Modulatory effects of <i>Lactiplantibacillus plantarum</i> on chronic metabolic diseases

Lei Tian; Ruixiang Zhao; Xinyi Xu; Zhiwei Zhou; Xiaofang Xu; Dongmei Luo; Zhiqiang Zhou; Yu Liu; Ariel Kushmaro; Robert S. Marks; András Dinnyés; Qun Sun

doi:10.1016/j.fshw.2022.10.018

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Review Article | Open Access

Modulatory effects of Lactiplantibacillus plantarum on chronic metabolic diseases

Lei Tian^{^a^,¹}, Ruixiang Zhao^{^b^,¹}, Xinyi Xu^{^a}, Zhiwei Zhou^{^a}, Xiaofang Xu^{^a}, Dongmei Luo^{^a}, Zhiqiang Zhou^{^c}, Yu Liu^{^d}, Ariel Kushmaro^{^e}, Robert S. Marks^{^e}, András Dinnyés^{^a^,^f^,^g^,^h}, Qun Sun^{^a^,^c}

()

Key Laboratory of Bio-Resource and Eco-Environment of the Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, China

Institute for Marine and Antarctic Studies, University of Tasmania, Newnham 7248, Australia

College of Biomass Science and Engineering, Sichuan University, Chengdu 610064, China

Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu 610041, China

Avram and Stella Goldstein-Goren, Department of Biotechnology Engineering, Faculty of Engineering Sciences, Ben Gurion University of the Negev, Beer-Sheva 84105, Israel

BioTalentum Ltd., Gödöllő 2100, Hungary

Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged H-6270, Hungary

Hungarian University of Agriculture and Life Sciences, Institute of Physiology and Animal Nutrition, Department of Physiology and Animal Health, Gödöllő 2100, Hungary

1 These authors contributed equally to this work.Peer review under responsibility of KeAi Communications Co., Ltd.]]>

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Abstract

The increased global incidence of chronic metabolic diseases, a vital threat to human health and a burden on our healthcare systems, includes a series of clinical metabolic syndromes such as obesity, diabetes, hypertension, and dyslipidemia. One of the well-known probiotic microorganisms, Lactiplantibacillus plantarum plays an important role in promoting human health, including inhibiting the occurrence and development of a variety of chronic metabolic diseases. The present study provides an overview of the preventive and therapeutic effects of L. plantarum on diabetes, obesity, non-alcoholic fatty liver disease, kidney stone disease, and cardiovascular diseases in animal models and human clinical trials. Ingesting L. plantarum demonstrated its ability to reduce inflammatory and oxidative stress levels by regulating the production of cytokines and short-chain fatty acids (SCFAs), the activity of antioxidant enzymes, and the balance of intestinal microbial communities to alleviate the symptoms of chronic metabolic diseases. Furthermore, updated applications and technologies of L. plantarum in food and biopharmaceutical industries are also discussed. Understanding the characteristics and functions of L. plantarum will guide the development of related probiotic products and explore the modulatory benefit of L. plantarum supplementations on the prevention and treatment of multiple chronic metabolic diseases.

Keywords

Lactiplantibacillus plantarumDiabetes Obesity Non-alcoholic fatty liver disease Kidney stone disease Cardiovascular diseases

References

[1]

A.G. Abdelhamid, S.S. El-Masry, N.K. El-Dougdoug, Probiotic Lactobacillus and Bifidobacterium strains possess safety characteristics, antiviral activities and host adherence factors revealed by genome mining, EPMA J. 10(4) (2019) 337-350. https://doi.org/10.1007/s13167-019-00184-z.

Strain applied	Source	Dose (CFU/mL)	Intake duration	Host	Results	Reference
Diabetes
L. plantarum HAC01	Korean kimchi	4 × 10⁹	8 weeks	Human	The 2-h postprandial blood glucose level and glycosylated haemoglobin (HbA1c) ↓	Oh et al. [26]
L. plantarum HAC01	Korean kimchi	4 × 10⁹	10 weeks	Mice	1.PEPCK and G6Pase ↓2.Blood glucose and HbA1c levels ↓3.HOMA-IR, islet insulin-positive β cell area ↑4.Phosphorylation of AMPK and Akt ↑5.Akkermansiaceae family and SCFAs in serum ↑	Lee et al. [25]
L. plantarum Probio-093	Korean kimchi	10⁸	8 weeks	Mice	1.Activity of α-glucosidase and α-amylase ↓2.Body weight and blood glucose levels ↓3.Actinobacteria, Bifidobacterium, and Prevotella ↑	Gulnaz et al. [16]
L. plantarum -pMG36e -GLP-1	Engineered strain	10⁹	7 weeks	Monkeys	1.Fasting blood glucose (FPG) ↓2.The intestinal pathogen Prevotella ↑3.Butyrate-producing Alistipes genera ↓4.The 19 metabolism-related pathways ↑	Luo et al. [22]
L. plantarum SS18-5	L. plantarum SS18-5 (CGMCC 14917) mutated inspace from L. plantarum GS18.	10⁹	6 weeks	Rats	1.The weight, FPG, HbA1c, and insulin ↓2.The numbers of E. coli and C. perfringens in gut microbiota ↓3.The numbers of Lactobacillus. sp in gut microbiota ↑	Yang et al. [14]
L. plantarum SCS2	Chinese sausage	10⁹	9 weeks	Mice	1.Blood glucose, body weight and HbA1c levels ↓2.INS levels ↑3.The levels of MDA and ROS ↓4.Levels of antioxidant enzymes ↑	Wu et al. [17]
L. plantarum SHY130	Traditional fermented yak yoghurt (Sichuan, China)	10¹⁰	10 weeks	Mice	1.Regulated blood glucose and significantly improved insulin resistance.2.Inhibited the reduction in β-cell mass and α-cell proliferation in the pancreas.3.GPR43 and GPR41expression in the colon ↑4.The abundance of SCFA-producing bacteria, such as Faecalibaculum, Odoribacter, Alistipes ↑5.The levels of SCFAs ↑	Wang et al. [24]
L. plantarum CC5310 and L. plantarum LRCC5314	Korean kimchi	10¹⁰	12 weeks	Mice	1.Glut4 and adiponectin ↑2.Serum levels of pro-inflammatory cytokines (TNF-α, IL-6) and mRNAs of pro-inflammatory genes (TNF-α, IL-6, Ccl2, leptin) ↓3.Serum corticosterone levels and stress-related genes (Npy, Y2r) ↓	Youn et al. [18]
Obesity
L. plantarum KC28	Kimchi produced in the Pohang region (South Korea)	5 × 10⁹	12 weeks	Mice	1.Weight ↓2.PGC1-α and CPT1-α ↑3.ACOX-1, PPAR-γ, and FAS ↓	Huang et al. [30]
L. plantarum CUL66 (NCIMB 30280)	Healthy human	5 × 10⁸	12 weeks	Mice	1.HDL and TC levels ↑2.LDL/VLDL levels ↓3.Plaque burden and content of lipids and macrophages ↓4.Altered the liver expression of 19 key disease-associated genes.	O\' Morain et al. [117]
L. plantarum CUL66 (NCIMB 30280)	Healthy human	5 × 10¹⁰	6 months	Human	Body weight, BMI, WC and WtHR ↓	Michael et al. [118]
L. plantarum FRT10	Poland sour dough	10¹⁰	8 weeks	Mice	1.Body weight gain, fat weight, and liver triacylglycerols (TGs) and alanine aminotransferase (ALT) concentrations ↓2.Butyricicoccus, Butyricimonas, Intestinimonas, Odoribacter, Alistipes, Lactobacillus, Bifidobacterium, and Akkermansia ↑3.Desulfovibrionaceae, Roseburia, and Lachnoclostridium ↓4.PPARα and CPT1α ↑	Cai et al. [29]
L. plantarum Q180	The feces of adults	4 × 10⁹	12 weeks	Human	1.LDL-cholesterol and apolipoprotein (Apo)B-100 levels ↓2.Total indole and phenol level ↓	Park et al. [60]
L. plantarum LMT1-48	Korean kimchi	10⁹	8 weeks	Mice	1.PPARγ, C/EBPα, FAS, and FABP4 ↓2.Liver weight and liver TGs ↓	Choi et al. [32]
L. plantarum KFY04	Yogurt prepared in Korla, Xinjiang, China	10⁹	8 weeks	Mice	1.Weight, liver, epididymal adipose, and perirenal adipose tissue indices ↓2.Aspartate aminotransferase (AST), ALT, TG, TC and LDL-C ↓3.HDL-C levels ↑4.Mitigated obesity-associated oxidative damage and inflammatory responses.5.PPAR-α, CYP7A1, CPT1 ↑6.PPAR-γ and C/EBPα ↓	Long et al. [119]
L. plantarum CQPC03	Sichuan Paocai, a kind of pickled vegetables, in Chongqing, China	10⁹/kg body weight	8 weeks	Mice	1.Hepatic triglycerides, TC and LDL-C ↓2.HDL-C ↑3.AST, ALT and alkaline phosphatase level ↑4.IL-4 and IL-10 ↑5.IL-6, IL-1β, TNF-α and INF-γ ↓6.Liver SOD and GSH-Px activity ↑7.Liver MDA ↓	Gan et al. [120]
L. plantarum CQPC01	Sichuan Paocai in Chongqing, China,	10⁹/kg body weight	6 weeks	Mice	1.Body weight, the organ indexes ↓2.Lipid levels of serum and liver, and the contents of pro-inflammatory factors ↓3.IL-4 and IL-10 contents ↑4.The C/EBP-α and PPARγ ↓5.CYP7A1, CPT1, LPL, CAT, SOD1, and SOD2 ↑	Gan et al. [31]
L. plantarum LB818	Fermented vegetables (Kimchi)	10⁹	8 weeks	Mice	1.Body weight and total body fat ↓2.ALT, TC, TG ↓3.Bacteroidetes, Akkermansia, Bifidobacterium, and the Bacteroidetes/Firmicutes ratio ↑	Hussain et al. [37]
L. plantarum LC27	Korean kimchi	10⁹	8 weeks	Mice	1.Levels of AST, ALT, TG, TC and lipopolysaccharide in blood and liver ↓2.Activation of NF-κB ↓3.Activation of AMPK ↑4.Expression of claudin-1 and ocludin in the liver and colon ↑5.Firmicutes and Proteobacteria populations ↓	In et al. [38]
L. plantarum HAC01	Korean kimchi	10⁸	8 weeks	Mice	1.Fat accumulation ↓2.Influenced specific bacterial families such as the Lachnospiraceae and Ruminococcaceae.	Park et al. [36]
Kidney stone
L. plantarum WCFS1, recombinant WCFS1OxdC, NC8OxdC	Engineered strain	5 × 10¹⁰	4 weeks	Rats	1.Urinary oxalate, calcium, uric acid, creatinine and serum uric acid, BUN/creatinine ratio ↓2.CaOx crystal deposition↓	Sasikumar et al. [50]
L. plantarum WCFS1Δ Alr	Engineered strain	10¹⁰	2 weeks	Rats	1.Intestinal oxalate degradation↑2.CaOx crystals↓3.Urea and creatinine↓4.OPN and KIM-I expression↓	Paul et al. [49]
L.plantarum N-1	Traditional cheese	10⁸	4 weeks	Rats	1.Urinary oxalic acid, renal osteopontin and CD44 expression↓2.Intestinal inflammation (IL-1β,IL-6,IL-8), TLR4/NF-κB, serum LPS↓3.Tight junction Claudin-2 in the colon↑4.Production of SCFAs↑5.Regulating gut microbiota	Wei et al. [52]
L.plantarum N-1	Traditional cheese	10⁸	4 weeks	Rats	1.Improve the imbalance of intestinal flora2.The level of arginase↓3.Regulating arginine metabolism	Liu et al. [51]
L.plantarum J-15	Human faeces	10⁹	4 weeks	Rats	1.Improve the imbalance of intestinal flora and metabolic disorders2.Renal crystallization, Urinary oxalic acid ↓3.PGD2,PGE2↓4.Intestinal inflammation (IL-1β,IL-6,IL-8,TNF-α), TLR4/NF-κB/COX-2, serum LPS↓5.Tight junction Occludin in the colon↑	Tian et al. [53]
Non-alcoholic fatty liver disease
L. plantarum HAC01	Korean kimchi	4 × 10⁹/day	8 weeks	Human	1.The 2-h postprandial blood glucose↓2.Glycosylated hemoglobin (HbA1c)↓	Oh et al. [26]
L. plantarum MA2	Fermented vegetables	1 × 10⁸/g body weight /day	8 weeks	Rats	1.TC, TG↓2.Claudin-1↑3.LPS-TLR4↓4.TLR4-MYD88, NF-κB, JNK↓	Wang et al. [62]
L. plantarum LC27	Kefir	1 × 10⁹/day	4 weeks	Mice	1.Serum&liver: AST, ALT, TC, TG, LPS↓2.Feces: LPS↓3.NF-κB↓4.Cladin-1, occludin↑5.Firmicutes and Proteobacteria populations in gut microbiota↓	Hye et al. [38]
L. plantarum NA136	Chinese traditional pickle	10⁹/day	16 weeks	Mice	1.Fat tissues, lipids, AST, ALT↓2.SREBP-1/FAS↓3.AMPK, Nrf2↑4.Alleviating insulin resistance	Zhao et al. [64]
L. plantarum FZU3013	Hongqu rice wine	5 × 10⁸/day	8 weeks	Mice	1.Weight gain, serum TC, TG, LDL-C↓2.Liver: TG, TC, BAS,NEFA↓3.Feces: BAS↑4.CYP7A1, BSEP↑5.CD36, SREBP-1C↓	Chen et al. [61]
L. plantarum ATG-K2 and ATG-K6	Korean fermented cabbage	5 × 10⁸/day	8 weeks	Rats	1.Body weight gain, Serum ALT, AST, and ALP↓2.Liver: TC, TG, MDA↓3.SREBP-1C, FAS, C/EBP, ACC↓	Park et al. [60]
L. plantarum WW-FSE	Fermented soybean paste	1 × 10¹⁰/day	12 weeks	Rats	1.Body weight↓2.PPAR, CYP7A1, FADS2↑	Cheng et al. [121]
Hyperlipemia
L. plantarum HNU082	Chinese fermented food (Yucha)	1 × 10⁸/day	4 weeks	Rats	LDL-C↓; TG, TC, HDL-C↑	Shao et al. [66]
L. plantarum LRCC 5273	Kimchi	10⁸/day	6 weeks	Mice	1.TC, LDL↓2.Hepatic mRNA expression of LXR-α and CYP7A1↑3.Intestinal LXR-α and ABCG5↑	Wan et al. [69]
L. plantarum DR9	Fresh milk	10¹⁰/day	12weeks	Rats	1.Serum total cholesterol level↓2.ALP test↓3.Expression of IL-6, AMPKα1↑4.Expression of IL-4, IL-10↓5.Lipid accumulation↓	Lew et al. [71]
L. plantarum DR7	Fresh milk	10¹⁰/day	12weeks	Rats	1.Serum total cholesterol level↓2.Triglyceride level↓3.ALP test↓4.Expression of IL-6↑5.Expression of ABCG5↑6.Expression of SR-B1, ABCA1, Apo A1↑7.Expression of LDL-R, AMPKα1, AMPKα2↑8.Expression of IL-4↓9.Lipid accumulation↓	Lew et al. [71]
L. plantarum ZY08	Baby feces	10⁹/day	8 weeks	Golden Hamsters	1.HDL-C↓2.The number of lipid droplets presenting in the cytoplasm near the nucleus of the hepatocytes↓3.The relative abundance of Faecalibaculum, Ruminococcus, and Desulfovibrio↑	Yang et al. [68]
L. plantarum N-1	Traditional cheese	5 × 10⁹, 4 ml/day	30 days	Rats	1.High DPPH scavenging rates2.Strongest adhesion ability3.Less weight4.TC, TG, LDL-C↓5.HDL↑6.Expression level of the HMG-CoA gene↓7.Production of butyrate and valerate↑	Tian et al. [67]
L. plantarum E680	Chinese traditional fermented pickles	2 × 10⁹, 0.5 mL/day	14 days	Mice	1.Weight2.TC, LDL-C, HDL-C↓	Zheng et al. [73]
L. plantarum ZJUIDS06	Baby feces	10⁹ /100 g body weight /day	8 weeks	Golden Hamsters	1.TC, TG, LDL-C↓2.Levels of total SCFAs↑3.The relative abundance of Parabacteroides, Flavonifractor↑	Yang et al. [68]
L. plantarum VJC38	The GI tract of broiler chicken	3 × 10⁸/day	45 days	Rats	1.TG, TC,LDL-C,GPT, GOT↓2.Fecal cholesterol and cholic acid↑	Nallala et al. [122]
Hypertension
L. plantarum ECGC 13110402	Dairy product	4 × 10⁹/day	12 weeks	Human	1.SBP ↓2.LDL-C ↓3.TAG ↓4.Increase in HDL-C	Costabile, et al. [78]
L. plantarum IS-10506	Traditional Indonesian fermented buffalo milk (Dadih)	10¹⁰/day	14 days	Rabbits	Amlodipine absorption ↑	Saputri et al. [86]
L. plantarum ECGC 13110402	Dairy product	4 × 10⁹/day	9 weeks	Human	1.DBP ↓2.No changes were observed in liver function biomarkers and vitamin D	Keleszade et al. [79]
L. plantarum Lp-LDL	Tomato	4 × 10⁹/day	3 months	Human	1.TC and LDL-C ↓2.SBP and DBP ↓	Derosa et al. [81]
L. plantarum QS670	Cheese	N/A	4 weeks	Rats	Blood pressure ↓	Xia et al. [123]
L. plantarum ATCC 14917	Pickled cabbage	10⁶–10⁷	8 weeks	Rats	1.DBP and SBP ↓2.Plasma ACE activity ↓3.Plasma NO levels ↑	Tong et al. [80]
L. plantarum OLL2712	Human feces	5 × 10⁹ cells/112 g of yogurt	12 weeks	Human	1.Body weight and blood pressure ↑2.HbA1c levels ↓3.Aggravation of chronic inflammation and insulin resistance ↓	Toshimitsu et al. [87]
L. plantarum L-137	Fermented food	N/A	4 weeks	Rats	1.Proportion of regulatory T cells among CD4⁺ T cells in the spleen ↑2.Short-term administration of HK L-137 had no effect on body weight gain or hypertension	Uchinaka et al. [88]
Atherosclerosis
L. plantarum LRCC 5273	Kimchi	1 × 10⁸/day	6 weeks	Mice	1.Serum LDL-cholesterol level and total cholesterol level ↓2.Fecal cholesterol and bile acids excretion ↑	Heo et al. [69]
L. plantarum CUL66	Fermented Foods	5 × 10⁸ /day	12 weeks	Mice	1.Plasma HDL and triglyceride levels ↑2.LDL/VLDL levels ↓3.Frequency of macrophages and T-cells in the bone marrow ↓4.Plaque burden and content of lipids and macrophages ↓	O’ Morain et al. [117]
L. plantarum DMDL 9010	Fermented foods	10⁷/g body weight/day	70 days	Rats	1.Liver cholesterol and triglyceride levels ↓2.Fecal cholesterol and bile acid excretion ↑	Liu et al. [76]
L. plantarum H6	Fermented foods	3 × 10⁸/day	8 weeks	Mice	1.Serum cholesterol levels in C57BL/6 mice ↓2.Intestinal microbial community structure ↑3.Bacteria containing bile salt hydrolase activity ↑	Qu et al. [94]
L. plantarum ZDY04	Fermented foods	1 × 10⁹/day	4 weeks	Mice	1.Serum TMAO and cecal TMA levels ↓2.TMAO-induced atherosclerosis in ApoE^−/− 1.3 % choline-fed mice ↓	Qiu et al. [99]
L. plantarum LS/07	Rectal human swabs	1 × 10⁹/day	25 weeks	Rats	1.β-Galactosidase and β-glucosidase activity ↑2.β-Glucuronidase activity ↓	Hijová et al. [97]
L. plantarum 299v	Human intestinal mucosa	2 × 10⁸/day	6 weeks	Human	1.Bacterial flow-mediated dilation (FMD) ↑2.Endothelium-dependent vasodilation ↑3.Systemic inflammation in men with stable coronary artery disease ↓	Malik et al. [96]
L. plantarum 299v	Human intestinal mucosa	2 × 10⁸/day	6 weeks	Human	1.FMD ↑2.IL-8, IL-12, and leptin ↓3.Induce anti-inflammatory transcriptome changes in human PBMCs that could benefit CAD patients	Hofeld et al. [95]
L. plantarum ATCC 14917	Fresh tea leaves	0.2 mL, 2 × 10⁹/day	12 weeks	Mice	1.Atherosclerotic lesion formation ↓2.LDL, MDA, TNF-α and IL-1β levels ↓	Hassan et al. [98]

Strain applied	Form	Application	Function	Reference
L. plantarum 29V	Liquid	Honey additive	Total cholesterol and triglycerides levels ↓	Landry et al. [124]
L. plantarum A7		Soymilk fortification with probiotic	Beneficial to diabetic patients	Miraghajani et al. [125]
L. Plantarum ATCC 8014		Quinoa flour fermentation	Manufacturing of gluten free baked products	Chis et al. [101]
L. Plantarum SPC-SNU 72-2		Sourdough fermentation	Bread flavor and texture ↑	Park et al. [102]
L. plantarum P8		Expanding fields of healthcare and alternative medicine	Irritable bowel syndrome ↓	Xu et al. [126]
L. plantarum P8		Expanding fields of healthcare and alternative medicine	Alleviating stress and anxiety while enhancing memory and cognition in stressed adults	Lew et al. [127]
L. plantarum TENSIA		Adjunct starter of cheese	Cardiovascular disease risk ↓	Hütt et al. [104]
L. plantarum TWK10		Fermented soymilk	Neuroprotective	Liu et al. [77]
L. plantarum TWK10		Fermented soymilk	Antihypertensive	Liu et al. [105]
L. plantarum ATG-K2 and ATG-K6	Powder	Probiotic supplement	Beneficial in non-alcoholic fatty liver disease	Park et al. [60]
L. plantarum DMDL9010			Cardiovascular risk ↓	Liu et al. [76]
L. plantarum Dad-13			Body weight ↓	Rahayu et al. [110]
L. plantarum 581	Tablet	Probiotic supplement	Constipation ↑	Sun et al. [128]
Bifidobacterium Lactobacillus Triplex Tablets			Intestinal microecology and intestinal barrier function ↑	Jiang et al. [129]
Bifidobacterium Lactobacillus Triplex Tablets			TMAO and TC levels ↓	Jiang et al. [111]
L. plantarum 299v	Capsule	Probiotic supplement	Improving iron status	Axling et al. [130]
L. plantarum LIP-1			Composition of intestinal flora ↑Lipids in hyperlipidemia rats ↓	Song et al. [69]
L. plantarum Vstar 08220		Yogurt additive	Yogurt quality ↑	Ma et al. [112]