long rod-shaped, curved, forked, with smooth, convex, intact edges, creamy to white, shiny and soft in texture.

[0034] The 16S rDNA sequence identification results are shown in SEQ ID NO:1.

[0035] Subsequently, through comparison with the website of the National Center for Biotechnology Information (NCBI), it was confirmed to be the genus *Bifidobacterium longum* subsp. *infantii*, and named it *Bifidobacterium longum* subsp. *infantii*. Bifidobacterium longum PB18.

[0036] The preservation information is as follows: Bifidobacterium longum subsp.infantis PB18, Collection Name: Bifidobacterium longum subsp.infantis, deposited at: Guangdong Provincial Center for Microbial Culture Collection, deposited at: 5th Floor, Building 59, No. 100 Xianlie Middle Road, Guangzhou, deposited on: October 13, 2025, deposit number: GDMCC No: 67093.

[0037] Growth curve determination of the strain: Bifidobacterium longum subsp. infantis PB18 was inoculated into MRS liquid medium and cultured at 37°C under anaerobic conditions. The absorbance of the cultured bacteria at a wavelength of 600 nm was measured every 2 hours. The results are as follows: Figure 2 As shown in the growth curve of Bifidobacterium longum subsp. infantis PB18, it can be seen that 0h~2h is the lag phase, 2h~12h is the logarithmic growth phase, 12h~22h is the plateau phase, and decline begins after 22h.

[0038] Antibiotic susceptibility testing of strains: After activation, strain PB18 was anaerobically cultured in MRS medium until the late logarithmic growth phase. A suspension (normalized to 0.5 McFarland units) was then evenly spread onto agar plates using a glass spreader. Subsequently, standard antibiotic susceptibility testing discs containing five commonly used clinical antibiotics were placed on the plates. After anaerobic incubation at 37°C for 24–48 hours, the diameter of the inhibition zone around each antibiotic disc was precisely measured and recorded. The interpretation of the results strictly followed the relevant guidelines of the Clinical and Laboratory Standards Institute (CLSI) or the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to determine the susceptibility of the strain to each antibiotic. The experimental results are shown in Table 1.

[0039] Table 1. Antibiotic susceptibility results (inhibition zone diameter / mm)

[0040] Note: S indicates sensitive; I indicates moderately sensitive; R indicates insensitive.

[0041] Experimental results showed that *Bifidobacterium longum* subsp. infantis PB18 exhibited high sensitivity to five commonly used clinical antibiotics, providing important evidence for its combination therapy and safe clinical application. This characteristic not only ensures that the strain can be effectively controlled by conventional antibiotics during use, reducing potential application risks, but also lays the foundation for developing probiotic preparations that can be used in synergy with antibiotics, further broadening its application prospects in the comprehensive intervention of depression, anxiety, and stress-related mood disorders.

[0042] Example 2: Antibacterial test of Bifidobacterium longum subsp. infantis PB18: The inhibition zone diameter was measured using the Oxford cup agar diffusion method to assess the inhibitory effect of Bifidobacterium on indicator bacteria. Escherichia coli ATCC8739 and Staphylococcus aureus ATCC6538 were used as indicator bacteria. The antibacterial effect of the supernatant (unadjusted / pH adjusted to 7.0) filtered after 24 hours of Bifidobacterium culture was evaluated against these two pathogens. Penicillin-streptomycin was used as a positive control, and MRS medium was used as a control group. The results are shown in Table 2. Bifidobacterium metabolites showed inhibitory effects on all pathogens, and the inhibitory effect was good.

[0043] The specific preparation process of the supernatant after 24 hours of Bifidobacterium filtration is as follows: One loopful of Bifidobacterium longum subsp. infantum PB18 is inoculated into 5 ml of MRS liquid culture medium and anaerobically cultured at 37°C for 24 hours. Then, it is filtered through a 0.22 μm filter, and the filtrate is collected to obtain the supernatant after 24 hours of Bifidobacterium filtration.

[0044] Table 2. Results of antibacterial test (diameter of inhibition zone / mm)

[0045] Experimental Example 3: Determination of acid and bile salt tolerance of Bifidobacterium longum subsp. infantis PB18 I. Acid Resistance Test: A suspension of activated and expanded *Bifidobacterium longum* subsp. *infantii* PB18 was inoculated into MRS liquid medium at a concentration of 1% (v / v). After anaerobic culture at 37°C until the logarithmic growth phase, the cells were collected by centrifugation for 5 min. The cells were washed twice with phosphate-buffered saline (pH 6.8), and then resuspended in MRS liquid medium at pH 3.0 and pH 1.0. The initial viable count was corrected to approximately 10⁻⁶ cells / mL. 8 CFU / mL, anaerobic incubation at 37℃ for 0 h and 3 h. Viable bacteria in the 0 h and 3 h samples were counted using the plating method to determine the survival rate. The survival rate was calculated using the following formula: N0 represents the viable cell count (CFU / mL) of the test strain after 0 hours of anaerobic culture; N t To test the viable cell count (CFU / mL) of the strain after anaerobic culture for 3 hours;

[0046] Table 3 Results of acid tolerance of the strains

[0047] II. Determination of tolerance to bile salts (sodium taurocholate): The activated and expanded suspension of *Bifidobacterium longum* subsp. infantis PB18 was inoculated into MRS liquid medium at a concentration of 1%, and after anaerobic culture at 37°C until the logarithmic growth phase, the culture was vortexed to adjust the initial viable count to approximately 10⁻⁶. 8 CFU / mL. 10% of the sample was inoculated into MRS liquid medium containing 0.3% and 0.5% (m / v) ox bile salts, with MRS liquid medium without ox bile salts used as a control. The samples were anaerobically cultured at 37°C for 3 hours. The viable bacterial count was then determined using the spread plate method. The survival rate was calculated using the following formula: N t The number of viable bacteria of the test strain after anaerobic culture for 3 hours at the corresponding bile salt concentration; N0 is the number of viable bacteria (CFU / mL) of the test strain at a bile salt concentration of 0%;

[0048] Table 4 Results of strain tolerance to bile salts

[0049] Example 4: Preparation of Bifidobacterium longum subsp. infantis PB18 bacterial suspension: To ensure consistency in the dosage form, the preparation method for Bifidobacterium longum subsp. infantis PB18 is as follows: Bifidobacterium longum subsp. infantis PB18 was inoculated into liquid MRS medium and cultured statically in an anaerobic environment for 24 h. The bacterial cells were collected by centrifugation at 3000 rpm and 4 °C for 10 min, washed with PBS buffer (pH 7.2), resuspended in physiological saline, and diluted 5-fold. The absorbance (OD) was measured at 600 nm. 600 Approximately 1.0 μL of the suspension was used in animal experiments to treat CUMS model mice with Bifidobacterium longum subsp. infantis PB18, and the improvement in anxiety and depression-like behaviors was evaluated. 300 μL was administered to each mouse via gavage once daily for two weeks.

[0050] Example 5 (1) Preparation of WT mice Twenty-four 8-week-old wild-type C57BL / 6J mice were purchased from Hangzhou Medical College and housed in an SPF barrier system. After one week of acclimatization, they were randomly divided into two groups: a normal control group (n=8, not subjected to stress) and a chronic unpredictable stress (CUMS) group (n=16, modeled).

[0051] (2) Establishing the CUMS model and behavioral assessment Following the CUMS paradigm, mice were exposed to the following stimuli in a randomized, non-repeated manner over 4 weeks: 1) 24-hour fasting and water deprivation; 2) 6-hour restraint stress; 3) 24-hour odor stimulation; 4) 24-hour wet mat; 5) tail clamping for 60 seconds; 6) swimming in 4°C cold water for 5 minutes; 7) cage tilting at 45° for 6 hours; 8) 24-hour matless exposure; 9) horizontal shaking for 10 minutes; 10) stroboscopic flashing for 12 hours; 11) circadian rhythm reversal for 24 hours; and 12) white noise for 12 hours. Behavioral assessments were conducted after 4 weeks of model establishment to determine the success of the model. Figure 3 ).

[0052] The behavioral assessment was conducted with reference to the published "What's Wrong With My Mouse: Behavioral Phenotyping of Transgenic and Knockout Mice".

[0053] Anxiety-like behaviors were assessed using the open field test (OFT) and the elevated cross maze test (EPM), with the exploration time in the central area of ​​the open field and the dwell time (within 5 min) in the open arm recorded. Depression-like behaviors were assessed by recording the immobility time in the last 4 minutes of the forced swimming test (FST) and the tail suspension test (TST). Figure 4 ).

[0054] Successful model establishment was verified: Compared with the normal control group, the immobility time of FST and TST in the CUMS group was significantly prolonged.p <0.05, the dwell time in the OFT central area and the dwell time in the EPM open arm were significantly reduced ( p <0.05 indicates that depressive-anxiety-like behavior was successfully induced.

[0055] (3) Grouping and intervention with Bifidobacterium longum infant subspecies PB18 After successful behavioral modeling verification, CUMS mice were randomly divided into two groups: the CUMS-Vehicle group (administered with an equal volume of physiological saline by gavage) and the CUMS-PB18 group (administered with a suspension of Bifidobacterium longum subsp. infantis PB18 prepared in Example 4 by gavage, once daily, with each mouse receiving 300 μL per administration for 2 consecutive weeks). During the intervention period, the normal control group maintained routine feeding and was not subjected to stress, but was only administered an equal volume of physiological saline by gavage.

[0056] After two weeks of intervention, all mice underwent behavioral assessments again, namely, anxiety-like behavior was assessed by open field and elevated cross maze tests, and depression-like behavior was assessed by forced swimming and tail suspension tests.

[0057] Intervention effect: Compared with the CUMS-Vehicle group, the CUMS-PB18 group showed significantly longer OFT central area dwell time and EPM open arm dwell time, indicating a significant improvement in anxiety-like behavior. p <0.05)( Figure 5 ), while the immobility time of FST and TST was significantly reduced ( p <0.05, indicating that depressive-like behavior was also alleviated ( Figure 6 ).

[0058] (4) Conclusion The above results indicate that oral administration of Bifidobacterium longum infant subspecies PB18 significantly alleviated depressive-like and anxiety-like behavioral phenotypes in the CUMS model, suggesting that Bifidobacterium longum infant subspecies PB18 has potential value in alleviating stress-induced depressive-anxiety-like behaviors.

[0059] It should be noted that: Bifidobacterium CP-9, Bifidobacterium animalis YRK-12, Bifidobacterium strain (accession number NCIMB 41676), and Bifidobacterium breve LE4 were all prepared into corresponding bacterial suspensions (OD). 600 Approximately 1.0), and then tested according to the method described in Example 5 above. The residence time in the central region of the OFT and the residence time in the open arm of the EPM were not significantly different from those in the CUMS-Vehicle group; furthermore, the immobility times of the FST and TST were also not significantly different from those in the CUMS-Vehicle group. Note: The above strains did not improve anxiety-like and depression-like behaviors induced by the CUMS model.

[0060] Example 6 (1) Preparation of WT mice Twenty-four 8-week-old wild-type C57BL / 6J mice were purchased from Hangzhou Medical College and housed in an SPF barrier system for one week of acclimatization.

[0061] (2) LPS intraperitoneal injection and intervention with Bifidobacterium longum infant subspecies PB18 After the adaptation period, the mice were randomly divided into three groups (n=8 per group): Normal control group: No stress or drug intervention; that is, 300 μL of normal saline was administered by gavage for 5 consecutive days; from day 6 onwards, the same volume of normal saline was injected intraperitoneally and 300 μL of normal saline was administered by gavage daily for 5 consecutive days.

[0062] LPS-Vehicle group: 300 μL of normal saline was administered by gavage for 5 consecutive days; from day 6 onwards, LPS (0.5 mg / kg) was injected intraperitoneally daily and 300 μL of normal saline was continued by gavage for 5 consecutive days.

[0063] LPS-PB18 group: 300 μL of Bifidobacterium longum subsp. infantis PB18 suspension was administered by gavage for 5 consecutive days; from day 6 onwards, LPS (0.5 mg / kg) was injected intraperitoneally daily and 300 μL of PB18 suspension was administered by gavage for 5 consecutive days.

[0064] Thus, an LPS-induced inflammatory depression model was established.

[0065] (3) Behavioral assessment After the intervention, all mice underwent behavioral tests. Anxiety-like behaviors were assessed using the Open Field Test (OFT) and the Elevated Cross Maze Test (EPM); depression-like behaviors were assessed using the Forced Swimming Test (FST) and the Suspended Tail Test (TST).

[0066] Compared with the LPS-Vehicle group, the LPS-PB18 group mice had significantly longer dwell times in the OFT central area and EPM open arm. p < 0.05 indicates a significant improvement in anxiety-like behavior ( Figure 7 Meanwhile, the immobility time in FST and TST was significantly reduced ( p < 0.05) indicates that depressive-like behavior has been alleviated ( Figure 8 ).

[0067] (4) Conclusion The above results indicate that oral administration of Bifidobacterium longum infantis subsp. PB18 can significantly improve the anxiety-like and depression-like behavioral phenotypes in LPS-induced mice, suggesting its potential intervention value in alleviating inflammatory depression-related mood disorders.

[0068] It should be noted that: *Bifidobacterium longum* subsp. *aFMT-103*, *Bifidobacterium breve* (CGMCC No. 24982), and *Bifidobacterium animalis* subsp. *lactobacter* GBW8051 were all prepared into corresponding bacterial suspensions (OD). 600 Approximately 1.0), and then tested according to the method described in Example 6 above. The residence time in the OFT central region and the residence time in the EPM open arm were not significantly different compared to the LPS-Vehicle group; furthermore, the immobility time in FST and TST was also not significantly different compared to the LPS-Vehicle group. Note: The above strains did not improve anxiety-like and depression-like behaviors induced by the LPS model.

[0069] Finally, it should be noted that the above examples are merely some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments and many variations are possible. All variations that can be directly derived or conceived by those skilled in the art from the disclosure of the present invention should be considered within the scope of protection of the present invention.

Claims

1. Bifidobacterium longum subsp. infantis, used to improve depression and anxiety and relieve stress ( Bifidobacterium longum subsp.infantis)PB18, characterized by: The taxonomic name of strain PB18 Bifidobacterium longum subsp.infantis, accession number GDMCC No: 67093.

2. The application of *Bifidobacterium longum* subsp. infantis PB18 as described in claim 1 in the preparation of a drug for improving depression and anxiety and relieving stress, characterized in that: It can not only improve mood disorders induced by chronic unpredictable stress, but also alleviate anxiety-like and depression-like behaviors in a lipopolysaccharide-induced inflammatory depression model.

3. The application according to claim 2, characterized in that: It is used to improve stress-induced depression and anxiety-like behaviors.

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