WO2020037531A1 - Procédé de criblage au niveau cellulaire de probiotiques qui réalisent une fonction antidépressive au moyen de la voie associée au 5-hydroxytryptophane - Google Patents

Procédé de criblage au niveau cellulaire de probiotiques qui réalisent une fonction antidépressive au moyen de la voie associée au 5-hydroxytryptophane Download PDF

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WO2020037531A1
WO2020037531A1 PCT/CN2018/101684 CN2018101684W WO2020037531A1 WO 2020037531 A1 WO2020037531 A1 WO 2020037531A1 CN 2018101684 W CN2018101684 W CN 2018101684W WO 2020037531 A1 WO2020037531 A1 WO 2020037531A1
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probiotics
hydroxytryptophan
screening
cells
related pathway
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王刚
陈卫
田培郡
赵建新
张灏
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Jiangnan University
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales

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  • the invention relates to the technical field of probiotic screening, and in particular to a method for screening a probiotic that achieves an antidepressant function through a 5-hydroxytryptophan-related pathway based on a cell level.
  • Depression also known as depressive disorder, is characterized by significant and persistent depression. Currently, more than 350 million people worldwide suffer from depression. It is estimated that by 2030, depression will rank first in the global burden of disease. A large number of studies have shown that the occurrence of depression is related to the disorder of monoamine neurotransmitters in the brain, which is mainly manifested by the reduction of serotonin (5-HT) concentration in the cerebral synaptic cleft.
  • the current treatments for depression are mainly focused on increasing 5-HT levels in the brain, such as selective first-line antidepressants-selective serotonin reuptake inhibitors (SSRI).
  • 5-HT Tryptophan the precursor of 5-HT, also has certain antidepressant effects, but because of its short half-life in the human body, it cannot be used as a clinical drug.
  • the current treatments for depression are focused on increasing 5-HT levels in the brain.
  • Brain-gut axis is a new concept proposed in recent years. As a two-way communication system between intestinal bacteria and the brain, it mainly regulates brain functions and behaviors through neural, endocrine and immune pathways. Studies have shown that the intestinal flora of depressed patients will change, and animal experiments have found that the depressive symptoms of sterile mice can be reduced, which proves that the intestinal flora is related to the occurrence and development of depression. Regulation of intestinal flora through probiotics can be a new way to alleviate depression.
  • the present invention provides the following technical solution: a method for screening probiotics that achieve antidepressant function through a 5-hydroxytryptophan-related pathway based on a cell level, including:
  • Cell culture the cells are capable of expressing tryptophan hydroxylase 1 and secreting 5-hydroxytryptophan;
  • the cells are treated with bovine serum albumin and fluoxetine, they are incubated with probiotics to screen probiotics with antidepressant function.
  • the cells include rat islet tumor cells RIN14B.
  • the cell culture As a preferred scheme of the method for screening probiotics that achieve antidepressant function through a 5-hydroxytryptophan-related pathway according to the present invention: the cell culture, wherein the cell culture medium includes RPMI1640 medium.
  • the probiotics include Bifidobacterium, Lactobacillus, Streptomyces Coccus, Lactococcus, Leuconostoc, Propionibacterium, Pediococcus, Bacillus.
  • the screen has antidepressant effects through a 5-hydroxytryptophan-related pathway probiotic function, including, cells were passaged 10 5 ⁇ 10 6 / mL were seeded in 24-well plates, the cells were washed with Hank's balanced salt solution containing 0.1% bovine serum albumin and 1-4 ⁇ mol / L fluoxetine, after Add HBSS suspension containing different probiotics, adjust the concentration of probiotics to 10 7 -10 9 cfu / mL, and incubate at 37 ° C for 20min, collect the suspension, centrifuge at 5000 ⁇ 6000g for 5 ⁇ 10min to remove the precipitate, and take the supernatant to wait Measurement.
  • the screen has antidepressant effects through a 5-hydroxytryptophan-related pathway
  • Functional probiotics include the detection of 5-hydroxytryptophan secreted by the cells and the mRNA level of tryptophan hydroxylase 1 in the cells after incubation with the probiotics.
  • the secreted amount of 5-hydroxytryptophan in the cell is increased by 10 times.
  • the above probiotic strains were used as effective strains for screening.
  • the secreted amount of 5-hydroxytryptophan is a fluorescent high-performance liquid Chromatographic analysis.
  • the tryptophan hydroxylase 1 mRNA is increased by more than 50% in probiotics.
  • Bacterial strains as effective strains.
  • the mRNA level of the tryptophan hydroxylase 1 is detected by qPCR .
  • the present invention uses RIN14B cells as a screening model. After treatment with fluoxetine, adding probiotics for incubation, taking the cell supernatant to detect the content of 5-HTP, and lysing the cells to detect its tryptophan hydroxylation Tryptophan hydroxylase1 (TPH1) mRNA expression to determine whether probiotics can promote intestinal cells to produce 5-hydroxytryptophan (5-HTP), a neurotransmitter precursor, and thus exert antidepressant effects efficacy.
  • TPH1 tryptophan hydroxylation Tryptophan hydroxylase1
  • the experiment proves that the probiotics can stimulate the intestinal chromaffin cells to secrete 5-HTP continuously and slowly through colonization of the intestine, thereby providing precursor substances for the synthesis of 5-HT in the brain and achieving antidepressant effects.
  • the present invention uses "simulated intestinal chromaffin cells" (that is, RIN14B cells) to detect 5-HTP secretion and TPH1 mRNA expression through probiotic stimulation to screen probiotics with antidepressant functions. The validity of the screening model was verified in animal experiments.
  • the invention provides a method for quickly and efficiently screening anti-depressant probiotic strains based on the 5-HTP pathway.
  • Figure 1 shows the chromatographic retention time and standard curve of 5-HTP.
  • A Chromatographic retention times of 5-HTP and 5-HT;
  • B 5-HTP standard curve.
  • Figure 2 is a schematic diagram of the content of 5-HTP secreted by RIN14B cells stimulated by probiotics; among them, * P ⁇ 0.05, ** P ⁇ 0.01, **** P ⁇ 0.0001 (vs. control group).
  • Figure 3 is a schematic diagram of TPH1 mRNA levels in RIN14B cells after probiotic stimulation; where * P ⁇ 0.05, **** P ⁇ 0.0001 (vs. control group).
  • Figure 4 is a schematic diagram of the behavioral changes of mice in each group after probiotics interfered with depression mice for six weeks.
  • A forced swimming experiment
  • B sugar water preference experiment
  • C platform jumping experiment
  • Figure 5 is a schematic diagram of the changes in 5-HT (A) and 5-HTP (B) levels in the hippocampus of mice in each group after probiotics interfered with depression for six weeks; * P ⁇ 0.05, ** P ⁇ 0.01 (vs model group).
  • Figure 6 is a schematic diagram of the changes of BDNF levels in the prefrontal cortex of mice in each group after probiotics interfered with depression for six weeks; * P ⁇ 0.05, ** P ⁇ 0.01, *** P ⁇ 0.001 (vs model group) .
  • FIG. 7 is a schematic diagram showing changes in ACTH and corticosterone levels in serum of mice after six weeks of intervention in depressed mice; * P ⁇ 0.05 (vs model group)
  • Figure 8 is a schematic diagram of the correlation between the 5-HTP and TPH1 mRNA detection results of cells and animal experimental indicators; blue represents negative correlation and red represents positive correlation.
  • Figure 9 is a schematic diagram of indicators with significant correlation between cell models and animal experiments.
  • an embodiment or “an embodiment” referred to herein refers to a particular feature, structure, or characteristic that can be included in at least one implementation of the present invention.
  • the appearances of "in one embodiment” in various places in this specification do not all refer to the same embodiment, nor are they separate or selectively mutually exclusive embodiments.
  • Example 1 Using RIN14B cells to screen probiotics with the potential to achieve antidepressant through 5-hydroxytryptophan related pathways
  • RIN14B (ATCC CRL-2059) cells belong to a rat islet tumor cell line.
  • the medium is RPMI-1640 supplemented with 1% double antibody (100U / mL penicillin and 100 ⁇ g / mL streptomycin) and 10% fetal bovine serum (FBS). Complete medium (or DMEM medium).
  • the cells were cultured in a closed incubator at 37 ° C and 5% CO 2 , and the culture medium was changed every 2-3 days according to the cell growth status.
  • Cells were digested with 0.25% trypsin for passage and cryopreservation. The digestion time is 1-2min.
  • the number of generations of cells used in this example is 10-20 generations.
  • the strains used are shown in Table 1. After the strains were activated, they were inoculated in MRS liquid medium at 1% inoculation amount, cultured at 37 ° C for 20 hours, and centrifuged at 3000 rpm for 10 minutes to collect the bacterial cells. The collected bacterial cells were washed 3 times with Hank's balanced salt solution (HBSS) and resuspended in HBSS. In order to adjust the concentration of live bacteria to 2 ⁇ 10 8 CFU / mL.
  • HBSS Hank's balanced salt solution
  • RIN14B cells were seeded at a density of 4 ⁇ 10 5 / mL in a 24-well plate and incubated for 72 h. The medium was discarded, cells were washed with HBSS (1 mL) containing 0.1% bovine serum albumin (BSA) and 2 ⁇ M fluoxetine, and 1 mL of HBSS suspension containing different probiotics was added (the control group was HBSS without bacteria) Incubate at 37 ° C for 20min, collect the supernatant, centrifuge at 6000g for 5min to remove the precipitate, and freeze the supernatant at -80 ° C for measurement. HPLC-FLD detection of 5-HTP in cell supernatants:
  • 5-HTP and 5-HT mixed standard solutions Take 5-HTP and 5-HT standards (Sigma-Aldrich, Chemicals, USA) and dissolve them in 2.5% perchloric acid solution to prepare 1-g / L 5-HTP Standard stock solution. Gradient dilution methods were used to prepare 200 ⁇ g / L, 100 ⁇ g / L, 50 ⁇ g / L, 25 ⁇ g / L, 12.5 ⁇ g / L, and 6.25 ⁇ g / L standard solutions, which were filtered through 0.22 ⁇ m filters and transferred to liquid phase vials. Machine determination.
  • the retention time of the peak is used for qualitative analysis, and the peak area of the external standard method is used for quantification.
  • the 5-HTP retention time is about 4.0min
  • the 5-HT retention time is about 5.8min.
  • the peak shape of the chromatogram is stable, the baseline is stable, and no other impurities interfere with the peak. The two have a good separation effect, can accurately characterize 5-HTP, and the detection time is short. The measurement can be completed in 8 minutes.
  • a standard curve was plotted against the concentration using the peak area values detected by a series of standard solutions of 200 ⁇ g / L, 100 ⁇ g / L, 50 ⁇ g / L, 25 ⁇ g / L, 12.5 ⁇ g / L, and 6.25 ⁇ g / L (Figure 1B).
  • the peak area of the sample to be measured is brought into the formula and then multiplied by the dilution factor to obtain the 5-HTP content in the sample.
  • TPH1 tryptophan hydroxylase 1
  • Extraction of cellular RNA Take the cells in step 3, after probiotic stimulation, wash the adherent cells in the wells three times with HBSS, add 1 mL of Trizol, and incubate on ice for 5-10 min. The lysate was transferred to an enzyme-free EP tube. After adding 200 ⁇ L of chloroform and shaking to make it fully emulsified, it was left at room temperature for 15 minutes, and then centrifuged at 4 ° C and 12000 g for 15 minutes. Pipette 300-400 ⁇ L of the supernatant and transfer it to a new enzyme-free EP tube. Add an equal volume of isopropanol, gently invert and mix.
  • cDNA synthesis was performed according to the instructions of the reverse transcription kit (Prime Script RT reagent Kit gDNAEraser, Takara). The synthesized cDNA samples were tested for concentration and purity (A 260 / A 280 ) by ultra-micro spectrophotometer (NanoDrop 2000C), and stored at -80 ° C until use.
  • TPH1 mRNA measurement The samples were mixed with the fluorescent dye SYBR Green super mix (Qiagen, Germany). The PCR system was 5 ⁇ L mix, 1 ⁇ L cDNA, 1 ⁇ L forward and reverse primers, and the total volume was made up to 10 ⁇ L with dd water. Detection was performed on a real-time fluorescence quantitative gene amplification instrument CFX96 TM Real-Time System (Bio-Rad, USA). Three parallel wells were set up for each sample, and the housekeeping gene ⁇ -Actin was used as an internal reference. The results were obtained using 2 - ⁇ Cq For analysis; the primer sequences used are shown in Table 2.
  • FIG. 3 shows the TPH1 mRNA expression of RIN14B cells stimulated by different probiotics.
  • the results showed that the probiotics Bi1 and BB4 can not only increase the secretion of 5-HTP, but also increase the mRNA level of TPH1 in RIN14B cells.
  • the experimental results of TPH1 further narrowed the scope of effective bacteria.
  • probiotics capable of significantly increasing both TPH1 mRNA expression and 5-HTP secretion of RIN14B cells were identified as strains with potential antidepressant functions, namely Bi1 and BB4. Next, animal experiments were performed for verification.
  • Example 2 Animal experiment verification of effective strains for cell screening
  • mice 78 6-week-old male C57BL / 6J mice were randomly divided into four groups based on body weight after one week of adaptation: control group, model group, fluoxetine intervention group, and probiotic intervention group (intragastrically as shown in Table 1) 10 strains of probiotics), each group contains 6 mice. Animal grouping and processing methods are shown in Table 2.
  • Chronic unpredictable stress depression mouse model 1-2 stimuli are randomly used daily, and the timing of each stimulus is randomly determined to avoid circadian rhythm. Each method does not exceed three for five weeks. Stimulating factors include: (1) fasting for 24h; (2) water-free + empty bottle stimulation for 24h; (3) tail clamping for 3min; (4) wet litter for 24h; (5) braking for 1 to 2h; (6) 45 Tilt the cage for 24h at °C; (7) continuous light for 24h; (8) no litter for 24h; (9) forced swimming for 15 minutes; (10) orphanage for 24h.
  • Probiotics gavage take activated second-generation probiotics and incubate at 37 ° C for 24h, centrifuge at 3 ° C, 8000r / min for 3min to collect the bacteria, discard the supernatant and resuspend the bacteria with 5% sterilized skim emulsion , So that the probiotic concentration reaches 5 ⁇ 10 9 CFU / mL.
  • the gavage volume was 0.2 mL / piece / day.
  • the forced swimming test is a behavioral despair experiment, and it is a classic experimental model for evaluating the antidepressant effect of drugs.
  • the experimental bucket was filled with about 20 cm of clear water, and the water temperature was about 24 ⁇ 1 °.
  • Each mouse was subjected to a 15-minute swimming training test 24 hours before the official experiment. For formal experiments, each mouse was tested for 6 minutes. Use the camera to record the entire experiment. Record the immobility (floating) time, that is, the limbs are not moving or only the hind limbs are slightly moving.
  • the experimental results are shown in Figure 4A.
  • the mice in the depression group significantly reduced their swimming time in the water, showing behavioral despair. And taking Bi1 and BB4 can significantly improve this phenomenon, demonstrating the antidepressant effect of Bi1 and BB4. It has been demonstrated in Example 1 that Bi1 and BB4 can increase the expression of TPH1 mRNA and 5-HTP secretion in RIN14B cells. The results of this animal experiment are consistent with the screening results of cell models.
  • the sugar water preference test is a model for detecting a lack of pleasure in depression. Before starting the test, two identical drinking bottles were placed in the cage to allow the mice to adaptively drink water for at least 3 days. After acclimation, one of the bottles was replaced with an aqueous solution containing 1% sucrose. The water and sucrose solution intake was measured by weighing the bottle. Change the position of two bottles daily to reduce drinking preferences due to different amounts of water.
  • the platform jump test can reflect the degree of memory of passive injury and the degree of anxiety of memory recurrence in mice.
  • the first phase is the electric shock training phase. The mice were placed on the platform of the jumping platform reaction box, and the electric grid at the bottom of the reaction box was energized (38V). When the mice jumped off the platform, they received an electric shock. The training time is 3 minutes. If individual mice do not jump off the platform within 3 minutes, they will be artificially kicked off to ensure that all animals have been injured by electric shock, causing nociceptive memory. After training, return to the original cage.
  • the second phase (24h after electric shock training) is the memory reproduction test phase. Put the mouse on the platform of the reaction box.
  • the test time is 3 minutes. This test is not powered. Record the time from when the mouse jumps from the platform to the first jump (time spent on the platform), that is, the platform incubation period. The mouse has not jumped off the platform at 180s. Try to avoid human interference with animal behavior throughout the experiment.
  • the experimental results show (Figure 4C) that the depression latency of depressed mice is significantly increased, representing an increase in depression and anxiety, while taking Bi1, Bi3, BB2, BB4 and BB5 can significantly reduce the latency of depression of depressed mice, indicating that these strains Can alleviate the symptoms of depression, and can improve the anxiety symptoms associated with depression.
  • Bi1 and BB4 meet the results of cell model screening.
  • mice in Example 2 were euthanized at the sixth weekend, the brain tissues of the mice were taken, and the hippocampus and prefrontal cortex were separated on ice. Take fresh seahorse and prefrontal cortex tissues of a certain quality (weight not less than 50mg), add 9 times the volume of sterile PBS buffer (equivalent to 1g tissue plus 9ml homogenate), and homogenize with a tissue homogenizer. After the tissue fluid was centrifuged at 3000g and 20min, the supernatant was collected, and the 5-HT and BDNF contents were detected by an ELISA kit.
  • sterile PBS buffer equivalent to 1g tissue plus 9ml homogenate
  • Example 2 The mice in Example 2 were sacrificed euthanized on the sixth weekend, and the blood of the mice was collected and centrifuged at 1000 g for 15 min to obtain serum.
  • ELISA kit was used to detect the content of adreno-cortico-tropic-hormone (ACTH) and corticosterone in serum.
  • the experimental results showed that (Figure 7), due to the persistent chronic stress, the hypothalamus-pituitary-adrenal axis (HPA) hyperfunction occurred, and serum ACTH and corticosterone levels (P ⁇ 0.05) increased.
  • BB2 can significantly reduce the concentration of ACTH in serum, and taking Bi3, BB4 and LF2 can significantly reduce the level of corticosterone in serum. Among them, BB4 meets the expected results of cell experiments.
  • the 5-HTP secretion of RIN14B cells was significantly positively correlated with the sugar and water preference of mice, the shortening of the platform incubation latency, and the level of BDNF in the brain.
  • the expression of TPH1 mRNA in RIN14B cells was significantly positively correlated with the swimming time of mice and the level of BDNF in the brain (Figure 9).
  • the above results show that the probiotics screened by the RIN14B cell model with the potential to achieve antidepressant through 5-hydroxytryptophan-related pathways can be validated in animal experiments, and the results of animal experiments and cell model screening The results are significantly correlated. Therefore, using RIN14B cells as a model and assays based on 5-HTP-related pathways (TPH1 and 5-HTP) can become a fast and effective screening method for antidepressant probiotics through 5-hydroxytryptophan-related pathways.

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Abstract

L'invention concerne un procédé au niveau cellulaire pour cribler des probiotiques qui réalisent une fonction antidépressive au moyen d'une voie associée au 5-hydroxytryptophane. Les cellules RIN14B sont utilisées comme modèle de criblage, et au moyen de la co-incubation de probiotiques et de cellules, la quantité de 5-hydroxytryptophane sécrétée dans un surnageant cellulaire et le taux d'ARNm de tryptophane hydroxylase 1 dans les cellules sont mesurés de manière à déterminer des probiotiques qui peuvent exercer un effet antidépresseur au moyen du 5-hydroxytryptophane.
PCT/CN2018/101684 2018-08-22 2018-08-22 Procédé de criblage au niveau cellulaire de probiotiques qui réalisent une fonction antidépressive au moyen de la voie associée au 5-hydroxytryptophane Ceased WO2020037531A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102181449A (zh) * 2011-03-06 2011-09-14 浙江大学 表达人有机阳离子转运体1的细胞模型构建及应用
CN103087963A (zh) * 2013-01-31 2013-05-08 武汉工业学院 一种筛选益生菌的方法
CN106520603A (zh) * 2016-10-27 2017-03-22 江南大学 一种在细胞水平筛选具有增强肠道细胞紧密连接功能益生菌的方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102181449A (zh) * 2011-03-06 2011-09-14 浙江大学 表达人有机阳离子转运体1的细胞模型构建及应用
CN103087963A (zh) * 2013-01-31 2013-05-08 武汉工业学院 一种筛选益生菌的方法
CN106520603A (zh) * 2016-10-27 2017-03-22 江南大学 一种在细胞水平筛选具有增强肠道细胞紧密连接功能益生菌的方法

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHEN YI ET AL: "Changes of 5-hydroxytryptamine and Tryptophan Hydroxylase Expressions in Tissues of Depression Model Rats Induced by Chronic Low-intensity Stress", CHINA PHARMACY, vol. 28, no. 22, 10 August 2017 (2017-08-10), pages 3061 - 3064, XP055688636, ISSN: 1001-0408, DOI: 10.6039/j.issn.1001-0408.2017.22.10 *
WACLAWIKOVA: "Role of Microbiota and Tryptophan Metabolites in the Re- mote Effect of", PHARMACEUTICALS (BASEL, 25 June 2018 (2018-06-25) *
YANO: "Indigenous Bacteria from the Gut Microbiota Regulate Host Se- rotonin Biosynthesis", CELL, vol. 161, no. 2, 9 April 2015 (2015-04-09) *

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