We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

The role of probiotics in tissue engineering and regenerative medicine

    Ali Golchin‡

    Cellular & Molecular Research Center, Cellular & Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, 57157993313, Iran

    Department of Clinical Biochemistry & Applied Cell Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, 57157993313, Iran

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Parviz Ranjbarvan‡

    Cellular & Molecular Research Center, Cellular & Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, 57157993313, Iran

    Department of Clinical Biochemistry & Applied Cell Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, 57157993313, Iran

    ‡Authors contributed equally

    Search for more papers by this author

    ,
    Shima Parviz

    Department of Tissue Engineering & Applied cell sciences, School of Advanced Technologies in Medicine, Shiraz University of Medical Sciences, Shiraz, 71348-14336, Iran

    ,
    Amene Shokati

    Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417755469, Iran

    ,
    Roya Naderi

    Neurophysiology Research center & Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, 57157993313, Iran

    ,
    Yousef Rasmi

    Cellular & Molecular Research Center & Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, 57157993313, Iran

    ,
    Samaneh Kiani

    Department of Tissue Engineering & Regenerative Medicine, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, 48157-33971, Iran

    ,
    Faezeh Moradi

    Department of Tissue engineering, Medical Sciences Faculty, Tarbiat Modares University, Tehran, 14117-13116, Iran

    ,
    Fahimeh Heidari

    Department of Molecular Medicine, School of Advanced Medical Sciences & Technologies, Shiraz University of Medical Sciences, Shiraz, 71348-14336, Iran

    Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, 71348-14336, Iran

    ,
    Zohreh Saltanatpour

    Pediatric Cell & Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, 1417755469, Iran

    Stem Cell & Regenerative Medicine Center of Excellence, Tehran University of Medical Sciences, Tehran, 1417755469, Iran

    &
    Akram Alizadeh

    *Author for correspondence:

    E-mail Address: alizadeh.a@semums.ac.ir

    Nervous System Stem Cells Research Center & Department of Tissue Engineering & Applied Cell Sciences, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, 35147-99422, Iran

    Published Online:https://doi.org/10.2217/rme-2022-0209

    Tissue engineering and regenerative medicine (TERM) as an emerging field is a multidisciplinary science and combines basic sciences such as biomaterials science, biology, genetics and medical sciences to achieve functional TERM-based products to regenerate or replace damaged or diseased tissues or organs. Probiotics are useful microorganisms which have multiple effective functions on human health. They have some immunomodulatory and biocompatibility effects and improve wound healing. In this article, we describe the latest findings on probiotics and their pro-healing properties on various body systems that are useable in regenerative medicine. Therefore, this review presents a new perspective on the therapeutic potential of probiotics for TERM.

    Plain language summary

    Tissue engineering and regenerative medicine can design processes or products to restore, repair, or replace injured or diseased cells, tissues or organs. It contains the generation and making use of therapeutic stem cells, and engineered scaffolds for the manufacture of artificial organs. This field focuses on the development and application of new treatments to heal tissues and organs as well as repair functions lost due to damage, defects, disease or aging. The World Health Organization has described probiotics as “live microorganisms that, when administered in sufficient amounts, confer a health advantage on the host”. Probiotics are found naturally in certain foods, such as kimchi and fermented yogurt. They are also found in your gut, where they partake in a type of important bodily processes, such as vitamin production, digestion, mood regulation, and immune function. Probiotics with their suitable pro-healing effects on different systems of the body can be used in regenerative medicine. Probiotic bacteria induce their beneficial effects via proven mechanisms including pathogens killing, modulating the gut microbiota, immunomodulatory effects, and anti-diabetic, anti-obesity and anti-cancer functions. Moreover, recent studies indicated that probiotics could neutralize infections caused by COVID-19. Probiotics are healthy microorganisms that exert multiple positive effects on human health, especially through the battle against pathogens and repairing different types of body tissues.

    References

    • 1. Golchin A, Rekabgardan M, Taheri RA, Nourani MR. Promotion of cell-based therapy: special focus on the cooperation of mesenchymal stem cell therapy and gene therapy for clinical trial studies. In: Advances in Experimental Medicine and Biology (Volume 1119). Springer New York LLC, 103–118 (2018).
    • 2. Golchin A, Shams F, Basiri A et al. Combination therapy of stem cell-derived exosomes and biomaterials in the wound healing. Stem Cell Rev. Reports 2021. 18(6), 1–20 (2022).
    • 3. Salgado AJ, Oliveira JM, Martins A et al. Tissue engineering and regenerative medicine: past, present, and future. Int. Rev. Neurobiol. 108, 1–33 (2013).
    • 4. Sinha A, Sagar S, Madhumathy M, Osborne WJ. Probiotic bacteria in wound healing; an in-vivo study. Iran. J. Biotechnol. 17(4), 11–15 (2019).
    • 5. L J, C V, S I et al. Probiotics or pro-healers: the role of beneficial bacteria in tissue repair. Wound Repair Regen. 25(6), 912–922 (2017).
    • 6. Al-Yassir F, Khoder G, Sugathan S, Saseedharan P, Al Menhali A, Karam SM. Modulation of stem cell progeny by probiotics during regeneration of gastric mucosal erosions. Biology (Basel). 10(7), 596 (2021).
    • 7. Radu N, Roman V, Tănăsescu C. Biomaterials obtained from probiotic consortia of microorganisms. Potential applications in regenerative medicine. Mol. Cryst. Liq. Cryst. 628(1), 115–123 (2016).
    • 8. Kechagia M, Basoulis D, Konstantopoulou S et al. Health benefits of probiotics: a review. ISRN Nutr. 2013, 1–7 (2013).
    • 9. Abatenh E, Gizaw B, Tsegay Z, Tefera G, Aynalem E. Health benefits of probiotics. 0(0), 17–27 (2018).
    • 10. Markowiak P, Ślizewska K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients. 9(9), 1021 (2017).
    • 11. Martin Manuel P, Elena B, Carolina MG, Gabriela P. Oral probiotics supplementation can stimulate the immune system in a stress process. J. Nutr. Intermed. Metab. 8, 29–40 (2017).
    • 12. Ashraf R, Vasiljevic T, Day SL, Smith SC, Donkor ON. Lactic acid bacteria and probiotic organisms induce different cytokine profile and regulatory T cells mechanisms. J. Funct. Foods. 6(1), 395–409 (2014).
    • 13. Aavani F, Biazar E, Heshmatipour Z, Arabameri N, Kamalvand M, Nazbar A. Applications of bacteria and their derived biomaterials for repair and tissue regeneration. Regen. Med. 16(6), 581–605 (2021).
    • 14. Golchin A, Hosseinzadeh S, Jouybar A et al. Wound healing improvement by curcumin-loaded electrospun nanofibers and BFP-MSCs as a bioactive dressing. Polym. Adv. Technol. 31(7), 1519–1531 (2020).
    • 15. Golchin A, Shams F, Kangari P, Azari A, Hosseinzadeh S. Regenerative medicine: injectable cell-based therapeutics and approved products. Adv. Exp. Med. Biol. 1237, 75–95 (2020).
    • 16. Yang L, Han Z, Chen C et al. Novel probiotic-bound oxidized Bletilla striata polysaccharide-chitosan composite hydrogel. Mater. Sci. Eng. C. 117, 111265 (2020).
    • 17. Joy J, Pereira J, Aid-Launais R et al. Gelatin – oxidized carboxymethyl cellulose blend based tubular electrospun scaffold for vascular tissue engineering. Int. J. Biol. Macromol. 107, 1922–1935 (2018).
    • 18. Vågesjö E, Öhnstedt E, Mortier A et al. Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria. Proc. Natl Acad. Sci. 115(8), 1895–1900 (2018).
    • 19. Lukic J, Chen V, Strahinic I et al. Probiotics or pro-healers the role of beneficial bacteria in tissue repair.
    • 20. Rodrigues KL, Gaudino Caputo LR, Tavares Carvalho JC, Evangelista J, Schneedorf JM. Antimicrobial and healing activity of kefir and kefiran extract. Int. J. Antimicrob. Agents. 25(5), 404–408 (2005).
    • 21. Huseini HF, Rahimzadeh G, Fazeli MR, Mehrazma M, Salehi M. Evaluation of wound healing activities of kefir products. Burns 38(5), 719–723 (2012).
    • 22. Roudsari MR, Karimi R, Sohrabvandi S, Mortazavian AM. Health effects of probiotics on the skin. Crit. Rev. Food Sci. Nutr. 55(9), 1219–1240 (2015).
    • 23. Bindurani S. Review: probiotics in dermatology. J. Ski. Sex. Transm. Dis. 1(2), 66–71 (2019).
    • 24. Tagliari E, Campos LF, Campos AC, Costa-Casagrande TA, de Noronha L. Effect of probiotic oral administration on skin wound healing in rats. Arq. Bras. Cir. Dig. 32(3), (2019).
    • 25. Khan MAA, Hussain Z, Ali S, Qamar Z, Imran M, Hafeez FY. Fabrication of electrospun probiotic functionalized nanocomposite scaffolds for infection control and dermal burn healing in a mice model. 5(11), 6109–6116 (2019).
    • 26. Shavandi A, Saeedi P, Gérard P, Jalalvandi E, Cannella D, Bekhit AE-D. The role of microbiota in tissue repair and regeneration. J. Tissue Eng. Regen. Med. 14(3), 539–555 (2020).
    • 27. Manuel J, Molina P. The effect of probioitc treatment on life history allocation, skin regeneration and immunity of ambystoma mexicanum. Southeastern Louisiana University (2019).
    • 28. Liu K, Catchmark JM. Bacterial cellulose/hyaluronic acid nanocomposites production through co-culturing gluconacetobacter hansenii and lactococcus lactis in a two-vessel circulating system. Bioresour. Technol. 290, 121715 (2019).
    • 29. Nicoletti G, Corbella M, Jaber O, Marone P, Scevola D, Faga A. Non-pathogenic microflora of a spring water with regenerative properties. Biomed. Reports. 3(6), 758–762 (2015).
    • 30. Al-Ghazzewi FH, Tester RF. Impact of prebiotics and probiotics on skin health. Benef. Microbes. 5(2), 99–107 (2014).
    • 31. Deng L, Zhang H. Recent advances in probiotics encapsulation by electrospinning. ES Food Agrofor. 2, 3–12 (2020).
    • 32. Ashoori Y, Mohkam M, Heidari R et al. Development and in vivo characterization of probiotic lysate-treated chitosan nanogel as a novel biocompatible formulation for wound healing. Biomed Res. Int. 2020, (2020).
    • 33. Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLOS Biol. 14(8), e1002533 (2016).
    • 34. Bäckhed F, Ding H, Wang T et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. 101(44), 15718–15723 (2004).
    • 35. LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, Ventura M. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr. Opin. Biotechnol. 24(2), 160–168 (2013).
    • 36. Endt K, Stecher B, Chaffron S et al. The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal salmonella diarrhea. PLOS Pathog. 6(9), e1001097 (2010).
    • 37. S M, W J, A A, TA O, EF S, F K. Induction of human beta-defensin 2 by the probiotic Escherichia coli Nissle 1917 is mediated through flagellin. Infect. Immun. 75(5), 2399–2407 (2007).
    • 38. Liu G, Ren W, Fang J et al. l-Glutamine and l-arginine protect against enterotoxigenic Escherichia coli infection via intestinal innate immunity in mice. Amino Acids. 49(12), 1945–1954 (2017).
    • 39. Zyrek AA, Cichon C, Helms S, Enders C, Sonnenborn U, Schmidt MA. Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCζ redistribution resulting in tight junction and epithelial barrier repair. Cell. Microbiol. 9(3), 804–816 (2007).
    • 40. Bermúdez-Humarán LG, Motta JP, Aubry C et al. Serine protease inhibitors protect better than IL-10 and TGF-β anti-inflammatory cytokines against mouse colitis when delivered by recombinant lactococci. Microb. Cell Fact. 14(1), (2015).
    • 41. Steidler L, Hans W, Schotte L et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science (80-.). 289(5483), 1352–1355 (2000).
    • 42. Kumar M, Yadav AK, Verma V et al. Bioengineered probiotics as a new hope for health and diseases: an overview of potential and prospects. Future Microbiol. 11(4), 585–600 (2016).
    • 43. Vandenbroucke K, De Haard H, Beirnaert E et al. Orally administered L. lactis secreting an anti-TNF Nanobody demonstrate efficacy in chronic colitis. Mucosal Immunol. 3(1), 49–56 (2010).
    • 44. Karthik L, Kumar G, Keswani T, Bhattacharyya A, Sarath Chandar S, Bhaskara Rao KV. Protease inhibitors from marine actinobacteria as a potential source for antimalarial compound. PLOS ONE. 9(3), e90972 (2014).
    • 45. Péan N, Doignon I, Garcin I et al. The receptor TGR5 protects the liver from bile acid overload during liver regeneration in mice. Hepatology 58(4), 1451–1460 (2013).
    • 46. Cuenca S, Sanchez E, Santiago A et al. Microbiome composition by pyrosequencing in mesenteric lymph nodes of rats with CCl4-induced cirrhosis. J. Innate Immun. 6(3), 263–271 (2014).
    • 47. Rayes N, Pilarski T, Stockmann M, Bengmark S, Neuhaus P, Seehofer D. Effect of pre- and probiotics on liver regeneration after resection: a randomised, double-blind pilot study. Benef. Microbes. 3(3), 237–244 (2012).
    • 48. Nardone G, Compare D, Liguori E et al. Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury. Am. J. Physiol. - Gastrointest. Liver Physiol. 299(3), G669–G676 (2010).
    • 49. Wang Y, Kirpich I, Liu Y et al. Lactobacillus rhamnosus GG treatment potentiates intestinal hypoxia-inducible factor, promotes intestinal integrity and ameliorates alcohol-induced liver injury. Am. J. Pathol. 179(6), 2866–2875 (2011).
    • 50. Wang Y, Liu Y, Kirpich I et al. Lactobacillus rhamnosus GG reduces hepatic TNFα production and inflammation in chronic alcohol-induced liver injury. J. Nutr. Biochem. 24(9), 1609–1615 (2013).
    • 51. Håkansson Å, Bränning C, Molin G et al. Blueberry husks and probiotics attenuate colorectal inflammation and oncogenesis, and liver injuries in rats exposed to cycling DSS-treatment. PLOS ONE. 7(3), e33510 (2012).
    • 52. Xie Y, Chen H, Zhu B et al. Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation. Microb. Ecol. 68(4), 871–880 (2014).
    • 53. Kirpich IA, Solovieva NV, Leikhter SN et al. Probiotics restore bowel flora and improve liver enzymes in human alcohol-induced liver injury: a pilot study. Alcohol 42(8), 675–682 (2008).
    • 54. Schepper JD, Irwin R, Kang J et al. Probiotics in gut-bone signaling. Underst. gut-bone Signal. axis 225–247 (2017).
    • 55. Hernandez CJ, Guss JD, Luna M, Goldring SR. Links between the microbiome and bone. J. Bone Miner. Res. 31(9), 1638–1646 (2016).
    • 56. Parvaneh K, Jamaluddin R, Karimi G, Erfani R. Effect of probiotics supplementation on bone mineral content and bone mass density. Sci. World J. 2014, (2014).
    • 57. Yan FF, Murugesan GR, Cheng HW. Effects of probiotic supplementation on performance traits, bone mineralization, cecal microbial composition, cytokines and corticosterone in laying hens. Animal. 13(1), 33–41 (2019).
    • 58. Collins FL, Irwin R, Bierhalter H et al. Lactobacillus reuteri 6475 increases bone density in intact females only under an inflammatory setting. PLOS ONE. 11(4), e0153180 (2016).
    • 59. Rodrigues FC, Castro ASB, Rodrigues VC et al. Yacon flour and Bifidobacterium longum modulate bone health in rats. J. Med. Food. 15(7), 664–670 (2012).
    • 60. Tomofuji T, Ekuni D, Azuma T et al. Supplementation of broccoli or Bifidobacterium longum–fermented broccoli suppresses serum lipid peroxidation and osteoclast differentiation on alveolar bone surface in rats fed a high-cholesterol diet. Nutr. Res. 32(4), 301–307 (2012).
    • 61. Mutuş R, Kocabağli N, Alp M, Acar N, Eren M, Gezen ŞŞ. The effect of dietary probiotic supplementation on tibial bone characteristics and strength in broilers. Poult. Sci. 85(9), 1621–1625 (2006).
    • 62. Chiang S-S, Pan T-M. Beneficial effects of Lactobacillus paracasei subsp. paracasei NTU 101 and its fermented products. Appl. Microbiol. Biotechnol. 93(3), 903–916 (2012).
    • 63. Kim JG, Lee E, Kim SH, Whang KY, Oh S, Imm J-Y. Effects of a Lactobacillus casei 393 fermented milk product on bone metabolism in ovariectomised rats. Int. Dairy J. 19(11), 690–695 (2009).
    • 64. Narva M, Collin M, Lamberg-Allardt C et al. Effects of long-term intervention with Lactobacillus helveticus-fermented milk on bone mineral density and bone mineral content in growing rats. Ann. Nutr. Metab. 48(4), 228–234 (2004).
    • 65. Kirjavainen PV, Salminen SJ, Isolauri E. Probiotic bacteria in the management of atopic disease: underscoring the importance of viability. J. Pediatr. Gastroenterol. Nutr. 36(2), 223–227 (2003).
    • 66. Levi YL de AS, Picchi RN, Silva EKT et al. Probiotic administration increases mandibular bone mineral density on rats exposed to cigarette smoke inhalation. Braz. Dent. J. 30(6), 634–640 (2019).
    • 67. Parvaneh K, Ebrahimi M, Sabran MR et al. Probiotics (Bifidobacterium longum) increase bone mass density and upregulate Sparc and Bmp-2 genes in rats with bone loss resulting from ovariectomy. Biomed Res. Int. 2015, (2015).
    • 68. Wu S, Lei L, Bao C et al. An injectable and antibacterial calcium phosphate scaffold inhibiting Staphylococcus aureus and supporting stem cells for bone regeneration. Mater. Sci. Eng. C. 120, 111688 (2021).
    • 69. Tan L, Fu J, Feng F et al. Engineered probiotics biofilm enhances osseointegration via immunoregulation and anti-infection. Sci. Adv. 6(46), eaba5723 (2020).
    • 70. Karska-Wysocki B, Bazo M, Smoragiewicz W. Antibacterial activity of Lactobacillus acidophilus and Lactobacillus casei against methicillin-resistant Staphylococcus aureus (MRSA). Microbiol. Res. 165(8), 674–686 (2010).
    • 71. Ghanbari M, Jami M, Kneifel W, Domig KJ. Antimicrobial activity and partial characterization of bacteriocins produced by lactobacilli isolated from Sturgeon fish. Food Control. 32(2), 379–385 (2013).
    • 72. González A, Sabio L, Hurtado C et al. Entrapping living probiotics into collagen scaffolds: a new class of biomaterials for antibiotic-free therapy of bacterial vaginosis. Adv. Mater. Technol. 5(7), 2000137 (2020).
    • 73. Mullick P, Das G, Aiyagari R. Probiotic bacteria cell surface-associated protein mineralized hydroxyapatite incorporated in porous scaffold: in vitro evaluation for bone cell growth and differentiation. Mater. Sci. Eng. C. 126, 112101 (2021).
    • 74. Fan J, Yang X, Li J et al. Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway. Oncotarget. 8(11), 17475–17490 (2017).
    • 75. Bindels LB, Delzenne NM. Muscle wasting: the gut microbiota as a new therapeutic target? Int. J. Biochem. Cell Biol. 45(10), 2186–2190 (2013).
    • 76. Wu CS, Wei Q, Wang H et al. Protective effects of ghrelin on fasting-induced muscle atrophy in aging mice. Journals Gerontol. - Ser. A Biol. Sci. Med. Sci. 75(4), 621–630 (2020).
    • 77. Cheng LH, Cheng SH, Wu CC et al. Lactobacillus paracasei PS23 dietary supplementation alleviates muscle aging via ghrelin stimulation in D-galactose-induced aging mice. J. Funct. Foods. 85, 104651 (2021).
    • 78. Harnett JE, Pyne DB, McKune AJ, Penm J, Pumpa KL. Probiotic supplementation elicits favourable changes in muscle soreness and sleep quality in rugby players. J. Sci. Med. Sport. 24(2), 195–199 (2021).
    • 79. Jäger R, Shields KA, Lowery RP et al. Probiotic Bacillus coagulans GBI-30, 6086 reduces exercise-induced muscle damage and increases recovery. PeerJ. 2016(7), e2276 (2016).
    • 80. Townsend JR, Bender D, Vantrease WC et al. Effects of probiotic (Bacillus subtilis de111) supplementation on immune function, hormonal status, and physical performance in division i baseball players. Sports. 6(3), 70 (2018).
    • 81. Cruz-Jentoft AJ, Dawson Hughes B, Scott D, Sanders KM, Rizzoli R. Nutritional strategies for maintaining muscle mass and strength from middle age to later life: a narrative review. Maturitas. 132, 57–64 (2020).
    • 82. Jäger R, Zaragoza J, Purpura M et al. Probiotic administration increases amino acid absorption from plant protein: a placebo-controlled, randomized, double-blind, multicenter, crossover study. Probiotics Antimicrob. Proteins. 12(4), 1330–1339 (2020).
    • 83. Pan W, Kang Y. Gut microbiota and chronic kidney disease: implications for novel mechanistic insights and therapeutic strategies. Int. Urol. Nephrol. 50(2), 289–299 (2018).
    • 84. Di Cerbo A, Palmieri B, Aponte M, Morales-Medina JC, Iannitti T. Mechanisms and therapeutic effectiveness of lactobacilli. J. Clin. Pathol. 69(3), 187–203 (2016).
    • 85. Anders HJ, Andersen K, Stecher B. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int. 83(6), 1010–1016 (2013).
    • 86. Rukavina Mikusic NL, Kouyoumdzian NM, Choi MR. Gut microbiota and chronic kidney disease: evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis. Pflugers Arch. Eur. J. Physiol. 472(3), 303–320 (2020).
    • 87. Ramezani A, Raj DS. The gut microbiome, kidney disease, and targeted interventions. J. Am. Soc. Nephrol. 25(4), 657–670 (2014).
    • 88. Wong J, Piceno YM, DeSantis TZ, Pahl M, Andersen GL, Vaziri ND. Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD. Am. J. Nephrol. 39(3), 230–237 (2014).
    • 89. Gryp T, Huys GRB, Joossens M, Biesen W Van, Glorieux G, Vaneechoutte M. Isolation and quantification of uremic toxin precursor-generating gut bacteria in chronic kidney disease patients. Int. J. Mol. Sci. 21(6), 1986 (2020).
    • 90. Vaziri ND, Wong J, Pahl M et al. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 83(2), 308–315 (2013).
    • 91. Watanabe H, Miyamoto Y, Honda D et al. P-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. Kidney Int. 83(4), 582–592 (2013).
    • 92. Sun CY, Chang SC, Wu MS. Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLOS ONE. 7(3), e34026 (2012).
    • 93. Ranganathan N, Ranganathan P, Friedman EA et al. Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Adv. Ther. 27(9), 634–647 (2010).
    • 94. Borges NA, Carmo FL, Stockler-Pinto MB et al. Probiotic supplementation in chronic kidney disease: a double-blind, randomized, placebo-controlled trial. J. Ren. Nutr. 28(1), 28–36 (2018).
    • 95. Koppe L, Mafra D, Fouque D. Probiotics and chronic kidney disease. Kidney Int. 88(5), 958–966 (2015).
    • 96. Jia L, Jia Q, Yang J, Jia R, Zhang H. Efficacy of probiotics supplementation on chronic kidney disease: a systematic review and meta-analysis. Kidney Blood Press. Res. 43(5), 1623–1635 (2018).
    • 97. Thongprayoon C, Kaewput W, Hatch ST et al. Effects of probiotics on inflammation and uremic toxins among patients on dialysis: a systematic review and meta-analysis. Dig. Dis. Sci. 64(2), 469–479 (2019).
    • 98. Di Iorio BR, Rocchetti MT, De Angelis M et al. Nutritional therapy modulates intestinal microbiota and reduces serum levels of total and free indoxyl sulfate and p-cresyl sulfate in chronic kidney disease (Medika study). J. Clin. Med. 8(9), 1424 (2019).
    • 99. Rocchetti MT, Di Iorio BR, Vacca M et al. Ketoanalogs' effects on intestinal microbiota modulation and uremic toxins serum levels in chronic kidney disease (Medika2 study). J. Clin. Med. 10(4), 1–18 (2021).
    • 100. Dehghani H, Heidari F, Mozaffari-Khosravi H, Nouri-Majelan N, Dehghani A. Synbiotic supplementations for Azotemia in patients with chronic kidney disease: a randomized controlled trial. Iran. J. Kidney Dis. 10(6), 351–357 (2016).
    • 101. Sabetkish N, Sabetkish S, Mohseni MJ, Kajbafzadeh AM. Prevention of renal scarring in acute pyelonephritis by probiotic therapy: an experimental study. Probiotics Antimicrob. Proteins. 11(1), 158–164 (2019).
    • 102. Prasetyo RV, Surono I, Soemyarso NA et al. Lactobacillus plantarum IS-10506 promotes renal tubular regeneration in pyelonephritic rats. Benef. Microbes. 11(1), 59–66 (2020).
    • 103. Wynn SG. Probiotics in veterinary practice. J. Am. Vet. Med. Assoc. 234(5), 606–613 (2009).
    • 104. Den Besten G, Van Eunen K, Groen AK, Venema K, Reijngoud D-J, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 54(9), 2325–2340 (2013).
    • 105. Cosola C, De Angelis M, Rocchetti MT et al. Beta-glucans supplementation associates with reduction in P-cresyl sulfate levels and improved endothelial vascular reactivity in healthy individuals. PLOS ONE. 12(1), e0169635 (2017).
    • 106. Li L, Ma L, Fu P. Gut microbiota-derived short-chain fatty acids and kidney diseases. Drug Des. Devel. Ther. 11, 3531–3542 (2017).
    • 107. Pluznick JL. Gut microbiota in renal physiology: focus on short-chain fatty acids and their receptors. Kidney Int. 90(6), 1191–1198 (2016).
    • 108. Siciliano RA, Mazzeo MF. Molecular mechanisms of probiotic action: a proteomic perspective. Curr. Opin. Microbiol. 15(3), 390–396 (2012).
    • 109. Wang IK, Wu YY, Yang YF et al. The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised, double-blind, placebo-controlled trial. Benef. Microbes. 6(4), 423–430 (2015).
    • 110. Shariaty Z, Shan GRM, Farajollahi M, Amerian M, Pour NB. The effects of probiotic supplement on hemoglobin in chronic renal failure patients under hemodialysis: a randomized clinical trial. J. Res. Med. Sci. 22(3), (2017).
    • 111. Peng J, Xiao X, Hu M, Zhang X. Interaction between gut microbiome and cardiovascular disease. Life Sci. 214, 153–157 (2018).
    • 112. Thushara RM, Gangadaran S, Solati Z, Moghadasian MH. Cardiovascular benefits of probiotics: a review of experimental and clinical studies. Food Funct. 7(2), 632–642 (2016).
    • 113. Lye HS, Kuan CY, Ewe JA, Fung WY, Liong MT. The improvement of hypertension by probiotics: effects on cholesterol, diabetes, renin, and phytoestrogens. Int. J. Mol. Sci. 10(9), 3755–3775 (2009).
    • 114. Ng SC, Hart AL, Kamm MA, Stagg AJ, Knight SC. Mechanisms of action of probiotics: recent advances. Inflamm. Bowel Dis. 15(2), 300–310 (2009).
    • 115. Wu ZX, Li SF, Chen H et al. The changes of gut microbiota after acute myocardial infarction in rats. PLOS ONE. 12(7), e0180717 (2017).
    • 116. Higashikawa F, Noda M, Awaya T et al. Antiobesity effect of Pediococcus pentosaceus LP28 on overweight subjects: a randomized, double-blind, placebo-controlled clinical trial. Eur. J. Clin. Nutr. 70(5), 582–587 (2016).
    • 117. Inoue K, Shirai T, Ochiai H et al. Blood-pressure-lowering effect of a novel fermented milk containing γ-aminobutyric acid (GABA) in mild hypertensives. Eur. J. Clin. Nutr. 57(3), 490–495 (2003).
    • 118. Lam V, Su J, Hsu A, Gross GJ, Salzman NH, Baker JE. Intestinal microbial metabolites are linked to severity of myocardial infarction in rats. PLOS ONE. 11(8), e0160840 (2016).
    • 119. Moludi J, Saiedi S, Ebrahimi B, Alizadeh M, Khajebishak Y, Ghadimi SS. Probiotics supplementation on cardiac remodeling following myocardial infarction: a single-center double-blind clinical study. J. Cardiovasc. Transl. Res. 14(2), 299–307 (2021).
    • 120. Chan YK, El-Nezami H, Chen Y, Kinnunen K, Kirjavainen PV. Probiotic mixture VSL# 3 reduce high fat diet induced vascular inflammation and atherosclerosis in ApoE−/− mice. Amb Express. 6(1), 1–8 (2016).
    • 121. Gan XT, Ettinger G, Huang CX et al. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat. Circ. Hear. Fail. 7(3), 491–499 (2014).
    • 122. Azuma M, Takahashi K, Fukuda T et al. Taurine attenuates hypertrophy induced by angiotensin II in cultured neonatal rat cardiac myocytes. Eur. J. Pharmacol. 403(3), 181–188 (2000).
    • 123. Costanza AC, Moscavitch SD, Faria Neto HCC, Mesquita ET. Probiotic therapy with Saccharomyces boulardii for heart failure patients: a randomized, double-blind, placebo-controlled pilot trial. Int. J. Cardiol. 179, 348–350 (2015).
    • 124. Eckburg PB, Bik EM, Bernstein CN et al. Microbiology: diversity of the human intestinal microbial flora. Science (80-.). 308(5728), 1635–1638 (2005).
    • 125. Tang WHW, Wang Z, Kennedy DJ et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ. Res. 116(3), 448–455 (2014).
    • 126. Stubbs JR, House JA, Ocque AJ et al. Serum Trimethylamine-N-Oxide is Elevated in CKD and correlates with coronary atherosclerosis burden. J. Am. Soc. Nephrol. 27(1), 305–313 (2016).
    • 127. Scheppach W. Effects of short chain fatty acids on gut morphology and function. Gut 35(Suppl. 1), S35–S38 (1994).
    • 128. Ufnal M, Jazwiec R, Dadlez M, Drapala A, Sikora M, Skrzypecki J. Trimethylamine-N-Oxide: a carnitine-derived metabolite that prolongs the hypertensive effect of angiotensin II in rats. Can. J. Cardiol. 30(12), 1700–1705 (2014).
    • 129. Tang TWH, Chen HC, Chen CY et al. Loss of gut microbiota alters immune system composition and cripples postinfarction cardiac repair. Circulation 139(5), 647–659 (2019).
    • 130. Zilla P, Von Oppell U, Deutsch M. The endothelium: a key to the future. J. Card. Surg. 8(1), 32–60 (1993).
    • 131. Meinhart JG, Deutsch M, Fischlein T, Howanietz N, Fröschl A, Zilla P. Clinical autologous in vitro endothelialization of 153 infrainguinal ePTFE grafts. Ann. Thorac. Surg. 71(5), S327–S331 (2001).
    • 132. Crovesy L, Ostrowski M, Ferreira DMTP, Rosado EL, Soares-Mota M. Effect of Lactobacillus on body weight and body fat in overweight subjects: a systematic review of randomized controlled clinical trials. Int. J. Obes. 41(11), 1607–1614 (2017).
    • 133. Koppinger MP, Lopez-Pier MA, Skaria R, Harris PR, Konhilas JP. Lactobacillus reuteri attenuates cardiac injury without lowering cholesterol in low-density lipoprotein receptor-deficient mice fed standard chow. Am. J. Physiol. - Hear. Circ. Physiol. 319(1), H32–H41 (2020).
    • 134. Lam VY, Su J, Koprowski S et al. Intestinal microbiota determine severity of myocardial infarction in rats. FASEB J. 26(4), 1727–1735 (2012).
    • 135. Sefidgari-Abrasi S, Karimi P, Roshangar L et al. Lactobacillus plantarum and Inulin: therapeutic agents to enhance cardiac ob receptor expression and suppress cardiac apoptosis in type 2 diabetic rats. J. Diabetes Res. 2020, (2020).
    • 136. De Smet I, Van Hoorde L, De Saeyer N, Vande Woestyne M, Verstraete W. In vitro study of bile salt hydrolase (BSH) activity of BSH isogenic lactobacillus plantarum 80 strains and estimation of cholesterol lowering through enhanced BSH activity. Microb. Ecol. Health Dis. 7(6), 315–329 (1994).
    • 137. Begley M, Hill C, Gahan CGM. Bile salt hydrolase activity in probiotics. Appl. Environ. Microbiol. 72(3), 1729–1738 (2006).
    • 138. Klein A, Friedrich U, Vogelsang H, Jahreis G. Lactobacillus acidophilus 74-2 and Bifidobacterium animalis subsp lactis DGCC 420 modulate unspecific cellular immune response in healthy adults. Eur. J. Clin. Nutr. 62(5), 584–593 (2008).
    • 139. Mohan JC, Arora R, Khalilullah M. Preliminary observations on effect of Lactobacillus sporogenes on serum lipid levels in hypercholesterolemic patients. Indian J. Med. Res. - Sect. B Biomed. Res. Other Than Infect. Dis. 92(DEC.), 431–432 (1990).
    • 140. Lin SY, Ayres JW, Winkler W, Sandine WE. Lactobacillus effects on cholesterol: in vitro and in vivo results. J. Dairy Sci. 72(11), 2885–2899 (1989).
    • 141. Abd El-Gawad IA, El-Sayed EM, Hafez SA, El-Zeini HM, Saleh FA. The hypocholesterolaemic effect of milk yoghurt and soy-yoghurt containing bifidobacteria in rats fed on a cholesterol-enriched diet. Int. Dairy J. 15(1), 37–44 (2005).
    • 142. Kumar M, Nagpal R, Kumar R et al. Cholesterol-lowering probiotics as potential biotherapeutics for metabolic diseases. Exp. Diabetes Res. 2012, (2012).
    • 143. Xiao JZ, Kondo S, Takahashi N et al. Effects of milk products fermented by Bifidobacterium longum on blood lipids in rats and healthy adult male volunteers. J. Dairy Sci. 86(7), 2452–2461 (2003).
    • 144. Du Toit M, Franz CMAP, Dicks LMT et al. Characterisation and selection of probiotic lactobacilli for a preliminary minipig feeding trial and their effect on serum cholesterol levels, faeces pH and faeces moisture content. Int. J. Food Microbiol. 40(1–2), 93–104 (1998).
    • 145. Liu YW, Liong MT, Tsai YC. New perspectives of Lactobacillus plantarum as a probiotic: the gut-heart-brain axis. J. Microbiol. 56(9), 601–613 (2018).
    • 146. Ting WJ, Kuo WW, Hsieh DJY et al. Heat killed lactobacillus reuteri GMNL-263 reduces fibrosis effects on the liver and heart in high fat diet-hamsters via TGF-β suppression. Int. J. Mol. Sci. 16(10), 25881–25896 (2015).
    • 147. Ettinger G, Burton JP, Gloor GB, Reid G. Lactobacillus rhamnosus GR-1 attenuates induction of hypertrophy in cardiomyocytes but not through secreted protein MSP-1 (p75). PLOS ONE. 12(1), e0168622 (2017).
    • 148. Xu H, Wang J, Cai J et al. Protective effect of lactobacillus rhamnosus gg and its supernatant against myocardial dysfunction in obese mice exposed to intermittent hypoxia is associated with the activation of nrf2 pathway. Int. J. Biol. Sci. 15(11), 2471–2483 (2019).
    • 149. Suganya K, Koo BS. Gut–brain axis: role of gut microbiota on neurological disorders and how probiotics/prebiotics beneficially modulate microbial and immune pathways to improve brain functions. Int. J. Mol. Sci. 21(20), 1–29 (2020).
    • 150. Sudo N, Chida Y, Aiba Y et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. 558(1), 263–275 (2004).
    • 151. Mayer EA. Gut feelings: the emerging biology of gut–brain communication. Nat. Rev. Neurosci. 12(8), 453–466 (2011).
    • 152. Wang H, Lee IS, Braun C, Enck P. Effect of probiotics on central nervous system functions in animals and humans: a systematic review. J. Neurogastroenterol. Motil. 22(4), 589–605 (2016).
    • 153. Bravo JA, Forsythe P, Chew MV et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl Acad. Sci. U. S. A. 108(38), 16050–16055 (2011).
    • 154. O'Sullivan E, Barrett E, Grenham S et al. BDNF expression in the hippocampus of maternally separated rats: Does Bifidobacterium breve 6330 alter BDNF levels? Benef. Microbes. 2(3), 199–207 (2011).
    • 155. Ait-Belgnaoui A, Durand H, Cartier C et al. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology 37(11), 1885–1895 (2012).
    • 156. Zhu S, Jiang Y, Xu K et al. The progress of gut microbiome research related to brain disorders. J. Neuroinflammation. 17(1), 1–20 (2020).
    • 157. Braniste V, Al-Asmakh M, Kowal C et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci. Transl. Med. 6(263), 263ra158–263ra158 (2014).
    • 158. Saulnier DM, Ringel Y, Heyman MB et al. The intestinal microbiome, probiotics and prebiotics in neurogastroenterology. Gut Microbes. 4(1), 17–27 (2013).
    • 159. Azm SAN, Djazayeri A, Safa M et al. Lactobacilli and bifidobacteria ameliorate memory and learning deficits and oxidative stress in β-amyloid (1–42) injected rats. Appl. Physiol. Nutr. Metab. 43(7), 718–726 (2018).
    • 160. Liang S, Wang T, Hu X et al. Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress. Neuroscience 310, 561–577 (2015).
    • 161. Wang T, Hu X, Liang S et al. Lactobacillus fermentum NS9 restores the antibiotic induced physiological and psychological abnormalities in rats. Benef. Microbes. 6(5), 707–717 (2015).
    • 162. Akbari E, Asemi Z, Daneshvar Kakhaki R et al. Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer's disease: a randomized, double-blind and controlled trial. Front. Aging Neurosci. 8, 256 (2016).
    • 163. Abraham D, Feher J, Scuderi GL et al. Exercise and probiotics attenuate the development of Alzheimer's disease in transgenic mice: role of microbiome. Exp. Gerontol. 115, 122–131 (2019).
    • 164. Fang X. Microbial treatment: the potential application for Parkinson's disease. Neurol. Sci. 40(1), 51–58 (2019).
    • 165. Bonfili L, Cecarini V, Berardi S et al. Microbiota modulation counteracts Alzheimer's disease progression influencing neuronal proteolysis and gut hormones plasma levels. Sci. Rep. 7(1), 1–21 (2017).
    • 166. Cassani E, Privitera G, Pezzoli G et al. Use of probiotics for the treatment of constipation in Parkinson's disease patients. Minerva Gastroenterol. Dietol. 57(2), 117–121 (2011).
    • 167. Barichella M, Pacchetti C, Bolliri C et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease. Neurology 87(12), 1274–1280 (2016).
    • 168. Georgescu D, Ancusa OE, Georgescu LA, Ionita I, Reisz D. Nonmotor gastrointestinal disorders in older patients with Parkinson's disease: is there hope? Clin. Interv. Aging. 11, 1601–1608 (2016).
    • 169. Pierantozzi M, Pietroiusti A, Sancesario G et al. Reduced L-dopa absorption and increased clinical fluctuations in Helicobacter pylori-infected Parkinson's disease patients. Neurol. Sci. 22(1), 89–91 (2001).
    • 170. Liu WH, Chuang HL, Huang YT et al. Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice. Behav. Brain Res. 298, 202–209 (2016).
    • 171. Pinto-Sanchez MI, Hall GB, Ghajar K et al. Probiotic Bifidobacterium longum NCC3001 reduces depression scores and alters brain activity: a pilot study in patients with irritable bowel syndrome. Gastroenterology 153(2), 448–459.e8 (2017).
    • 172. Khalighi AR, Khalighi MR, Behdani R et al. Evaluating the efficacy of probiotic on treatment in patients with small intestinal bacterial overgrowth (SIBO) - A pilot study. Indian J. Med. Res. 140(5), 604–608 (2014).
    • 173. Gazerani P. Probiotics for Parkinson's disease. Int. J. Mol. Sci. 20(17), 4121 (2019).
    • 174. Lavasani S, Dzhambazov B, Nouri M et al. A novel probiotic mixture exerts a therapeutic effect on experimental autoimmune encephalomyelitis mediated by IL-10 producing regulatory T cells. PLOS ONE. 5(2), e9009 (2010).
    • 175. Kwon HK, Kim GC, Kim Y et al. Amelioration of experimental autoimmune encephalomyelitis by probiotic mixture is mediated by a shift in T helper cell immune response. Clin. Immunol. 146(3), 217–227 (2013).
    • 176. Umbrello G, Esposito S. Microbiota and neurologic diseases: potential effects of probiotics. J. Transl. Med. 14(1), 1–11 (2016).
    • 177. Brandi J, Cheri S, Manfredi M et al. Exploring the wound healing, anti-inflammatory, anti-pathogenic and proteomic effects of lactic acid bacteria on keratinocytes. Sci. Rep. 10(1), 1–14 (2020).
    • 178. Lew LC, Gan CY, Liong MT. Dermal bioactives from lactobacilli and bifidobacteria. Ann. Microbiol. 63(3), 1047–1055 (2013).
    • 179. Corbett GA, Crosby DA, McAuliffe FM. Probiotic therapy in couples with infertility: a systematic review. Eur. J. Obstet. Gynecol. Reprod. Biol. 256, 95–100 (2021).
    • 180. Proctor LM, Chhibba S, Mcewen J et al. The NIH human microbiome project. Hum. Microbiota How Microb. Communities Affect Heal. Dis. 19(12), 1–50 (2013).
    • 181. Ravel J, Gajer P, Abdo Z et al. Vaginal microbiome of reproductive-age women. Proc. Natl Acad. Sci. USA 108(Suppl. 1), 4680–4687 (2011).
    • 182. Ohri M, Prabha V. Isolation of a sperm-agglutinating factor from Staphylococcus aureus isolated from a woman with unexplained infertility. Fertil. Steril. 84(5), 1539–1541 (2005).
    • 183. Bhandari P, Rishi P, Prabha V. Positive effect of probiotic Lactobacillus plantarum in reversing LPS-induced infertility in a mouse model. J. Med. Microbiol. 65(5), 345–350 (2016).
    • 184. Anukam KC, Osazuwa E, Osemene GI, Ehigiagbe F, Bruce AW, Reid G. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect. 8(12–13), 2772–2776 (2006).
    • 185. Younis N, Mahasneh A. Probiotics and the envisaged role in treating human infertility. Middle East Fertil. Soc. J. 25(1), 1–9 (2020).
    • 186. Barbonetti A, Cinque B, Vassallo MRC et al. Effect of vaginal probiotic lactobacilli on in vitro-induced sperm lipid peroxidation and its impact on sperm motility and viability. Fertil. Steril. 95(8), 2485–2488 (2011).
    • 187. Pascual LM, Daniele MB, Giordano W, Pájaro MC, Barberis IL. Purification and partial characterization of novel bacteriocin L23 produced by Lactobacillus fermentum L23. Curr. Microbiol. 56(4), 397–402 (2008).
    • 188. Bhandari P, Prabha V. Evaluation of profertility effect of probiotic Lactobacillus plantarum 2621 in a murine model. Indian J. Med. Res. 142(JULY), 79–84 (2015).
    • 189. Ibrahim HAM, Zhu Y, Wu C et al. Erratum: selenium-enriched probiotics improves murine male fertility compromised by high fat diet (Biological Trace Element Research DOI: 10.1007/s12011-011-9308-2). Biol. Trace Elem. Res. 147(1–3), 428 (2012).
    • 190. Chen XL, Gong LZ, Xu JX. Antioxidative activity and protective effect of probiotics against high-fat diet-induced sperm damage in rats. Animal. 7(2), 287–292 (2013).
    • 191. Helli B, Kavianpour M, Ghaedi E, Dadfar M, Haghighian HK. Probiotic effects on sperm parameters, oxidative stress index, inflammatory factors and sex hormones in infertile men. Hum. Fertil. 1–9 (2020).
    • 192. Poutahidis T, Springer A, Levkovich T et al. Probiotic microbes sustain youthful serum testosterone levels and testicular size in aging mice. PLOS ONE. 9(1), e84877 (2014).
    • 193. Kaufmann U, Domig KJ, Lippitsch CI et al. Ability of an orally administered lactobacilli preparation to improve the quality of the neovaginal microflora in male to female transsexual women. Eur. J. Obstet. Gynecol. Reprod. Biol. 172(1), 102–105 (2014).
    • 194. Birse KD, Kratzer K, Zuend CF et al. The neovaginal microbiome of transgender women post-gender reassignment surgery. Microbiome. 8(1), 1–13 (2020).
    • 195. McNerney MP, Doiron KE, Ng TL, Chang TZ, Silver PA. Theranostic cells: emerging clinical applications of synthetic biology. Nat. Rev. Genet. 22(11), 730–746 (2021).
    • 196. Khan S, Hauptman R, Kelly L. Engineering the microbiome to prevent adverse events: challenges and opportunities. Annu. Rev. Pharmacol. Toxicol. 61, 159–179 (2021).
    • 197. Gomaa EZ. Human gut microbiota/microbiome in health and diseases: a review. Antonie van Leeuwenhoek, Int. J. Gen. Mol. Microbiol. 113(12), 2019–2040 (2020).
    • 198. Peirce JM, Alviña K. The role of inflammation and the gut microbiome in depression and anxiety. J. Neurosci. Res. 97(10), 1223–1241 (2019).
    • 199. Qiu W, Zhou Y, Li Z et al. Application of antibiotics/antimicrobial agents on dental caries. Biomed Res. Int. 2020, (2020).
    • 200. Harper A, Vijayakumar V, Ouwehand AC et al. Viral infections, the microbiome, and probiotics. Front. Cell. Infect. Microbiol. 925 (2021).
    • 201. Lorente-picón M, Laguna A. New avenues for parkinson's disease therapeutics: disease-modifying strategies based on the gut microbiota. Biomolecules. 11(3), 1–39 (2021).
    • 202. Spacova I, Dodiya HB, Happel AU et al. Future of probiotics and prebiotics and the implications for early career researchers. Front. Microbiol. 11, 1400 (2020).
    • 203. Alemzadeh E, Oryan A. Application of encapsulated probiotics in health care. J. Exp. Pathol. 1(1), (2020).
    • 204. Zhu Y, Wang Z, Bai L, Deng J, Zhou Q. Biomaterial-based encapsulated probiotics for biomedical applications: current status and future perspectives. Mater. Des. 210, 110018 (2021).
    • 205. Mettu S, Hathi Z, Athukoralalage S et al. Perspective on constructing cellulose-hydrogel-based gut-like bioreactors for growth and delivery of multiple-strain probiotic bacteria. J. Agric. Food Chem. 69(17), 4946–4959 (2021).
    • 206. Ngo N, Choucair K, Creeden JF et al. Bifidobacterium spp: the promising trojan horse in the era of precision oncology. Futur. Oncol. 15(33), 3861–3876 (2019).
    • 207. Liao N, Pang B, Jin H et al. Potential of lactic acid bacteria derived polysaccharides for the delivery and controlled release of oral probiotics. J. Control. Release. 323, 110–124 (2020).
    • 208. Li S, Jiang W, Zheng C et al. Oral delivery of bacteria: basic principles and biomedical applications. J. Control. Rel. 327, 801–833 (2020).
    • 209. Thakur AK, Singh I. Formulation strategies for the oral delivery of probiotics: a review. Biointerface Res. Appl. Chem. 9(5), 4327–4333 (2019).
    • 210. Gautier T, Gall SD-L, Sweidan A et al. Next-generation probiotics and their metabolites in covid-19. Microorganisms. 9(5), 941 (2021).
    • 211. Ailioaie LM, Litscher G. Probiotics, photobiomodulation, and disease management: controversies and challenges. Int. J. Mol. Sci. 22(9), 4942 (2021).
    • 212. Andrade JC, Almeida D, Domingos M et al. Commensal obligate anaerobic bacteria and health: production, storage, and delivery strategies. Front. Bioeng. Biotechnol. 8, 1–23 (2020).
    • 213. Cheng WY, Wu CY, Yu J. The role of gut microbiota in cancer treatment: friend or foe? Gut 69(10), 1867–1876 (2020).
    • 214. Sedighi M, Zahedi Bialvaei A, Hamblin MR et al. Therapeutic bacteria to combat cancer; current advances, challenges, and opportunities. Cancer Med. 8(6), 3167–3181 (2019).
    • 215. Liu J, Liu C, Yue J. Radiotherapy and the gut microbiome: facts and fiction. Radiat. Oncol. 16(1), 1–15 (2021).
    • 216. Zhou Z, Chen X, Sheng H et al. Engineering probiotics as living diagnostics and therapeutics for improving human health. Microb. Cell Fact. 19(1), 1–12 (2020).
    • 217. Ke X, Walker A, Haange S-B et al. Synbiotic-driven improvement of metabolic disturbances is associated with changes in the gut microbiome in diet-induced obese mice. Mol. Metab. 22, 96–109 (2019).