NFS Journal

Systematic Review: Preservative and Therapeutic Efficacy of Probiotic Lactic Acid

Bacteria
--Manuscript Draft--

Manuscript Number:

Article Type: Review Article

Keywords: Probiotic lactic acid bacteria

Corresponding Author: Desalegn Amenu

Wollega University
ETHIOPIA

First Author: Desalegn Amenu

Order of Authors: Desalegn Amenu

Ayantu Nugusa

Temesgen Tafesse

Abstract: This systematic review synthesizes recent studies to provide an in-depth

understanding of their dual functions. LAB enhance food safety and extend shelf life by
producing organic acids and bacteriocins and outcompeting spoilage organisms. They
are particularly effective in preserving dairy, fermented vegetables, and meat products.
Additionally, LAB modulate gut microbiota, improve intestinal barrier function, and
boost immune responses. Clinical trials and in vivo studies indicate that LAB can
prevent gastrointestinal infections, reduce serum cholesterol levels, and offer
antioxidant protection. However, the effectiveness of LAB varies based on strain,
dosage, and administration method. Further research is needed to optimize LAB
strains for specific applications in food preservation and health. In summary, LAB offer
natural solutions for food preservation and health improvement, but more studies are
required to fully understand their mechanisms and develop targeted probiotic
formulations.

Suggested Reviewers: Reda Nemo

redanemo@gmail.com

Girmaye Kenasa
girmayekenasa@gmail.com

Opposed Reviewers:

Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation
Cover Letter

Systematic Review: Preservative and Therapeutic Efficacy of Probiotic Lactic

Acid Bacteria
Desalegn Amenu1, Ayantu Nugusa1 and Temesgen Tafesse2
1. Wollega University, College of Natural and Computational sciences, Biology
Department, Nekemte, Ethiopia.
2. Armuear Hansen Research Institute, Microbiology and Microbial-biotechnology, Addis
Ababa, Ethiopia.
Highlights

 Exploration of non-dairy products, functional foods, and genetically modified LAB for

advanced probiotic properties.

 LAB probiotics improve digestive health and boost immunity, alleviating conditions like

IBS and diarrhea.

 LAB extend shelf life by inhibiting spoilage and pathogenic microorganisms through

antimicrobial substances.

 LAB Used as natural alternatives to chemical preservatives in dairy, meat, and fermented

vegetables.

 LAB are Effective in preventing and treating respiratory and urogenital infections by

competing with pathogens and modulating immune responses.

Abstract

Systematic Review: Preservative and Therapeutic Efficacy of Probiotic Lactic

Acid Bacteria
Desalegn Amenu1, Ayantu Nugusa1 and Temesgen Tafesse2
1. Wollega University, College of Natural and Computational sciences, Biology
Department, Nekemte, Ethiopia.
2. Armuear Hansen Research Institute, Microbiology and Microbial-biotechnology, Addis
Ababa, Ethiopia.

Abstract

Title: Systematic Review: Probiotic Lactic Acid Bacteria (LAB) in Food Preservation and
Therapeutic Applications

Introduction: Probiotic lactic acid bacteria (LAB) play pivotal roles in both food preservation and
human health, leveraging their antimicrobial properties and therapeutic benefits. This systematic
review synthesizes recent research to comprehensively assess the preservative efficiency and
therapeutic efficacy of LAB.

Methodology: A thorough search was conducted across PubMed, Google Scholar, and
ScienceDirect databases, covering studies published from 2010 to 2023. Selection criteria included
relevance, methodological rigor, and quality of evidence.

Results and discussion: LAB demonstrate significant efficacy in extending the shelf life and
ensuring the safety of various food products, such as dairy, fermented vegetables, and meat
products. In parallel, LAB exhibit substantial therapeutic potential by modulating gut microbiota,
enhancing intestinal barrier function, and boosting immune responses. Clinical trials and in vivo
studies highlight their effectiveness in preventing gastrointestinal infections, reducing serum
cholesterol levels, and providing antioxidant protection. Despite the promising evidence, the
efficacy of LAB varies significantly depending on the strain, dosage, and mode of administration.
This review underscores the need for further research to optimize LAB strains for specific
preservative and therapeutic applications. Overall, LAB represent a valuable asset in both the
food industry and medical field, offering natural solutions for food preservation and health
improvement. Future studies should focus on elucidating the precise mechanisms of action and
developing targeted probiotic formulations to maximize their benefits.
Challenges and Future Directions: Variability in LAB efficacy based on strain specificity,
dosage, and administration mode. Need for further research to optimize LAB strains for targeted
food preservation and therapeutic applications. Elucidating precise molecular mechanisms
underlying LAB actions in both food and health contexts.

Conclusion: Probiotic LAB represent a dual-purpose solution in the food industry and healthcare,
offering natural alternatives for food preservation and health improvement. Future studies should
focus on refining probiotic formulations, understanding their mechanisms of action, and
optimizing their applications in both food technology and clinical practice. This review
underscores the promising potential of LAB as versatile agents in promoting both food safety and
human well-being.

Key words: Probiotic Lactic Acid Bacteria, Preservative Efficiency, Therapeutic Efficacy, Food
Preservation, and Gut Health.
Manuscript File Click here to view linked References

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5 1 Systematic Review: Preservative and Therapeutic Efficacy of Probiotic Lactic
6 2 Acid Bacteria
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3 Desalegn Amenu1, Ayantu Nugusa1 and Temesgen Tafesse2
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9 4 1. Wollega University, College of Natural and Computational sciences, Biology
10 5 Department, Nekemte, Ethiopia.
11 6 2. Armuear Hansen Research Institute, Microbiology and Microbial-biotechnology, Addis
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13 7 Ababa, Ethiopia.
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15 8 Abstract
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18 9 Title: Systematic Review: Probiotic Lactic Acid Bacteria (LAB) in Food Preservation and
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20 10 Therapeutic Applications
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23 11 Introduction: Probiotic lactic acid bacteria (LAB) play pivotal roles in both food preservation and
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25 12 human health, leveraging their antimicrobial properties and therapeutic benefits. This systematic
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27 13 review synthesizes recent research to comprehensively assess the preservative efficiency and
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29 14 therapeutic efficacy of LAB.
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32 15 Methodology: A thorough search was conducted across PubMed, Google Scholar, and
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34 16 ScienceDirect databases, covering studies published from 2010 to 2023. Selection criteria included
35 17 relevance, methodological rigor, and quality of evidence.
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37
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18 Results and discussion: LAB demonstrate significant efficacy in extending the shelf life and
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40 19 ensuring the safety of various food products, such as dairy, fermented vegetables, and meat
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42 20 products. In parallel, LAB exhibit substantial therapeutic potential by modulating gut microbiota,
43
44 21 enhancing intestinal barrier function, and boosting immune responses. Clinical trials and in vivo
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46 22 studies highlight their effectiveness in preventing gastrointestinal infections, reducing serum
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48 23 cholesterol levels, and providing antioxidant protection. Despite the promising evidence, the
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24 efficacy of LAB varies significantly depending on the strain, dosage, and mode of administration.
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51 25 This review underscores the need for further research to optimize LAB strains for specific
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53 26 preservative and therapeutic applications. Overall, LAB represent a valuable asset in both the
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55 27 food industry and medical field, offering natural solutions for food preservation and health
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57 28 improvement. Future studies should focus on elucidating the precise mechanisms of action and
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59 29 developing targeted probiotic formulations to maximize their benefits.
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4 30 Challenges and Future Directions: Variability in LAB efficacy based on strain specificity,
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6 31 dosage, and administration mode. Need for further research to optimize LAB strains for targeted
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8 32 food preservation and therapeutic applications. Elucidating precise molecular mechanisms
9
10 33 underlying LAB actions in both food and health contexts.
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13 34 Conclusion: Probiotic LAB represent a dual-purpose solution in the food industry and healthcare,
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15 35 offering natural alternatives for food preservation and health improvement. Future studies should
16
17 36 focus on refining probiotic formulations, understanding their mechanisms of action, and
18 37 optimizing their applications in both food technology and clinical practice. This review
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20 38 underscores the promising potential of LAB as versatile agents in promoting both food safety and
21
22 39 human well-being.
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25 40 Key words: Probiotic Lactic Acid Bacteria, Preservative Efficiency, Therapeutic Efficacy, Food
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27 41 Preservation, and Gut Health.
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30 42 1. Introduction
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33 43 Probiotic lactic acid bacteria (LAB) have garnered significant attention due to their dual roles in
34 44 food preservation and therapeutic applications. These microorganisms, commonly found in
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36 45 fermented foods, possess the ability to inhibit the growth of pathogenic bacteria through the
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38 46 production of organic acids, bacteriocins, and other antimicrobial substances(Khushboo et al.,
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40 47 2023; Zapaśnik et al., 2022). Their preservative efficacy not only extends the shelf life of food
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42 48 products but also enhances their safety and nutritional value. In addition to their preservative
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49 properties, LAB exhibit numerous health benefits, including the modulation of gut microbiota,
45 50 enhancement of immune response, and potential therapeutic effects against gastrointestinal
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47 51 disorders, infections, and even certain chronic diseases (Cotter et al., 2005; Umu et al., 2017).
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50 52 The preservative efficacy of LAB is primarily attributed to their metabolic activities, which lead
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52 53 to the production of lactic acid and other organic acids(Zapaśnik et al., 2022). These acids lower
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54 54 the pH of the food environment, creating conditions unfavorable for spoilage and pathogenic
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56 55 microorganisms(Cotter et al., 2005). Furthermore, LAB can produce bacteriocins—proteinaceous
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58 56 substances with bactericidal properties that target specific bacterial strains. For instance, nisin, a
59 57 well-known bacteriocin produced by Lactococcus lactis, is widely used in the food industry for its
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4 58 effectiveness against a broad spectrum of Gram-positive bacteria(Anumudu et al., 2021). These
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6 59 dual mechanisms highlight the pivotal role of LAB in enhancing the shelf life and safety of food
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8 60 products, making them indispensable in food preservation practices. Continued research into the
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10 61 metabolic pathways and applications of LAB promises further innovations in food technology and
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12 62 microbiology, ensuring both quality and safety in the global food supply chain.
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15 63 The therapeutic potential of LAB is equally compelling (Rezvani et al., 2016). They contribute to
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17 64 the maintenance of a healthy gut microbiota, which is essential for proper digestion, nutrient
18 65 absorption, and immune function. Studies have shown that specific strains of LAB can alleviate
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20 66 symptoms of irritable bowel syndrome (IBS), reduce the incidence of antibiotic-associated
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22 67 diarrhea, and improve outcomes in inflammatory bowel disease (IBD) (Distrutti et al., 2016;
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24 68 Skoufou et al., 2024).Moreover, LAB have been investigated for their potential to prevent and
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26 69 manage infections, particularly those involving the gastrointestinal and respiratory tracts(Petrariu
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70 et al., 2023). Emerging evidence also suggests a role for LAB in modulating the immune system
29 71 and reducing the risk of certain chronic diseases, such as cardiovascular disease and diabetes (Zhao
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31 72 et al., 2023). Hence, the diverse therapeutic applications of LAB underscore their significant role
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33 73 in enhancing human health beyond food preservation. Continued research into their mechanisms
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35 74 and clinical efficacy promises to further illuminate their potential in preventive and therapeutic
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37 75 medicine.
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40 76 In summary, the preservation effectiveness of LAB hinges on their ability to produce lactic acid
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42 77 and other organic acids, which create an acidic environment detrimental to spoilage and pathogenic
43 78 microorganisms (Zapaśnik et al., 2022; Cotter et al., 2005). Additionally, LAB contribute to food
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45 79 safety by synthesizing bacteriocins such as nisin, which exhibit targeted antibacterial activity
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47 80 against specific types of bacteria, notably Gram-positive species (Anumudu et al., 2021).
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50 81 Understanding these mechanisms is crucial for several reasons. First, it underpins the scientific
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52 82 basis for using LAB in food preservation, extending shelf life and ensuring product safety without
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54 83 relying on synthetic additives. Second, the ability of LAB to produce natural antimicrobial
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56 84 compounds like bacteriocins offers a sustainable alternative to traditional preservatives, aligning
57 85 with consumer preferences for natural and minimally processed foods. Finally, ongoing research
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59 86 into LAB metabolism and bacteriocin production holds promise for developing novel food
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4 87 preservation strategies that are effective, eco-friendly, and compatible with modern food
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6 88 production practices. In essence, the study of LAB's preservative abilities not only enhances our
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8 89 understanding of microbial ecology in food systems but also contributes to advancing food
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10 90 technology towards safer and more sustainable practices.
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13 91
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16 92
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22 94
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25 95
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28 96
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31 97 2. Methodology
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33 98 Search Strategy and Databases Utilized:
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35 99  Databases:
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37 100 o PubMed, Scopus, Web of Science, Cochrane Library, Embase.
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39 101 o These databases were chosen for their comprehensive coverage of biomedical
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102 literature, systematic reviews
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42 103  Search Terms:
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44 104 o Keywords related to "probiotic lactic acid bacteria", "preservation", "therapeutic
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46 105 efficacy"
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48 106 o Boolean operators (AND, OR) was used to combine these keywords effectively to
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50 107 capture relevant studies.
51 108  Date and Language Restrictions:
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53 109 o Articles published from 2010 to 2024 were included to focus on recent
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55 110 advancements in probiotic LAB research.
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57 111 o Only articles published in the English language was included due to resource
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59 112 constraints.
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4 113 Screening and Selection Process of Articles:
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6 114  Initial Screening:
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8 115 o Titles and abstracts of identified articles were screened independently by two
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10 116 reviewers.
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12 117 o Articles deemed potentially relevant based on inclusion criteria were proceed to
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118 full-text review.
15 119  Full-Text Review:
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17 120 o Full-text articles were retrieved and reviewed to assess eligibility for final inclusion
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19 121 in the systematic review.
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21 122 o Reasons for exclusion of articles were documented, such as irrelevant outcomes or
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23 123 non-human studies.
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4 125 3. Preservative efficiency of probiotics
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126 The preservative efficiency of probiotics, particularly lactic acid bacteria (LAB), is a crucial aspect
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9 127 in food science and industry. Probiotics exert their preservative effects through several key
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11 128 mechanisms:
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14 129 3.1.Acid Production:
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17 130 Probiotic LAB, such as various strains of Lactobacillus and Bifidobacterium, utilize their ability
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19 131 to ferment carbohydrates present in food substrates. Through fermentation, LAB metabolize sugars
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21 132 into lactic acid and other organic acids (Cotter et al., 2005).This metabolic process leads to a
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23 133 decrease in the pH of the food matrix. The lowered pH creates an acidic environment that is
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134 inhospitable to the growth and survival of spoilage microorganisms and pathogens (Zapaśnik et
26 135 al., 2022). The acidity not only directly inhibits microbial growth but also enhances the stability
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28 136 of proteins and other macromolecules in the food, thereby extending its shelf life(Khushboo et al.,
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30 137 2023).
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33 138 3.2.Production of Antimicrobial Peptides:
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36 139 In addition to acid production, probiotic LAB are capable of synthesizing antimicrobial peptides
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38 140 known as bacteriocins. One of the well-known examples is nisin, produced by Lactococcus lactis.
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40 141 Bacteriocins exhibit selective antimicrobial activity against specific bacterial strains, particularly
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42 142 Gram-positive bacteria (Anumudu et al., 2021).These peptides function by disrupting the integrity
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143 of bacterial cell membranes, leading to cell lysis and eventual death of the targeted
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45 144 microorganisms(Cotter et al., 2005). This dual mechanism of acidification and bacteriocin
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47 145 production allows probiotic LAB to effectively control microbial populations in food, contributing
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49 146 significantly to its preservation.
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52 147 3.3.Competitive Exclusion:
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55 148 Furthermore, probiotic LAB can outcompete and inhibit the growth of pathogenic or spoilage
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57 149 microorganisms through competitive exclusion. By colonizing food matrices and adhering to
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59 150 surfaces, LAB create a competitive advantage for themselves, limiting the available nutrients and
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4 151 space for other bacteria to thrive (Cotter et al., 2005). This competitive exclusion mechanism
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6 152 further contributes to the preservation of food products by preventing contamination and spoilage.3
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9 153 3.4.Interaction with Food Matrix:
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12 154 The effectiveness of probiotic lactic acid bacteria (LAB) in food preservation depends significantly
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14 155 on their interaction with the specific characteristics of the food matrix. Recent studies underscore
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16 156 several key factors within the food environment that influence LAB's growth, metabolic activity,
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18 157 and ultimately their preservation capabilities (Zapaśnik et al., 2022). LAB are particularly sensitive
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20 158 to pH levels, thriving in mildly acidic conditions typically ranging from pH 4 to 5. This acidity is
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159 primarily generated through the fermentation process, where LAB produce lactic acid. Optimal
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23 160 pH conditions are crucial as they support the growth and activity of LAB, enhancing their ability
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25 161 to outcompete spoilage microorganisms and pathogens that prefer neutral or alkaline environments
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27 162 (Cotter et al., 2005).
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30 163 Another critical factor is the moisture content of the food matrix. LAB require sufficient moisture
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32 164 to sustain their metabolic processes and enzymatic activities. In environments with low moisture
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34 165 content, such as dried meats or cereals, LAB may enter a dormant state or exhibit reduced
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166 metabolic activity, which limits their effectiveness in preserving the product (Zapaśnik et al.,
37 167 2022). Nutrient availability also plays a pivotal role in shaping LAB's preservation efficacy.
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39 168 Adequate nutrients, including carbohydrates and nitrogen sources, support robust LAB
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41 169 metabolism. This metabolic activity enables LAB to produce antimicrobial compounds like
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43 170 organic acids and bacteriocins, which inhibit the growth of spoilage bacteria. In nutrient-rich
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45 171 environments, LAB can more effectively contribute to food preservation efforts by controlling
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172 microbial populations (Cotter et al., 2005). Additionally, the composition and structure of the food
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48 173 matrix, such as its texture, fat content, and the presence of preservatives, influence LAB activity.
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50 174 For instance, the distribution and survival of LAB within the food product can be influenced by
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52 175 the presence of fats or oils, impacting their ability to uniformly exert preservative effects
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54 176 throughout the matrix (Zapaśnik et al., 2022).
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4 179 3.5.Antimicrobial activity
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180 Antimicrobial activity is a crucial aspect of probiotic lactic acid bacteria's (LAB) role in food
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9 181 preservation. LAB are known to produce antimicrobial compounds, notably bacteriocins, which
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11 182 exhibit targeted bactericidal effects against a wide range of bacteria, particularly Gram-positive
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13 183 strains. These bacteriocins play a significant role in inhibiting the growth of pathogens and
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15 184 spoilage microorganisms, thereby enhancing food safety and extending shelf life (Anumudu et al.,
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17 185 2021).
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20 186 Bacteriocins are proteinaceous peptides synthesized by LAB as a natural defense mechanism
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187 against competing microorganisms in their environment. They function by disrupting the cell
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23 188 membranes of target bacteria, leading to cell lysis and subsequent death of the microbial cells
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25 189 (Cotter et al., 2005). This selective antimicrobial action makes bacteriocins effective natural
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27 190 preservatives in food systems, as they specifically target harmful bacteria while sparing beneficial
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29 191 microflora. Studies have demonstrated the efficacy of bacteriocins, such as nisin produced by
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31 192 Lactococcus lactis, against various foodborne pathogens including Listeria monocytogenes and
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193 Staphylococcus aureus (Anumudu et al., 2021). The application of bacteriocins in food products
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34 194 helps mitigate the risk of bacterial contamination and spoilage, contributing to improved food
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36 195 quality and safety.
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39 196 Experimental Studies:
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42 197 Experimental models and studies in food systems consistently demonstrate the effectiveness of
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44 198 probiotic LAB in extending the shelf life of various products. For instance, research has shown
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46 199 that supplementation with LAB in fermented dairy products significantly reduces the growth of
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48 200 spoilage bacteria. This is achieved through mechanisms such as pH reduction and production of
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201 antimicrobial compounds like bacteriocins, thereby enhancing product stability and safety
51 202 (Zapaśnik et al., 2022).
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54 203
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4 205 Clinical Trials and Field Applications:
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206 Clinical trials and field applications provide further evidence of probiotic LAB's preservation
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9 207 efficacy in real-world settings. These studies evaluate LAB's impact on microbial populations,
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11 208 sensory attributes, and consumer acceptability in food products. For example, clinical trials have
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13 209 validated the ability of LAB to maintain food safety by controlling pathogenic bacteria while
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15 210 preserving sensory qualities that are crucial for consumer satisfaction (Cotter et al., 2005).
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18 211 Overall, the combination of experimental evidence and clinical data supports the practical
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20 212 application of probiotic LAB in enhancing food preservation strategies. These findings not only
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213 underscore LAB's role in extending shelf life and improving food safety but also highlight their
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23 214 potential as natural alternatives to traditional preservatives in meeting consumer preferences for
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25 215 healthier and minimally processed foods. Continued research aims to further optimize LAB-based
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27 216 preservation methods and expand their application across a broader range of food products.
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30 217 4. Therapeutic Efficacy of LAB
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33 218 The therapeutic efficacy of probiotic lactic acid bacteria (LAB) spans a wide range of health
34 219 benefits, supported by evidence from various studies and clinical trials. Here's an outline detailing
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36 220 specific aspects and clinical evidence of their therapeutic applications:
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39 221 4.1.Promotion of Beneficial Bacteria by Lactic Acid Bacteria
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42 222 Lactic Acid Bacteria (LAB), including Lactobacillus and Bifidobacterium species, are
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44 223 instrumental in fostering a healthy gut microbiota through diverse mechanisms supported by recent
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46 224 research. Firstly, LAB are adept at adhering to and colonizing the mucosal surfaces of the
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48 225 gastrointestinal tract, facilitating prolonged interactions with the gut microbiota and enhancing
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50 226 their beneficial effects (Pessione, 2012). Secondly, LAB are prolific producers of metabolites that
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227 create an optimal environment for beneficial bacteria: Short-chain fatty acids (SCFAs) such as
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53 228 acetate, propionate, and butyrate are key metabolites generated through the fermentation of dietary
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55 229 fibers. These SCFAs not only serve as vital energy sources for intestinal epithelial cells but also
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57 230 contribute significantly to maintaining gut barrier integrity and immune function (Fusco et al.,
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59 231 2023; Silva et al., 2020). Antimicrobial peptides (AMPs) produced by LAB exhibit potent
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4 232 antimicrobial properties. These peptides selectively inhibit the growth of pathogenic bacteria while
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6 233 promoting the growth and proliferation of beneficial bacteria like Bifidobacteria, thereby
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8 234 contributing to gut health (Castillo et al., 2012). Furthermore, LAB play a crucial role in
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10 235 modulating the pH levels of the intestinal environment through the production of lactic acid. This
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12 236 acidification creates an inhospitable environment for many pathogenic bacteria while supporting
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237 the growth of acid-tolerant beneficial bacteria(Pessione, 2012)
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17 238 LAB also exert influence over nutrient availability within the gut, enhancing the accessibility of
18 239 essential compounds that support the growth and vitality of beneficial microbes(Daria & Nigam,
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20 240 2022). Lastly, LAB engage in beneficial cross-feeding interactions with other members of the gut
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22 241 microbiota. For instance, they enzymatically degrade complex carbohydrates into simpler sugars
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24 242 and SCFAs. These breakdown products serve as substrates for neighboring beneficial bacteria that
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26 243 may lack the necessary enzymes for initial degradation, fostering a symbiotic relationship within
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244 the gut ecosystem(Flint et al., 2012).
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31 245 4.2.Modulation of Immune Response by Probiotic Lactic Acid Bacteria
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34 246 Probiotic Lactic Acid Bacteria (LAB), including species like Lactobacillus and Bifidobacterium,
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36 247 play a crucial role in modulating immune responses by regulating immune system activity and
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248 mitigating inflammation and allergic responses through various mechanisms. Firstly, LAB
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39 249 enhance barrier function within the gastrointestinal tract by fortifying the intestinal epithelial
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41 250 barrier. This reinforcement helps prevent the translocation of pathogens and antigens from the gut
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43 251 into the bloodstream, thereby reducing the overall burden on the immune system and promoting
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45 252 gut homeostasis(Zhang et al., 2016).
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48 253 Secondly, LAB interact with intestinal epithelial cells and immune cells through toll-like receptors
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50 254 (TLRs). This interaction triggers regulatory pathways that balance immune responses,
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255 distinguishing between harmful pathogens and beneficial commensal microorganisms. By
53 256 modulating immune activation, LAB contribute to maintaining immune homeostasis in the
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55 257 gut(Frosali et al., 2015). LAB also exert anti-inflammatory effects by stimulating the production
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57 258 of anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta
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59 259 (TGF-β) by immune cells. These cytokines help to suppress excessive immune responses and
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4 260 inflammation within the gut mucosa, contributing to overall gut health (Iyer & Cheng, 2012).
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6 261 Furthermore, LAB can inhibit the nuclear factor-kappa B (NF-kB) pathway in immune cells. This
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8 262 pathway is pivotal in regulating the expression of genes involved in inflammation. By dampening
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10 263 NF-kB activation, LAB mitigate inflammation within the gut, thus supporting immune balance
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12 264 and gut health(Bąska & Norbury, 2022).
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15 265 In terms of allergic responses, LAB influence the balance between T helper 17 (Th17) cells and
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17 266 regulatory T cells (Tregs) in the gut. This balance is critical for immune tolerance and the
18 267 prevention of allergic reactions. LAB promote the differentiation of Tregs while suppressing the
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20 268 differentiation of Th17 cells, thereby reducing allergic inflammation(Cheng et al., 2019).
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22 269 Moreover, LAB can modulate the production of immunoglobulin E (IgE), an antibody involved in
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24 270 allergic reactions. By decreasing IgE levels, LAB contribute to mitigating allergic sensitization
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26 271 and responses, further highlighting their role in immune modulation(Shamji et al., 2021). In
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272 conclusion, probiotic Lactic Acid Bacteria exhibit diverse mechanisms through which they
29 273 modulate immune responses, reduce inflammation, and alleviate allergic reactions in the gut.
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31 274 These insights underscore their potential therapeutic applications in immune-related disorders and
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33 275 underscore the importance of further research into their mechanisms and clinical efficacy.
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36 276 4.3.Clinical Applications of Probiotic Lactic Acid Bacteria (LAB)
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38 277 4.3.1. Gastrointestinal Health
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40 278 Probiotic Lactic Acid Bacteria (LAB), including species like Lactobacillus and Bifidobacterium,
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42 279 exhibit a wide range of clinical applications across various health domains, particularly in
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44 280 gastrointestinal health. In the realm of gastrointestinal health, LAB have proven effective in
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281 managing different types of diarrhea, including antibiotic-associated diarrhea and infectious
47 282 diarrhea(Petrariu et al., 2023).They play a crucial role in restoring the balance of gut microbiota
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49 283 that is often disrupted by antibiotic use. Additionally, LAB inhibit the growth of pathogenic
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51 284 bacteria, thereby promoting a healthier gut environment (Kesavelu & Jog, 2023).
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54 285 Moreover, probiotic LAB supplementation has shown promise in the management of symptoms
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56 286 associated with Irritable Bowel Syndrome (IBS). Individuals with IBS often experience discomfort
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58 287 such as bloating, abdominal pain, and irregular bowel movements. LAB contribute to improving
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60 288 gut health by reducing inflammation and enhancing bowel function, which can alleviate these
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4 289 distressing symptoms(Didari et al., 2015; More et al., 2020). In conclusion, the therapeutic benefits
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6 290 of probiotic Lactic Acid Bacteria extend to gastrointestinal health through their ability to restore
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8 291 microbiota balance, inhibit pathogenic bacteria, and alleviate symptoms of conditions like diarrhea
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10 292 and IBS. These findings underscore their potential as valuable interventions in clinical practice,
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12 293 supporting overall gut health and well-being.
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15 294 4.3.2. Immune System Support
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17 295 Probiotic Lactic Acid Bacteria (LAB), such as Lactobacillus and Bifidobacterium species,
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19 296 contribute significantly to immune system support through their beneficial effects on respiratory
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21 297 infections, allergies, and autoimmune diseases. LAB enhance mucosal immunity and support
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23 298 respiratory tract health, which helps in both preventing and reducing the severity of respiratory
24
25
299 infections like the common cold and influenza (Ahanchian & Jafari, 2016; Mettelman et al., 2022).
26 300 By bolstering mucosal barriers and promoting immune responses in the respiratory tract, LAB
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28 301 reduce the likelihood of infection and aid in quicker recovery from respiratory illnesses.
29
30
31 302 In terms of allergy management and modulation of autoimmune diseases, LAB play a pivotal role
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33 303 in regulating immune responses. They promote immune tolerance and mitigate allergic reactions
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35 304 by influencing the differentiation of immune cells and modulating cytokine production crucial for
36
37 305 maintaining immune balance (Goswami et al., 2022; Mukuku et al., 2019). This modulation helps
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39 306 in reducing allergic sensitization and symptoms, as well as potentially alleviating autoimmune
40 307 responses by promoting tolerance towards self-antigens.
41
42
43 308 In summary, probiotic Lactic Acid Bacteria exert profound effects on immune system support,
44
45 309 benefiting respiratory health by enhancing mucosal immunity and reducing the incidence of
46
47 310 infections. Furthermore, their role in allergy management and autoimmune disease modulation
48
49 311 highlights their therapeutic potential in maintaining immune balance and overall health. Continued
50
51 312 research into their mechanisms and clinical applications is crucial for fully realizing their
52
53 313 therapeutic benefits in these areas.
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56 314
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59 315
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2
3
4 316 4.3.3. Metabolic Health
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6
7 317 Probiotic Lactic Acid Bacteria (LAB), including species like Lactobacillus and Bifidobacterium,
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9 318 have emerged as promising agents in promoting metabolic health, particularly in the contexts of
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319 obesity, metabolic syndrome, and related disorders. LAB have been investigated for their potential
11
12 320 impact on obesity and metabolic syndrome by influencing energy metabolism and adipose tissue
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14 321 function. Research suggests that LAB supplementation may contribute to weight management by
15
16 322 modulating energy harvest from the diet and affecting fat accumulation processes within the
17
18 323 body(Lin et al., 2022). Furthermore, probiotic LAB have shown beneficial effects in regulating
19
20 324 lipid metabolism and glucose homeostasis, essential components in preventing and managing
21
325 metabolic disorders such as dyslipidemia and diabetes. Studies indicate that LAB supplementation
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23 326 can help improve lipid profiles by reducing total cholesterol and triglyceride levels, while also
24
25 327 enhancing glucose metabolism and insulin sensitivity(Xiao et al., 2023). In summary, the
26
27 328 therapeutic potential of probiotic Lactic Acid Bacteria extends beyond gastrointestinal health to
28
29 329 include significant impacts on metabolic health. Their ability to influence energy metabolism,
30
31 330 adipose tissue function, lipid profiles, and glucose homeostasis underscores their role as promising
32 331 interventions in managing obesity, metabolic syndrome, and related disorders. Continued research
33
34 332 is essential to elucidate specific mechanisms and optimize their clinical applications in promoting
35
36 333 metabolic well-being.
37
38
39 334 4.3.4. Evidence from clinical studies
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41
42 335 Clinical studies and meta-analyses have consistently demonstrated the efficacy of probiotic Lactic
43 336 Acid Bacteria (LAB), including species like Lactobacillus and Bifidobacterium, across a spectrum
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45 337 of health conditions. In terms of gastrointestinal health, probiotic LAB have shown effectiveness
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47 338 in managing diarrhea(McFarland, 2006) highlighted their ability to reduce the severity and
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49 339 duration of antibiotic-associated and infectious diarrhea by restoring gut microbiota balance.
50
51 340 Similarly, (Wollny et al., 2021) underscored their role in alleviating symptoms of Irritable Bowel
52
53 341 Syndrome (IBS), with certain strains proving beneficial in reducing abdominal pain and improving
54 342 bowel function.
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56
57
343 Regarding immune system support, probiotic LAB have been studied for their preventive effects
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59 344 against respiratory infections. Zhao et al. (2023) found that probiotics, particularly strains like
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4 345 Lactobacillus and Bifidobacterium, significantly lowered the incidence and duration of upper
5
6 346 respiratory tract infections in both children and adults. In terms of allergy management and
7
8 347 autoimmune diseases, Darbandi et al. (2021) highlighted LAB's role in modulating immune
9
10 348 responses, which can reduce allergic symptoms and potentially mitigate autoimmune conditions
11
12 349 such as atopic dermatitis and rheumatoid arthritis.
13
14
15 350 In the realm of metabolic health, probiotic LAB have shown promise in managing obesity and
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17 351 metabolic syndrome(Ruiz Rodríguez et al., 2022) reviewed trials indicating that specific LAB
18 352 strains contribute to modest weight loss and improvements in metabolic parameters such as lipid
19
20 353 profiles and insulin sensitivity. In addition, Yao et al. (2017) further supported these findings by
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22 354 demonstrating that probiotic supplementation improves lipid metabolism and glucose homeostasis
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24 355 in individuals with type 2 diabetes. These studies collectively underscore the diverse therapeutic
25
26 356 potential of probiotic Lactic Acid Bacteria in promoting health across different systems. From
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28
357 gastrointestinal benefits to immune system modulation and metabolic improvements, probiotics
29 358 offer multifaceted benefits supported by clinical evidence. However, variations in study designs,
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31 359 populations, probiotic strains, and dosages suggest the need for tailored approaches in clinical
32
33 360 practice. Continued research is essential to optimize the use of probiotics and further elucidate
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35 361 their mechanisms of action for targeted therapeutic applications.
36
37
38 362 Futures perspective
39
40
41 363 The future of probiotic Lactic Acid Bacteria promises advancements in personalized medicine,
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43 364 expanded clinical applications, innovative delivery systems, robust regulatory frameworks, and
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45 365 integration with digital health solutions. These developments will elevate probiotics from dietary
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366 supplements to integral components of precision healthcare, offering targeted therapies for
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48 367 enhancing gut health, immune function, and metabolic well-being across diverse patient
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50 368 populations. Continued interdisciplinary research and collaboration will drive these advancements,
51
52 369 paving the way for a new era in probiotic-based therapies and preventive health strategies.
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55 370
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58 371
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Declaration of Interest Statement

Declaration of Interest Statement

The authors declare no conflicts of interest. This systematic review was conducted independently
and without any financial support or influence from commercial entities or organizations with
vested interests in the outcomes of this research. All results and conclusions presented in this
review are based on the analysis of available scientific literature and are not influenced by any
external parties.
Manuscript

Not applicable