CN113512514B - 一株具有改善抑郁功效的乳酸乳球菌及其应用 - Google Patents
一株具有改善抑郁功效的乳酸乳球菌及其应用 Download PDFInfo
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- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
本发明涉及微生物技术领域，尤其涉及一株具有改善抑郁功效的乳酸乳球菌及其应用，所述乳酸乳球菌命名为乳酸乳球菌Lactococcus lactis WHH2078，该菌株已于2021年2月25日保藏于中国微生物菌种保藏管理委员会普通微生物中心，其保藏编号为CGMCC NO.21831。本发明的乳酸乳球菌Lactococcus lactis WHH2078具备良好的黏附特性、耐酸耐胆盐特性和肠道屏障保护功能，能够显著下调血清皮质酮水平，通过回调体内抑郁相关神经因子缓解抑郁/焦虑样行为，具有显著的改善抑郁功效；发酵特性优良，可应用于发酵乳中，也可用于预防和/或治疗抑郁的药品、保健品或食品中。
Description
技术领域
本发明涉及微生物技术领域，尤其涉及一株具有改善抑郁功效的乳酸乳球菌及其应用。
背景技术
抑郁症是一种常见精神障碍疾病，患者心情郁闷，丧失兴趣或享受感，产生负罪感，或自尊心不足，睡眠和食欲紊乱，身体疲倦，注意力不易集中。抑郁症可能长期存在，或经常复发，从而严重影响个人的工作或学习能力或日常生活能力。最严重时，抑郁症可引致自杀。2020年，抑郁症已成为仅次于癌症的造成人类死亡和残疾的第二大疾病。根据世界卫生组织报道，全球约有3.5亿名抑郁症患者，我国抑郁症患者逾9500万，并呈逐年上升态势。同时，抑郁症的发病(和自杀事件)已开始出现低龄化(大学，乃至中小学生群体)趋势。抑郁症防治已被列入全国精神卫生工作重点。
目前抑郁症的病因并不明确，其发病过程可能与遗传、神经生化、环境压力等因素密切相关。预防和治疗抑郁的手段主要包括有效的心理疏导和药物治疗方法。抗抑郁药物作用原理主要是阻断脑内神经递质受体来调整脑内神经化学物质的平衡。截至2020年，全球至少有68个抗抑郁症药物上市，其中最畅销的8个为：氟西汀、帕罗西汀、舍曲林、氟伏沙明、文拉法辛、米氮平、度洛西汀和阿米替林，总销售额超过全球抗抑郁药市场的80％。然而，长期服用抗抑郁药物存在一定的副作用，例如出汗、胃肠道不适、体重上升、失眠、疲倦、神经紧张、肌肉震颤和躁郁等。
鉴于药物治疗存在的缺陷，针对抑郁、焦虑情绪寻找一种健康有效的干预或治疗途径显得意义重大。乳酸菌通常是指一类能发酵碳水化合物，且代谢产物主要为乳酸的细菌，主要包括乳酸杆菌、乳酸球菌和双歧杆菌等属内细菌。人类将乳酸菌应用于食品、饲料的发酵与保藏已有上千年之久。经科学研究证明，一些乳酸菌种属可对宿主产生益生作用，这一类乳酸菌被称为益生菌。世界卫生组织将“益生菌”定义为：当宿主摄入足够量的该类存活状态的微生物，可以促进宿主健康。近年来，国内外有大量文献报道，一些益生菌菌株针对抑郁、焦虑等具有良好的干预或治疗效果。在抑郁动物模型上的研究表明，植物乳杆菌株(Lactobacillus plantarum PS128)可有效缓解抑郁小鼠的抑郁和焦虑样行为。RamalhoB等(2019)研究发现，饲喂乳酸乳球菌株(Lactococcus lactis subsp.cremoris LL95，1×109CFU/天)4周可显著改善抑郁小鼠的抑郁样行为，具体表现为不动时间减少和自主探索时间增加。Xie等(2020)研究显示，罗伊氏乳杆菌株(Lactobacillus reuteri 3，1×109CFU/天)同样具有缓解抑郁小鼠抑郁样行为的作用，并发现该菌株通过影响小鼠色氨酸代谢以起到调节作用。Tian等(2020)研究发现，短双歧杆菌株(Bifidobacterium breveCCFM1025，1×109CFU/天)主要通过调控抑郁小鼠肠道微生物组成，影响小鼠大脑5-羟色胺能系统功能，从而缓解抑郁小鼠的抑郁样行为。此外，人群试验研究结果同样证实了一些益生菌株的改善抑郁功效。Wallace CJ等(2020)研究发现，口服乳酸乳球菌(Lactobacillushelveticus，6×109CFU/天)和长双歧杆菌(Bifidobacterium longum，6×109CFU/天)8周可显著减少重度抑郁患者的抑郁和焦虑症状。另有研究发现，口服鼠李糖乳杆菌株(Lactobacillus rhamnosus HN001，6×109CFU/天)对于产后抑郁症状具有缓解作用。根据文献调研结果发现，乳酸菌在改善抑郁方面具有一定的潜力。中国地大物博，乳酸菌资源丰富，因此，大力挖掘我国特有的具有改善抑郁功效的乳酸菌显得意义重大。
筛选得到一株能够有效干预或缓解抑郁、焦虑等症状的益生菌株，并证明该菌株在动物模型中具有良好的改善抑郁的功效，同时将这株菌应用于功能性食品产品中显得十分重要。本发明试图进一步挖掘益生菌的功能，为通过膳食方式预防或改善抑郁开辟新的有效解决途径。
发明内容
本发明为了克服上述现有技术中存在的问题，提供了一种具有改善抑郁功效的乳酸乳球菌。
本发明还提供了一种具有改善抑郁功效的乳酸乳球菌在制备预防和/或治疗抑郁的药品、保健品或食品中的应用。
为了实现上述目的，本发明采用以下技术方案：
一株具有改善抑郁功效的乳酸乳球菌，命名为乳酸乳球菌Lactococcus lactisWHH2078，该菌株已于2021年2月25日保藏于中国微生物菌种保藏管理委员会普通微生物中心，其保藏编号为CGMCC NO.21831。
上述新菌株是从我国西藏自治区日喀则市乡村采集的酸奶酥油中分离得到。
作为优选，所述乳酸乳球菌Lactococcus lactis WHH2078在HT-29细胞模型试验中单细胞黏附菌数为10.33±1.1，是对照商业菌株LGG的2.72倍。
作为优选，所述乳酸乳球菌Lactococcus lactis WHH2078在pH 3.5环境下孵育3h存活率为66.67％，在pH 3.0环境下孵育3h存活率为54.07％，在pH 2.5环境下孵育3h存活率为42.67％。
作为优选，所述乳酸乳球菌Lactococcus lactis WHH2078在0.1％胆盐浓度下孵育8h存活率为64.33％，在0.2％胆盐浓度下孵育8h存活率为51.91％，在0.3％胆盐浓度下孵育8h存活率为38.11％。
本发明的新菌株乳酸乳球菌Lactococcus lactis WHH2078具有良好的黏附性和耐酸耐胆盐能力，可以顺利通过胃肠道，并定植于肠道中，发挥益生功能。
作为优选，所述乳酸乳球菌Lactococcus lactis WHH2078在IPEC-J2细胞模型试验中，1×108CFU/mL菌株孵育细胞12h后细胞电阻值可上升89.76％，显著优于对照商业菌株LGG(70.12％)。乳酸乳球菌Lactococcus lactis WHH2078具有良好的肠道屏障保护功能。
作为优选，所述乳酸乳球菌Lactococcus lactis WHH2078的服用剂量在1×109CFU/d时，悬尾试验抑郁样行为减少18.78％，强迫游泳试验抑郁样行为减少18.66％，旷场试验焦虑样行为减少13.58％，与10mg/kg抗抑郁药物氟西汀效果相当。乳酸乳球菌Lactococcus lactis WHH2078能够有效缓解抑郁/焦虑样行为。
作为优选，所述乳酸乳球菌Lactococcus lactis WHH2078的服用剂量在1×109CFU/d时，中枢5-羟色胺水平上升40.47％至正常水平，BDNF水平上调124.84％至正常水平。乳酸乳球菌Lactococcus lactis WHH2078主要通过回调体内抑郁相关神经因子缓解抑郁/焦虑样行为，能够有效提高中枢神经5-羟色胺和脑源神经营养因子BDNF水平。
作为优选，所述乳酸乳球菌Lactococcus lactis WHH2078的服用剂量在1×109CFU/d时，血清皮质酮水平降低29.87％至正常水平。乳酸乳球菌Lactococcus lactisWHH2078能够有效下调血清皮质酮水平。
一种具有改善抑郁功效的乳酸乳球菌的突变体，所述突变体为对所述乳酸乳球菌进行诱变、驯化、基因重组或者经自然突变而获得的突变体。
一种具有改善抑郁功效的乳酸乳球菌及其突变体的菌体培养物，所述菌体培养物为菌液或菌剂。
一种具有改善抑郁功效的乳酸乳球菌及其突变体、菌体培养物在制备预防和/或治疗抑郁的药品、保健品或食品中的应用。
本发明提供了一种组合物，所述组合物含有所述乳酸乳球菌和/或所述突变体和/或所述菌体培养物，以及含有生理上可接受的赋形剂和/或稀释剂。
作为优选，所述赋形剂和/或稀释剂为食品、药品或保健品。
作为优选，所述食品为发酵乳、乳酪、含乳饮料、乳粉或发酵果蔬。本发明的乳酸乳球菌Lactococcus lactis WHH2078发酵特性优良，可广泛应用于食品中。
作为优选，所述药品和保健品为胶囊、粉剂或片剂。
所述组合物为口服形式并用于改善抑郁、缓解焦虑。
因此，本发明具有如下有益效果：
(1)本发明所提供的乳酸乳球菌Lactococcus lactis WHH2078具备良好的黏附特性、耐酸耐胆盐特性和肠道屏障保护功能，能够显著下调血清皮质酮水平，通过回调体内抑郁相关神经因子缓解抑郁/焦虑样行为，具有显著的改善抑郁功效；
(2)本发明的乳酸乳球菌Lactococcus lactis WHH2078发酵特性优良，可应用于发酵乳中，也可用于预防和/或治疗抑郁的药品、保健品或食品中。
附图说明
图1为本发明菌株的菌落特征(左图)和革兰氏染色显微镜观察特征(右图)。
图2为本发明菌株的生长曲线图。
图3为本发明菌株的黏附试验镜检结果图。其中，左图为对照商业菌株LGG的黏附试验镜检结果图，右图为本发明菌株乳酸乳球菌WHH2078的黏附试验镜检结果图。
图4为本发明菌株的肠道屏障电阻值动态结果图。*：表示与LGG组相比，差异显著，P<0.05；**：表示与LGG组相比，差异极显著，P<0.01；***：表示与LGG组相比，差异极显著，P<0.001。
图5为本发明菌株的旷场试验小鼠轨迹图。
图6为乳酸乳球菌WHH2078发酵乳破乳前状态。
具体实施方式
下面通过具体实施例，并结合附图，对本发明的技术方案作进一步具体的说明。
在本发明中，若非特指，所有设备和原料均可从市场购得或是本行业常用的，下述实施例中的方法，如无特别说明，均为本领域常规方法。
实施例1：乳酸乳球菌WHH2078的生物学特性
本发明所提供的菌株乳酸乳球菌WHH2078经鉴定属于乳酸乳球菌(Lactobacillushelveticus)，命名为乳酸乳球菌Lactococcus lactis，于2021年2月25日在中国微生物菌种保藏管理委员会普通微生物中心保藏，中国北京市朝阳区北辰西路1号院3号，微生物保藏编号为CGMCC NO.21831。
本发明所提供的菌株乳酸乳球菌WHH2078是从我国西藏自治区日喀则市乡村采集的酸奶酥油中分离得到。
本发明菌株乳酸乳球菌WHH2078的生物学性质如下：
形态学特征：在M17琼脂培养基中生长形态为乳白色菌落，不透明、圆形、表面光滑湿润、边缘整齐、中央凸起。革兰氏染色呈典型阳性，显微镜下观察细胞呈球状，无鞭毛，不产芽孢，不运动(图1所示)。
培养特征：最适生长温度为37℃，兼性厌氧，生长于M17培养基中。
生理特征：使用API 50CHL系统。表1中列出了本发明菌株乳酸乳球菌WHH2078的API 50CHL测试的结果。
表1.API 50结果
| 甘露醇 | ─ | 甲基-αD-吡喃葡萄糖苷 | ─ | D-来苏糖 | ─ |
| 赤藻糖醇 | ─ | N-乙酰葡萄糖胺 | + | D-塔格糖 | ─ |
| D-阿拉伯糖 | ─ | 苦杏仁苷 | ─ | D-岩藻糖 | ─ |
| L-阿拉伯糖 | ─ | ARBULIN | + | L-岩藻糖 | ─ |
| D-核糖 | + | 七叶灵柠檬酸铁 | ─ | D-阿拉伯醇 | ─ |
| D-木糖 | + | 水杨苷 | + | L-阿拉伯醇 | ─ |
| L-木糖 | ─ | D-纤维二糖 | + | 葡萄糖酸钾 | ─ |
| D-侧金盏花醇I | ─ | D-麦芽糖 | + | 2酮基葡萄糖酸钾 | ─ |
| 甲基-βD吡喃木糖苷 | ─ | D-乳糖 | + | 5酮基葡萄糖酸钾 | ─ |
| D-半乳糖 | ─ | D-密二糖 | ─ | 肌醇 | ─ |
| D-葡萄糖 | + | D-蔗糖 | ─ | 甘露醇 | + |
| D-果糖 | + | D-海藻糖 | + | 山梨醇 | ─ |
| D-甘露糖 | + | 菊粉 | ─ | 甲基-αD-吡喃甘露糖苷 | ─ |
| L-山梨糖 | ─ | D-松三糖 | ─ | 糖原 | ─ |
| L-鼠李糖 | ─ | D-棉子糖 | ─ | 木糖醇 | ─ |
| 卫茅醇 | ─ | 淀粉 | ─ | D-龙胆二糖 | + |
| D-土伦糖 | ─ |
生物学鉴定：针对16S rRNA基因序列测序，所得结果于NCBI的GenBank数据库中进行同源性比对分析，结果显示该菌株为乳酸乳球菌(Lactococcus lactis)，16S rRNA基因序列已上传至GenBank数据库(登陆号：MW805736)。
实施例2乳酸乳球菌WHH2078的培养
本发明菌株乳酸乳球菌WHH2078经二代活化后，按1％接种量接种于M17培养基中，在37℃温度下培养24h，每隔1h取样一次，测定其在600nm波长的光密度(OD)值，绘制生长曲线，设置三次重复。
结果如图2所示，乳酸乳球菌WHH2078在经过0-2h的生长迟缓期后，从2h开始快速生长进入对数生长期，6h结束对数期进入稳定期。
实施例3乳酸乳球菌WHH2078的耐酸耐胆盐性能
本发明菌株乳酸乳球菌WHH2078、商业菌株鼠李糖乳杆菌GG(LGG)经二代活化后，取对数生长末期菌液，4000rpm离心10min，弃上清，收集菌泥，分别进行如下操作：①分别加入相同体积pH 2.5、3.0和3.5的M17培养液，吹打混匀后，在37℃环境下孵育，用稀释涂布计数法测定0点及孵育3h后菌数的变化；②分别加入相同体积的含有0.1％、0.2％和0.3％胆盐的M17培养液，吹打混匀后，在37℃环境下孵育，用稀释涂布计数法测定0h及孵育8h后菌数的变化。菌株存活率计算公式：
菌株存活率(％)＝N1/N0×100％
N1为菌株孵育后活菌数的log10值，N0为菌株初始活菌数的log10值。
结果如表2所示，本发明菌株具有良好的耐受特性。在pH 3.5环境下孵育3h存活率为66.67％，在pH 3.0环境下孵育3h存活率为54.07％，在pH 2.5环境下孵育3h存活率仍有42.67％，表明本发明菌株具有良好的耐酸性能。
本发明菌株在0.1％胆盐浓度下孵育8h存活率为64.33％，在0.2％胆盐浓度下孵育8h存活率为51.91％，在0.3％胆盐浓度下孵育8h存活率仍有38.11％，表明本发明菌株具有良好的耐胆盐特性。
表2.耐受性结果
-：未检测到。
实施例4乳酸乳球菌WHH2078的黏附性
建立HT-29细胞培养体系，细胞生长于含10％胎牛血清的DMEM培养基中(含青霉素100U/mL，链霉素100mg/mL)。待细胞传至第三代，采用0.25％的胰酶(含EDTA)消化，获得单细胞悬液，细胞以1×106细胞/孔的密度接种于已放置细胞爬片的12孔细胞培养板中，于37℃，5％CO2培养箱中培养2d。
本发明菌株乳酸乳球菌WHH2078和对照商业菌株鼠李糖乳杆菌GG(LGG)经二代活化后，取对数生长末期菌液，4000rpm离心10min，弃上清，获得菌泥，重悬于含10％胎牛血清的DMEM完全培养基(不加双抗)中，取1×108CFU/mL的菌液1mL接种于上述12孔细胞培养板中，37℃下于5％CO2培养箱中孵育2h。孵育结束后，缓慢吸去培养液，用PBS洗涤3次，用100％甲醇固定8min。取出细胞爬片静置20min，经革兰氏染色后，用中性树脂封片。于光学显微镜下进行观察，设置三次重复，每个片子随机选取10个视野计数。
结果如表3和图3所示，乳酸乳球菌WHH2078的单细胞黏附数高达10.33±1.10，显著优于对照商业菌株LGG(3.80±0.40)。
表3.黏附性结果
| 菌株编号 | 黏附率(菌数/细胞数) |
| LGG | 3.80±0.40 |
| WHH2078 | 10.33±1.10*** |
与对照商业菌株相比，***：差异极显著，P<0.001。
实施例5乳酸乳球菌WHH2078的肠道屏障保护功能
建立IPEC-J2细胞培养体系，细胞生长于含10％胎牛血清的DMEM培养基中(含青霉素100U/mL，链霉素100mg/mL)。待细胞传至第三代，采用0.25％的胰酶(含EDTA)消化，获得单细胞悬液，细胞以1×106细胞/孔的密度接种于24孔Transwell细胞(小室孔径0.4μm)培养板中，于37℃，5％CO2培养箱中培养7d。
本发明菌株乳酸乳球菌WHH2078和对照商业菌株鼠李糖乳杆菌GG(LGG)经二代活化后，取对数生长末期菌液，4000rpm离心10min，弃上清，获得菌泥，重悬于含10％胎牛血清的DMEM完全培养基(不加双抗)中，取1×108CFU/mL的菌液1mL接种于上述24孔Transwell小室内(呈上下、左右轻微振荡混匀)，37℃下于5％CO2培养箱中孵育12h。试验于0、2、4、6、8、10和12h分别将Transwell细胞板取出，采用Millicell ERS-2电阻仪对不同细菌处理后肠道屏障小室的电阻值进行检测，试验设置三次重复。根据公式，随后对电阻值进行数据统计统计。
电阻值TEER计算公式：
TEER＝(电阻值-空白电阻值)×膜面积
TEER变化率(％)＝(TEER/初始TEER)×100-100
结果如图4所示，乳酸乳球菌WHH2078在孵育12h的肠道屏障电阻值增加89.76％±1.03％，显著优于对照商业菌株LGG(70.12％±3.12％)。
实施例6乳酸乳球菌WHH2078的改善抑郁功效
本发明采用健康的SPF级雄性BALB/c小鼠(4-5周龄，22±0.2g)，建立慢性不可预见性温和抑郁小鼠模型(CUMS)。同时每天灌胃乳酸乳球菌WHH2078菌株，活菌数1×109CFU/mL，试验为期32天，最后检测抑郁小鼠抑郁/焦虑样行为、脑部5-羟色胺和BDNF水平，以及血清皮质酮水平，来判断该菌株是否具有改善抑郁的功效。
小鼠饲养于室温26±0.5℃、湿度50-60％、昼夜明暗交替时间(12/12h)的洁净环境中。饲养期间，小鼠可自由采食和饮水。CUMS小鼠致郁项目包括：束缚6h、4℃冰水游泳1min、禁食24h、禁水24h、潮湿环境24h和无垫料环境24h等，试验组小鼠每天随机进行一项项目。
小鼠随机分为4组，每组10只。分组如下：
对照组：正常小鼠，灌胃200μL无菌生理盐水
抑郁组：CUMS抑郁小鼠，灌胃200μL无菌生理盐水
药物组：CUMS抑郁小鼠，灌胃200μL无菌氟西汀液(10mg/kg/d)
WHH2078组：CUMS抑郁小鼠，灌胃200μL本发明菌株悬液(1×109CFU/d)
试验32天后，对试验小鼠进行行为学检测，通过悬尾试验和强迫游泳试验评价小鼠抑郁样行为，采用旷场试验评价小鼠的焦虑样行为。行为学检测结束后，1％戊巴比妥钠(0.5mL/100gBW)麻醉，采用心脏穿刺取血获得小鼠血液样本，将血液样本取出后，静置30min，4℃，4000rpm离心15min，取上清，用ELISA试剂盒检测血清皮质酮含量。脱颈处死后，解剖取大脑海马区组织，匀浆后用ELISA试剂盒检测海马区5-羟色胺和BDNF浓度。
试验小鼠抑郁样行为结果如表4所示，抑郁组小鼠悬尾试验不动时间和强迫游泳试验不动时间均显著高于对照组小鼠(P<0.05)，表明造模成功。乳酸乳球菌WHH2078组小鼠悬尾试验不动时间(P<0.05)和强迫游泳试验不动时间(P<0.05)均显著低于抑郁组小鼠，表明乳酸乳球菌WHH2078服用浓度在1×109CFU/d具有缓解抑郁小鼠抑郁样行为的能力。乳酸乳球菌WHH2078组小鼠悬尾试验不动时间与药物组差异不显著(P>0.05)，同时强迫游泳试验不动时间显著低于药物组(P<0.05)，表明乳酸乳球菌WHH2078服用浓度在1×109CFU/d缓解抑郁样行为的功效与药物氟西汀(10mg/kg)相当。
试验小鼠焦虑样行为结果如表4和图5所示，乳酸乳球菌WHH2078组小鼠旷场试验中央探索时间显著高于抑郁组小鼠(P<0.05)，表明乳酸乳球菌WHH2078服用浓度在1×109CFU/d具有缓解抑郁小鼠焦虑样行为的能力。同时，与药物组无显著差异(P>0.05)，说明乳酸乳球菌WHH2078服用浓度在1×109CFU/d缓解焦虑样行为的功能与药物氟西汀(10mg/kg)相当。
表4.小鼠行为学结果
a，b，c，d：差异显著，P<0.05。
试验小鼠脑海马区5-羟色胺水平如表5所示，抑郁组小鼠脑海马区5-羟色胺浓度显著低于对照组小鼠(P<0.05)，表明造模成功。乳酸乳球菌WHH2078组小鼠脑海马区5-羟色胺浓度显著高于抑郁组小鼠(P<0.05)，与对照组小鼠差异不显著(P>0.05)，表明乳酸乳球菌WHH2078服用浓度在1×109CFU/d具有上调抑郁小鼠脑海马区5-羟色胺水平的能力。同时，与药物组无显著差异(P>0.05)，说明乳酸乳球菌WHH2078服用浓度在1×109CFU/d对脑海马区5-羟色胺水平的调节能力与药物氟西汀(10mg/kg)相似。
试验小鼠脑海马区BDNF水平如表5所示，抑郁组小鼠脑海马区BDNF浓度显著低于对照组小鼠(P<0.05)，表明造模成功。乳酸乳球菌WHH2078组小鼠脑海马区BDNF浓度显著高于抑郁组小鼠(P<0.05)，与对照组小鼠差异不显著(P>0.05)，表明乳酸乳球菌WHH2078服用浓度在1×109CFU/d具有上调抑郁小鼠脑海马区BDNF水平的能力。同时，与药物组无显著差异(P>0.05)，说明乳酸乳球菌WHH2078服用浓度在1×109CFU/d对脑海马区BDNF水平的调节能力与药物氟西汀(10mg/kg)相当。
试验小鼠血清皮质酮水平如表5所示，抑郁组小鼠血清皮质酮浓度显著高于对照组小鼠(P<0.05)，表明造模成功。乳酸乳球菌WHH2078组小鼠血清皮质酮浓度显著低于抑郁组小鼠(P<0.05)，表明乳酸乳球菌WHH2078服用浓度在1×109CFU/d具有回调抑郁小鼠血清皮质酮浓度水平的能力。
表5.小鼠抑郁相关生物学指标结果
a，b：差异显著，P<0.05。
总之，乳酸乳球菌1889菌株服用浓度在1×109CFU/d能够显著缓解抑郁/焦虑样行为，回调脑海马区5-羟色胺、BDNF和血液皮质酮水平，是一株具有改善抑郁功能的新菌株。
应用实施例
实施例1乳酸乳球菌WHH2078冻干菌粉的制作
本发明菌株乳酸乳球菌WHH2078以1％的接种量接种于10ml液体M17培养基中，在37℃恒温培养箱中培养6h(一代种子液)，以此传至两代。二代种子1％的接种量接种于10L含有液体M17培养基的发酵罐中，37℃培养6h，收集菌液，8000rpm离心10min收集菌体，用0.9％生理盐水洗涤一次，加入四倍菌泥量的含有脱脂乳粉、葡萄糖、甘油的保护剂中重悬，真空冷冻干燥，菌粉真空包装。制得的菌粉活菌数可达2×1011CFU/g，可用于含有乳酸乳球菌WHH2078的具有改善抑郁功能相关药品、保健品、食品、饮料或发酵剂产品的制作和生产。
实施例2乳酸乳球菌WHH2078发酵乳的制作
准确称取脱脂乳100g，45-50℃纯净水900g，50℃温水溶解，剪切20min，50℃水化30min，均质，95℃杀菌5min。降温后，按1％接种量接入应用实施例1中的乳酸乳球菌WHH2078发酵剂，37℃发酵12h，4℃后熟12h。观察其凝乳状态，用打蛋器破乳后，检测其拉丝长度、pH、酸度、黏度和活菌数，设置三次重复。
结果如图6和表6所示，发酵乳凝乳状态紧实，表面光滑，有少量清洗出，破乳后，经较长时间搅拌丝滑粘稠，无拉丝，活菌数达1.15×109CFU/mL，感官和风味良好，奶香浓郁，口感细腻丝滑，该发酵乳即为含有乳酸乳球菌WHH2078的具有改善抑郁功能的发酵乳。
表6.乳酸乳球菌WHH2078发酵乳特性
| pH | 酸度(°T) | 黏度(cp) | 活菌数(CFU/mL) |
| 4.76±0.02 | 78±0.59 | 3082±5.54 | 1.15×109 |
以上所述仅为本发明的较佳实施例，并非对本发明作任何形式上的限制，在不超出权利要求所记载的技术方案的前提下还有其它的变体及改型。
Claims (3)
1.一株具有改善抑郁功效的乳酸乳球菌，其特征在于，命名为乳酸乳球菌WHH2078（Lactococcus lactis），该菌株已于2021年2月25日保藏于中国微生物菌种保藏管理委员会普通微生物中心，其保藏编号为CGMCC NO.21831。
2.一种如权利要求1所述的具有改善抑郁功效的乳酸乳球菌的菌体培养物，其特征在于，所述菌体培养物为菌液或菌剂。
3.一种如权利要求1所述的具有改善抑郁功效的乳酸乳球菌及菌体培养物在制备预防和/或治疗抑郁的药品中的应用。
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