益生菌在免疫、代谢及神经情绪失调预防和治疗方面的功能活性及机制研究进展
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摘要
对益生菌功能活性的研究已经拓展到免疫、代谢及神经情绪疾病的预防和治疗方面,而在这些方面的众多研究却缺乏系统总结。本文针对乳杆菌和双歧杆菌两类主要的益生菌在相关领域的动物活性、临床实验及作用机制研究进展进行总结。众多研究表明,益生菌作为功能性成分用于食品开发中将为国民身体健康及生活质量的进一步改善提供助力。深入研究人体病症和益生菌相互作用的机制,特别是人体对不同菌株的响应机理,以开发可用于临床治疗的菌株,是未来益生菌研究的重要方向。
While research on the functional effects of probiotics has been extended to include their roles in prevention and treatment of immune, metabolic and neuroemotional disorders, a systematic review of the numerous studies in this regard is still lacking in the literature. In this paper, we summarize recent animal and clinical studies on the two probiotics, Lactobacillus and Bifidobacterium and recent studies on their mechanism of action. A number of studies demonstrate that the application of probiotics as a functional food ingredient will help further improve people's health and living standard. The mechanism of action of probiotics on human diseases and disorders especially the body's responses to different probiotics, which allows the development of therapeutic strains for clinical applications, will represent an important direction of research in the future.
While research on the functional effects of probiotics has been extended to include their roles in prevention and treatment of immune, metabolic and neuroemotional disorders, a systematic review of the numerous studies in this regard is still lacking in the literature. In this paper, we summarize recent animal and clinical studies on the two probiotics, Lactobacillus and Bifidobacterium and recent studies on their mechanism of action. A number of studies demonstrate that the application of probiotics as a functional food ingredient will help further improve people's health and living standard. The mechanism of action of probiotics on human diseases and disorders especially the body's responses to different probiotics, which allows the development of therapeutic strains for clinical applications, will represent an important direction of research in the future.
引文
[1] LIANG Shi, WANG Tian, HU Xia, et al. Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive,and biochemical aberrations caused by chronic restraint stress[J]. Neuroscience, 2015, 310:561-577. DOI:10.1016/j.neuroscience.2015.09.033.
[2] REIS D J, ILARDI S S, PUNT S E W. The anxiolytic effect of probiotics:a systematic review and meta-analysis of the clinical and preclinical literature[J]. PLoS One, 2018, 13(6):e0199041.DOI:10.1371/journal.pone.0199041.
[3] YAMASHITA M, UKIBE K, MATSUBARA Y, et al. Lactobacillus helveticus SBT2171 attenuates experimental autoimmune encephalomyelitis in mice[J]. Frontiers in Microbiology, 2017, 8:2596-2606. DOI:10.3389/fmicb.2017.02596.
[4] GOHIL P, PATEL V, DESHPANDE S, et al. Anti-arthritic activity of cell wall content of Lactobacillus plantarum in freund’s adjuvantinduced arthritic rats:involvement of cellular inflammatory mediators and other biomarkers[J]. Inflammopharmacology, 2018, 26(1):171-181. DOI:10.1007/s10787-017-0370-z.
[5] YAMASHITA M, MATSUMOTO K, ENDO T, et al. Preventive effect of Lactobacillus helveticus SBT2171 on collagen-induced arthritis in mice[J]. Frontiers in Microbiology, 2017, 8:1159-1171.DOI:10.3389/fmicb.2017.01159.
[6] DENNIS-WALL J C, CULPEPPER T, NIEVES C, Jr, et al. Probiotics(Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2)improve rhinoconjunctivitisspecific quality of life in individuals with seasonal allergies:a double-blind, placebo-controlled, randomized trial[J]. The American Journal of Clinical Nutrition, 2017, 105(3):758-767. DOI:10.3945/ajcn.116.140012.
[7] CHOI S P, OH H N, CHOI C Y, et al. Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 alleviates birch pollen-induced allergic rhinitis in mice[J]. Journal of Applied Microbiology, 2018, 124(3):821-828. DOI:10.1111/jam.13635.
[8]彭吉祥,王彦波,傅玲琳.双歧杆菌对中国对虾原肌球蛋白致敏小鼠的免疫调控作用[J].微生物学报, 2017, 57(7):1026-1037.DOI:10.13343/j.cnki.wsxb.20160390.
[9] FU Linglin, SONG Jinyu, WANG Chong, et al. Bifidobacterium infantis potentially alleviates shrimp tropomyosin-induced allergy by tolerogenic dendritic cell-dependent induction of regulatory T cells and alterations in gut microbiota[J]. Frontiers in Immunology, 2017, 8:1536-1550. DOI:10.3389/fimmu.2017.01536.
[10]MCCARVILLE J L, DONG J, CAMINERO A, et al.A commensal Bifidobacterium longum strain improves gluten-related immunopathology in mice through expression of a serine protease inhibitor[J]. Applied and Environmental Microbiology, 2017, 83(19):1323-1336. DOI:10.1128/AEM.01323-17.
[11] PARVANEH M, KARIMI G, JAMALUDDIN R, et al. Lactobacillus helveticus(ATCC 27558)upregulates Runx2 and Bmp2 and modulates bone mineral density in ovariectomy-induced bone loss rats[J].Clinical Interventions in Aging, 2018, 13:1555-1564. DOI:10.2147/CIA.S169223.
[12] DAR H Y, SHUKLA P, MISHRA P K, et al. Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in osteoporotic mice via modulating Treg-Th17 cell balance[J]. Bone Reports, 2018, 8:46-56. DOI:10.1016/j.bonr.2018.02.001.
[13] GIRI S S, YUN S, JUN J W, et al. Therapeutic effect of intestinal autochthonous Lactobacillus reuteri P16 against waterborne lead toxicity in Cyprinus carpio[J]. Frontiers in Immunology, 2018, 9:1824-1837. DOI:10.3389/fimmu.2018.01824.
[14] KANO H, YAMADA N, SAITO C, et al. Lactobacillus gasseri PA-3,but not L. gasseri OLL2996, reduces the absorption of purine nucleosides in rats[J]. Nucleosides, Nucleotides and Nucleic Acids,2018, 37(6):353-360. DOI:10.1080/15257770.2018.1469760.
[15] YAMANAKA H, TANIGUCHI A, TSUBOI H, et al. Hypouricaemic effects of yoghurt containing Lactobacillus gasseri PA-3 in patients with hyperuricaemia and/or gout:a randomised, double-blind,placebo-controlled study[J]. Modern Rheumatology, 2019, 37(1):146-150. DOI:10.1080/14397595.2018.1442183.
[16] YAMADA N, SAITO C, MURAYAMA-CHIBA Y, et al.Lactobacillus gasseri PA-3 utilizes the purines GMP and guanosine and decreases their absorption in rats[J]. Nucleosides, Nucleotides and Nucleic Acids, 2018, 37(5):307-315. DOI:10.1080/15257770.2018.1454949.
[17] LI Xiuxiang, SONG Yong, MA Xiuyan, et al. Lactobacillus plantarum and Lactobacillus fermentum alone or in combination regulate intestinal flora composition and systemic immunity to alleviate obesity syndrome in high-fat diet rat[J]. International Journal of Food Science and Technology, 2018, 53(1):137-146. DOI:10.1111/ijfs.13567.
[18] BAUER P V, DUCA F A, WAISE T M Z, et al. Lactobacillus gasseri in the upper small intestine impacts an ACSL3-dependent fatty acidsensing pathway regulating whole-body glucose homeostasis[J]. Cell Metabolism, 2018, 27(3):572-587. DOI:10.1016/j.cmet.2018.01.013.
[19] JI Y, PARK S, PARK H, et al. Modulation of active gut microbiota by Lactobacillus rhamnosus GG in a diet induced obesity murine model[J]. Frontiers in Microbiology, 2018, 9:710-723. DOI:10.3389/fmicb.2018.00710.
[20] SKRZYPCZAK K, GUSTAW W, SZWAJGIER D, et al. Kappacasein as a source of short-chain bioactive peptides generated by Lactobacillus helveticus[J]. Journal of Food Science and Technology,2017, 54(11):3679-3688. DOI:10.1007/s13197-017-2830-2.
[21] CHEN Li, ZHANG Qiuhong, JI Zhe, et al. Production and fermentation characteristics of angiotensin-I-converting enzyme inhibitory peptides of goat milk fermented by a novel wild Lactobacillus plantarum 69[J].LWT-Food Science and Technology, 2018, 91:532-540. DOI:10.1016/j.lwt.2018.02.002.
[22] LI Chuan, CAO Jun, NIE Shaoping, et al. Serum metabolomics analysis for biomarker of Lactobacillus plantarum NCU116 on hyperlipidaemic rat model feed by high fat diet[J]. Journal of Functional Foods, 2018, 42:171-176. DOI:10.1016/j.jff.2017.12.036.
[23] AMINLARI L, SHEKARFOROUSH S, HOSSEINZADEH S, et al.Effect of probiotics Bacillus coagulans and Lactobacillus plantarum on lipid profile and feces bacteria of rats fed cholesterol enriched diet[J]. Probiotics and Antimicrobial Proteins, 2018, 10(5):1-9.DOI:10.1007/s12602-018-9480-1.
[24] MATSUMOTO M, KITA DA Y, SHIMOMURA Y, et al.Bifidobacterium animalis subsp. lactis LKM512 reduces levels of intestinal trimethylamine produced by intestinal microbiota in healthy volunteers:a double-blind, placebo-controlled study[J]. Journal of Functional Foods, 2017, 36:94-101. DOI:10.1016/j.jff.2017.06.032.
[25] KLING D N, DEBOSE-SCARLETT E M, TEIXEIRA L D, et al. Sex modulates Lactobacillus johnsonii N6.2 and phytophenol effectiveness in reducing high fat diet induced mTOR activation in sprague-dawley rats[J]. Frontiers in Microbiology, 2018, 9:2649-2665. DOI:10.3389/fmicb.2018.02649.
[26] GAO He, WEN Jiajia, HU Jielun, et al. Polysaccharide from fermented Momordica charantia L. with Lactobacillus plantarum NCU116ameliorates type 2 diabetes in rats[J]. Carbohydrate Polymers, 2018,201:624-633. DOI:10.1016/j.carbpol.2018.08.075.
[27] CHAIYASUT C, WORAHARN S, SIVAMARUTHI B S, et al.Lactobacillus fermentum HP3-mediated fermented hericium erinaceus juice as a health promoting food supplement to manage diabetes mellitus[J]. Journal of Evidence-Based Integrative Medicine, 2018, 23:2515690X18765699. DOI:10.1177/2515690X18765699.
[28] KOBAYASHI Y, SUGAHARA H, SHIMADA K, et al. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease[J]. Scientific Reports, 2017, 7(1):13510-13520. DOI:10.1038/s41598-017-13368-2.
[29] LIM S M, JANG H M, JEONG J J, et al. Lactobacillus johnsonii CJLJ103 attenuates colitis and memory impairment in mice by inhibiting gut microbiota lipopolysaccharide production and NF-κB activation[J]. Journal of Functional Foods, 2017, 34:359-368.DOI:10.1016/j.jff.2017.05.016.
[30] OHSAWA K, NAKAMURA F, UCHIDA N, et al. Lactobacillus helveticus-fermented milk containing lactononadecapeptide(NIPPLTQTPVVVPPFLQPE)improves cognitive function in healthy middle-aged adults:a randomised, double-blind, placebo-controlled trial[J]. International Journal of Food Sciences and Nutrition, 2018,69(3):369-376. DOI:10.1080/09637486.2017.1365824.
[31] LIU W H, CHUANG H L, HUANG Y T, et al. Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice[J]. Behavioural Brain Research, 2016, 298:202-209. DOI:10.1016/j.bbr.2015.10.046.
[32] BHARWANI A, MIAN M F, SURETTE M G, et al. Oral treatment with Lactobacillus rhamnosus attenuates behavioural deficits and immune changes in chronic social stress[J]. BMC Medicine, 2017,15(7):1-14. DOI:10.1186/s12916-016-0771-7.
[33] NISHIDA K, SAWADA D, KUWANO Y, et al. Daily administration of paraprobiotic Lactobacillus gasseri CP2305 ameliorates chronic stress-associated symptoms in Japanese medical students[J]. Journal of Functional Foods, 2017, 36:112-121. DOI:10.1016/j.jff.2017.06.031.
[2] REIS D J, ILARDI S S, PUNT S E W. The anxiolytic effect of probiotics:a systematic review and meta-analysis of the clinical and preclinical literature[J]. PLoS One, 2018, 13(6):e0199041.DOI:10.1371/journal.pone.0199041.
[3] YAMASHITA M, UKIBE K, MATSUBARA Y, et al. Lactobacillus helveticus SBT2171 attenuates experimental autoimmune encephalomyelitis in mice[J]. Frontiers in Microbiology, 2017, 8:2596-2606. DOI:10.3389/fmicb.2017.02596.
[4] GOHIL P, PATEL V, DESHPANDE S, et al. Anti-arthritic activity of cell wall content of Lactobacillus plantarum in freund’s adjuvantinduced arthritic rats:involvement of cellular inflammatory mediators and other biomarkers[J]. Inflammopharmacology, 2018, 26(1):171-181. DOI:10.1007/s10787-017-0370-z.
[5] YAMASHITA M, MATSUMOTO K, ENDO T, et al. Preventive effect of Lactobacillus helveticus SBT2171 on collagen-induced arthritis in mice[J]. Frontiers in Microbiology, 2017, 8:1159-1171.DOI:10.3389/fmicb.2017.01159.
[6] DENNIS-WALL J C, CULPEPPER T, NIEVES C, Jr, et al. Probiotics(Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2)improve rhinoconjunctivitisspecific quality of life in individuals with seasonal allergies:a double-blind, placebo-controlled, randomized trial[J]. The American Journal of Clinical Nutrition, 2017, 105(3):758-767. DOI:10.3945/ajcn.116.140012.
[7] CHOI S P, OH H N, CHOI C Y, et al. Oral administration of Lactobacillus plantarum CJLP133 and CJLP243 alleviates birch pollen-induced allergic rhinitis in mice[J]. Journal of Applied Microbiology, 2018, 124(3):821-828. DOI:10.1111/jam.13635.
[8]彭吉祥,王彦波,傅玲琳.双歧杆菌对中国对虾原肌球蛋白致敏小鼠的免疫调控作用[J].微生物学报, 2017, 57(7):1026-1037.DOI:10.13343/j.cnki.wsxb.20160390.
[9] FU Linglin, SONG Jinyu, WANG Chong, et al. Bifidobacterium infantis potentially alleviates shrimp tropomyosin-induced allergy by tolerogenic dendritic cell-dependent induction of regulatory T cells and alterations in gut microbiota[J]. Frontiers in Immunology, 2017, 8:1536-1550. DOI:10.3389/fimmu.2017.01536.
[10]MCCARVILLE J L, DONG J, CAMINERO A, et al.A commensal Bifidobacterium longum strain improves gluten-related immunopathology in mice through expression of a serine protease inhibitor[J]. Applied and Environmental Microbiology, 2017, 83(19):1323-1336. DOI:10.1128/AEM.01323-17.
[11] PARVANEH M, KARIMI G, JAMALUDDIN R, et al. Lactobacillus helveticus(ATCC 27558)upregulates Runx2 and Bmp2 and modulates bone mineral density in ovariectomy-induced bone loss rats[J].Clinical Interventions in Aging, 2018, 13:1555-1564. DOI:10.2147/CIA.S169223.
[12] DAR H Y, SHUKLA P, MISHRA P K, et al. Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in osteoporotic mice via modulating Treg-Th17 cell balance[J]. Bone Reports, 2018, 8:46-56. DOI:10.1016/j.bonr.2018.02.001.
[13] GIRI S S, YUN S, JUN J W, et al. Therapeutic effect of intestinal autochthonous Lactobacillus reuteri P16 against waterborne lead toxicity in Cyprinus carpio[J]. Frontiers in Immunology, 2018, 9:1824-1837. DOI:10.3389/fimmu.2018.01824.
[14] KANO H, YAMADA N, SAITO C, et al. Lactobacillus gasseri PA-3,but not L. gasseri OLL2996, reduces the absorption of purine nucleosides in rats[J]. Nucleosides, Nucleotides and Nucleic Acids,2018, 37(6):353-360. DOI:10.1080/15257770.2018.1469760.
[15] YAMANAKA H, TANIGUCHI A, TSUBOI H, et al. Hypouricaemic effects of yoghurt containing Lactobacillus gasseri PA-3 in patients with hyperuricaemia and/or gout:a randomised, double-blind,placebo-controlled study[J]. Modern Rheumatology, 2019, 37(1):146-150. DOI:10.1080/14397595.2018.1442183.
[16] YAMADA N, SAITO C, MURAYAMA-CHIBA Y, et al.Lactobacillus gasseri PA-3 utilizes the purines GMP and guanosine and decreases their absorption in rats[J]. Nucleosides, Nucleotides and Nucleic Acids, 2018, 37(5):307-315. DOI:10.1080/15257770.2018.1454949.
[17] LI Xiuxiang, SONG Yong, MA Xiuyan, et al. Lactobacillus plantarum and Lactobacillus fermentum alone or in combination regulate intestinal flora composition and systemic immunity to alleviate obesity syndrome in high-fat diet rat[J]. International Journal of Food Science and Technology, 2018, 53(1):137-146. DOI:10.1111/ijfs.13567.
[18] BAUER P V, DUCA F A, WAISE T M Z, et al. Lactobacillus gasseri in the upper small intestine impacts an ACSL3-dependent fatty acidsensing pathway regulating whole-body glucose homeostasis[J]. Cell Metabolism, 2018, 27(3):572-587. DOI:10.1016/j.cmet.2018.01.013.
[19] JI Y, PARK S, PARK H, et al. Modulation of active gut microbiota by Lactobacillus rhamnosus GG in a diet induced obesity murine model[J]. Frontiers in Microbiology, 2018, 9:710-723. DOI:10.3389/fmicb.2018.00710.
[20] SKRZYPCZAK K, GUSTAW W, SZWAJGIER D, et al. Kappacasein as a source of short-chain bioactive peptides generated by Lactobacillus helveticus[J]. Journal of Food Science and Technology,2017, 54(11):3679-3688. DOI:10.1007/s13197-017-2830-2.
[21] CHEN Li, ZHANG Qiuhong, JI Zhe, et al. Production and fermentation characteristics of angiotensin-I-converting enzyme inhibitory peptides of goat milk fermented by a novel wild Lactobacillus plantarum 69[J].LWT-Food Science and Technology, 2018, 91:532-540. DOI:10.1016/j.lwt.2018.02.002.
[22] LI Chuan, CAO Jun, NIE Shaoping, et al. Serum metabolomics analysis for biomarker of Lactobacillus plantarum NCU116 on hyperlipidaemic rat model feed by high fat diet[J]. Journal of Functional Foods, 2018, 42:171-176. DOI:10.1016/j.jff.2017.12.036.
[23] AMINLARI L, SHEKARFOROUSH S, HOSSEINZADEH S, et al.Effect of probiotics Bacillus coagulans and Lactobacillus plantarum on lipid profile and feces bacteria of rats fed cholesterol enriched diet[J]. Probiotics and Antimicrobial Proteins, 2018, 10(5):1-9.DOI:10.1007/s12602-018-9480-1.
[24] MATSUMOTO M, KITA DA Y, SHIMOMURA Y, et al.Bifidobacterium animalis subsp. lactis LKM512 reduces levels of intestinal trimethylamine produced by intestinal microbiota in healthy volunteers:a double-blind, placebo-controlled study[J]. Journal of Functional Foods, 2017, 36:94-101. DOI:10.1016/j.jff.2017.06.032.
[25] KLING D N, DEBOSE-SCARLETT E M, TEIXEIRA L D, et al. Sex modulates Lactobacillus johnsonii N6.2 and phytophenol effectiveness in reducing high fat diet induced mTOR activation in sprague-dawley rats[J]. Frontiers in Microbiology, 2018, 9:2649-2665. DOI:10.3389/fmicb.2018.02649.
[26] GAO He, WEN Jiajia, HU Jielun, et al. Polysaccharide from fermented Momordica charantia L. with Lactobacillus plantarum NCU116ameliorates type 2 diabetes in rats[J]. Carbohydrate Polymers, 2018,201:624-633. DOI:10.1016/j.carbpol.2018.08.075.
[27] CHAIYASUT C, WORAHARN S, SIVAMARUTHI B S, et al.Lactobacillus fermentum HP3-mediated fermented hericium erinaceus juice as a health promoting food supplement to manage diabetes mellitus[J]. Journal of Evidence-Based Integrative Medicine, 2018, 23:2515690X18765699. DOI:10.1177/2515690X18765699.
[28] KOBAYASHI Y, SUGAHARA H, SHIMADA K, et al. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer’s disease[J]. Scientific Reports, 2017, 7(1):13510-13520. DOI:10.1038/s41598-017-13368-2.
[29] LIM S M, JANG H M, JEONG J J, et al. Lactobacillus johnsonii CJLJ103 attenuates colitis and memory impairment in mice by inhibiting gut microbiota lipopolysaccharide production and NF-κB activation[J]. Journal of Functional Foods, 2017, 34:359-368.DOI:10.1016/j.jff.2017.05.016.
[30] OHSAWA K, NAKAMURA F, UCHIDA N, et al. Lactobacillus helveticus-fermented milk containing lactononadecapeptide(NIPPLTQTPVVVPPFLQPE)improves cognitive function in healthy middle-aged adults:a randomised, double-blind, placebo-controlled trial[J]. International Journal of Food Sciences and Nutrition, 2018,69(3):369-376. DOI:10.1080/09637486.2017.1365824.
[31] LIU W H, CHUANG H L, HUANG Y T, et al. Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice[J]. Behavioural Brain Research, 2016, 298:202-209. DOI:10.1016/j.bbr.2015.10.046.
[32] BHARWANI A, MIAN M F, SURETTE M G, et al. Oral treatment with Lactobacillus rhamnosus attenuates behavioural deficits and immune changes in chronic social stress[J]. BMC Medicine, 2017,15(7):1-14. DOI:10.1186/s12916-016-0771-7.
[33] NISHIDA K, SAWADA D, KUWANO Y, et al. Daily administration of paraprobiotic Lactobacillus gasseri CP2305 ameliorates chronic stress-associated symptoms in Japanese medical students[J]. Journal of Functional Foods, 2017, 36:112-121. DOI:10.1016/j.jff.2017.06.031.