Probiotics in The Prevention and Management of Human Diseases: A Scientific Perspective

By Mitesh Kumar Dwivedi

Probiotics in The Prevention and Management of Human Diseases: A Scientific Perspective addresses the use of probiotics and their mechanistic aspects in diverse human diseases. In particular, the mechanistic aspects of how these probiotics are involved in mitigating disease symptoms (novel approaches and immune-mechanisms induced by Probiotics), clinical trials of certain probiotics, and animal model studies will be presented through this book. In addition, the book covers the role of probiotics in prevention and management aspects of crucial human diseases, including multidrug resistant infections, hospital acquired infections, allergic conditions, autoimmune diseases, metabolic disorders, gastrointestinal diseases, neurological disorders, and cancers.

Finally, the book addresses the use of probiotics as vaccine adjuvants and as a solution for nutritional health problems and describes the challenges of using probiotics in management of human disease conditions as well as their biosafety concerns. Intended for nutrition researchers, microbiologists, physiologists, and researchers in related disciplines as well as students studying these topics require a resource that addresses the specific role of probiotics in the prevention and management of human disease.

• Contains information on the use of probiotics in significant human diseases, including antibiotic resistant microbial infections
• Presents novel applications of probiotics, including their use in vaccine adjuvants and concept of pharmabiotics
• Includes case studies and human clinical trials for probiotics in diverse disease conditions and explores the role of probiotics in mitigation of the symptoms of disease

• Language: English
• Publisher: Academic Press
• Release date: Dec 2, 2021
• ISBN: 9780128237342

Book preview

Probiotics in the Prevention and Management of Human Diseases

A Scientific Perspective

Edited by

Mitesh Kumar Dwivedi

C.G. Bhakta Institute of Biotechnology, Faculty of Science, Uka Tarsadia University, Maliba Campus, Bardoli, India

N. Amaresan

C.G. Bhakta Institute of Biotechnology, Faculty of Science, Uka Tarsadia University, Maliba Campus, Bardoli, India

A. Sankaranarayanan

Department of Life Sciences, Sri Sathya Sai University for Human Excellence, Kalaburagi, India

E. Helen Kemp

Department of Oncology and Metabolism, University of Sheffield, Sheffield, United Kingdom

Table of Contents

Cover image

Title page

Copyright

List of contributors

About the editors

Foreword

Preface

Chapter 1. The concept of probiotics, prebiotics, postbiotics, synbiotics, nutribiotics, and pharmabiotics

Abstract

1.1 Introduction

1.2 Probiotics

1.3 Prebiotics

1.4 Synbiotics

1.5 Postbiotics

1.6 Nutribiotics

1.7 Pharmabiotics

Acknowledgments

References

Chapter 2. Food or pharma: the name does make a difference

Abstract

2.1 Introduction

2.2 Probiotics: a substance or a product?

2.3 The various regulatory statuses applicable to products containing probiotics

2.4 Comparative summary

2.5 Conclusion: the name does make a difference

Conflict of interest

Notice

References

Chapter 3. The role of probiotics in maintaining immune homeostasis

Abstract

3.1 Introduction

3.2 Conlusion

Acknowledgment

References

Chapter 4. Effect of intestinal microbiome, antibiotics, and probiotics in the prevention and management of ulcerative colitis

Abstract

4.1 Introduction

4.2 The role of intestinal microbiota in the development of bowel diseases

4.3 General characteristics of drugs used in bowel diseases

4.4 Modification of intestinal microbiome

4.5 Conclusion

Acknowledgments

References

Chapter 5. Probiotics in the prevention and management of necrotizing enterocolitis

Abstract

5.1 Introduction

5.2 The microbiome, dysbiosis, and NEC

5.3 Most relevant mechanisms of probiotic action in the preterm

5.4 Probiotics and prevention of NEC

5.5 Safety aspects of probiotics

5.6 Conclusions and challenges for future research

References

Chapter 6. Probiotics in the prevention and management of irritable bowel syndrome

Abstract

6.1 Introduction

6.2 Probiotics in prevention and management of IBS

6.3 Conclusion

References

Chapter 7. Probiotics in the prevention and treatment of diarrheal disease

Abstract

7.1 Introduction

7.2 Diarrheal diseases

7.3 Probiotics in prevention and treatment of diarrheal diseases

7.4 Mode of action of probiotics

7.5 Conclusions

Acknowledgment

References

Chapter 8. Probiotics in the prevention and treatment of atopic skin diseases

Abstract

8.1 Introduction

8.2 Etiology and pathophysiology of atopic dermatitis

8.3 Relationship between gut microbiota and atopic dermatitis

8.4 Intervention of probiotics in atopic dermatitis

8.5 Future perspectives of probiotics in prevention and treatment of AD

8.6 Conclusion

Acknowledgment

References

Chapter 9. Probiotics for the treatment of other skin conditions (acne, psoriasis, seborrheic dermatitis, wounds, and skin cancer)

Abstract

9.1 Acne vulgaris

9.2 Psoriasis

9.3 Seborrheic dermatitis

9.4 Wound healing

9.5 Skin cancer

References

Chapter 10. Probiotics in the prevention and management of allergic diseases (asthma and allergic rhinitis)

abstract

10.1 Introduction

10.2 Prevention of asthma

10.3 Probiotics for the treatment of asthma

10.4 Probiotics for the prevention of allergic rhinitis

10.5 Probiotics for the treatment of allergic rhinitis

10.6 Conclusions

Acknowledgment

Funding

Conflicts of interest

References

Chapter 11. Prenatal and neonatal probiotic intake in pediatric allergy

Abstract

11.1 Introduction

11.2 Safety of probiotics and prebiotics

11.3 Probiotics, prebiotics, and immunity

11.4 Microbiota and allergic disorders

11.5 Mother’s microbiome and child health

11.6 Clinical studies

11.7 Conclusions

References

Chapter 12. Probiotics and prebiotics in the suppression of autoimmune diseases

Abstract

12.1 Introduction

12.2 Autoimmune diseases

12.3 Relationship between gut microbiota and immune system

12.4 Gut microbiota associated with autoimmune diseases

12.5 Beneficial role of probiotics in the suppression of autoimmune diseases

12.6 Future perspectives

12.7 Conclusions

Acknowledgments

Conflict of interest

References

Chapter 13. Probiotics and prebiotics in the prevention and management of human cancers (colon cancer, stomach cancer, breast cancer, and cervix cancer)

Abstract

13.1 Introduction

13.2 Probiotics and prebiotics in stomach cancer

13.3 Probiotics and prebiotics in colon cancer

13.4 Probiotics and prebiotics in breast cancer

13.5 Probiotics and prebiotics in cervical cancer

13.6 Conclusion

Acknowledgment

References

Chapter 14. Probiotics in mitigation of food allergies and lactose intolerance

Abstract

14.1 Introduction of probiotics and the gut microbiome

14.2 Food allergies and lactose intolerance

14.3 Lactose intolerance

14.4 Role of probiotics in mitigation of food allergies and lactose intolerance

14.5 Dietary management strategies

14.6 Therapeutic applications

14.7 Intake of probiotics

14.8 Future prospective of probiotic in food allergies

14.9 Conclusions

References

Chapter 15. Probiotics in the prevention and treatment of nosocomial infections

Abstract

15.1 Introduction

15.2 Hospital-acquired pneumonia and ventilator-associated pneumonia

15.3 Clostridium difficile infection

15.4 Conclusion

References

Chapter 16. Role of probiotics in urological health

Abstract

16.1 Introduction

16.2 Vaginal microbiota

16.3 Commensal microbial flora and preventing UTI

16.4 Scope of the problem

16.5 Urinary tract infection

16.6 Bacterial vaginosis

16.7 Yeast vaginitis

16.8 Modes of administration of probiotics

16.9 What does the evidence say?

16.10 Conclusion

References

Chapter 17. Role of probiotics in prevention and treatment of Candida vaginitis and Bacterial vaginosis

Abstract

17.1 Introduction

17.2 Healthy vaginal microflora and probiotic lactobacilli

17.3 Vaginitis (vaginal infection)

17.4 Probiotic roles in the prevention and treatment of vaginal infection

17.5 Conclusion

References

Chapter 18. Role of probiotics in the prevention and treatment of oral diseases

Abstract

18.1 Introduction

18.2 Role of probiotics in prevention and treatment of dental caries

18.3 Role of probiotics in the prevention and treatment of periodontal diseases

18.4 Role of probiotics in the prevention and treatment of halitosis

18.5 Conclusions

References

Chapter 19. Role of probiotics in infections with multidrug-resistant organisms

Abstract

19.1 Introduction

19.2 Probiotics

19.3 General mechanisms of actions of probiotics against MDR bacteria

19.4 Probiotics in organ-specific resistant infections

19.5 Conclusion

References

Chapter 20. Probiotics in the prevention and treatment of infections with Helicobacter pylori, Enterohemorrhagic Escherichia coli, and Rotavirus

Abstract

20.1 Introduction

20.2 Probiotics and their health implications

20.3 Infections caused by Helicobacter pylori, enterohemorrhagic Escherichia coli, and rotavirus

20.4 Helicobacter pylori

20.5 Enterohemorrhagic Escherichia coli

20.6 Rotavirus

20.7 Conclusion and future perspectives

References

Chapter 21. Role of probiotics in the management of fungal infections

Abstract

21.1 Introduction

21.2 Probiotics

21.3 Probiotics in fungal diseases

21.4 Future perspectives

21.5 Conclusions

Acknowledgment

References

Chapter 22. Role of probiotics in the prevention and management of diabetes and obesity

Abstract

22.1 Introduction

22.2 Pathophysiology and risk factors of diabetes mellitus and obesity

22.3 Probiotics for the management of diabetes and obesity

22.4 Conclusions

References

Chapter 23. Probiotics in the prevention and management of cardiovascular diseases with focus on dyslipidemia

Abstract

23.1 Introduction

23.2 Probiotic bacteria

23.3 Probiotic yeasts

23.4 Conclusion

References

Chapter 24. Gut–brain axis: role of probiotics in neurodevelopmental disorders including autism spectrum disorder

Abstract

24.1 Introduction

24.2 Colonization of the intestinal ecosystem in early life and its evolution

24.3 Gut microbiota

24.4 What are probiotics?

24.5 Psychobiotics, prebiotics, and synbiotics

24.6 Autism and probiotics

24.7 ASD and GI disorders

24.8 The gut–brain axis

24.9 Neurodevelopmental disorders

24.10 Is the gut microbiota of children with autism spectrum disorder different?

24.11 Literature evidence in ASD

24.12 Newer techniques involving microbiota

24.13 ADHD

24.14 Other neurodevelopmental disorders

24.15 Future perspectives

24.16 Conclusion

References

Chapter 25. Probiotics in the prevention and control of foodborne diseases in humans

Abstract

25.1 Introduction

25.2 Foodborne diseases

25.3 Probiotics

25.4 Antimicrobial potential of probiotics against foodborne pathogens

25.5 Probiotics mechanisms of action in the control and prevention of foodborne pathogens

25.6 Supplementation of probiotics in food materials

25.7 Delivery system of probiotics

25.8 The safety of probiotic therapy in host

25.9 Health significance of probiotics in the prevention of foodborne diseases

25.10 Conclusion and future perspectives

Acknowledgment

References

Chapter 26. Role of probiotics in the management of respiratory infections

Abstract

26.1 Introduction

26.2 Respiratory tract infections

26.3 In search of new therapeutic strategies: microbiota and gut-lung axis

26.4 Pulmonary microbiota in diseases

26.5 History of probiotics

26.6 Probiotic usage and safety

26.7 Probiotic administration in respiratory infections

26.8 Conclusion

References

Chapter 27. The role of probiotics in nutritional health: probiotics as nutribiotics

Abstract

27.1 Nutribiotics: ways to improve the nutritional status

27.2 Nutritional health benefits of probiotics and postbiotics

27.3 Encapsulation technology for the development of functional ingredients

27.4 Current market of probiotics and future perspectives

27.5 Conclusions

References

Chapter 28. Role of immunobiotic lactic acid bacteria as vaccine adjuvants

Abstract

28.1 Introduction

28.2 Vaccine adjuvants

28.3 Probiotic lactic acid bacteria

28.4 Conclusions

References

Chapter 29. Probiotics: past, present, and future challenges

Abstract

29.1 Probiotics—the concept

29.2 Probiotics—modern trends

29.3 Viability of probiotic bacteria in the gastrointestinal tract and their secondary reproduction: probiotic concentration

29.4 Dose of probiotics

29.5 Safety of probiotic bacteria

29.6 Health effects of probiotics

29.7 Probiotics and metabolic syndrome

29.8 Probiotics and urogenital infections

29.9 Probiotics and immunity

29.10 Probiotics and mental illness called Plus Ultra

29.11 The next 45 years

29.12 Summary

29.13 Probiotics and Covid-19: data supporting the use of probiotics to prevent Covid-19

29.14 Conclusion

References

Chapter 30. Probiotics: health safety considerations

Abstract

30.1 Introduction

30.2 Conclusions

Acknowledgments

Declaration of competing interest

References

Chapter 31. Probiotics: current regulatory aspects of probiotics for use in different disease conditions

Abstract

31.1 Introduction

31.2 Current regulation bodies that include probiotics

31.3 Regulations for use of probiotics in gastrointestinal diseases

31.4 Regulations for use of probiotics in diseases other than gastrointestinal diseases

31.5 Conclusions

References

Index

Copyright

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List of contributors

Adekemi Titilayo Adesulu-Dahunsi,     Food Science and Technology Programme, College of Agriculture, Engineering and Science, Bowen University, Iwo, Nigeria

Gbenga Adedeji Adewumi,     Department of Microbiology, Faculty of Science, University of Lagos, Lagos, Nigeria

Monica Rose Amarlapudi,     Molecular Biology Unit, Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, India

Chandrasekhar Balasubramaniam,     Molecular Biology Unit, Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, India

Mahmoud H. Barakat,     Faculty of Medicine, Cairo University (Al Kasr Al Ainy), Cairo, Egypt

Luis Javier R. Barrón,     Lactiker Research Group, Department of Pharmacy and Food Sciences, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain

Jorge G.S. Batista,     Energy and Nuclear Research Institute (IPEN), University of São Paulo, São Paulo, Brazil

Vladimír Bella,     Departmentof Mammology, St. Elizabeth Cancer Institute, Bratislava, Slovakia

Ankit Bharti,     Aura Skin and Dental Clinic, Tapi, India

Hemant Borase,     C. G. Bhakta Institute of Biotechnology, Uka Tarsadia University, Maliba Campus, Bardoli, India

Archana Chaudhari

Vyara Clinical Laboratory Pvt Ltd., Tapi, India

Department of Biochemistry, The Maharaja Sayajirao University of Baroda, Vadodara, India

María Chávarri,     Health and Food Area, Health Division, TECNALIA, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Álava, Miñano, Spain

Michelle W. Cheng,     Division of Dermatology and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States

Magali Cordaillat-Simmons,     Pharmabiotic Research Institute (PRI), Narbonne, France

Maryam Dadar,     Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran

Nilanjana Das,     Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore, India

Charlotte De Geyter,     Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium

María del Carmen Villarán,     Health and Food Area, Health Division, TECNALIA, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Álava, Miñano, Spain

Lucía Diez-Gutiérrez,     Health and Food Area, Health Division, TECNALIA, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Álava, Miñano, Spain

Mitesh Kumar Dwivedi,     C.G. Bhakta Institute of Biotechnology, Faculty of Science, Uka Tarsadia University, Maliba Campus, Bardoli, India

Alejandro Egea-Zorrilla,     Laboratory of Cardiovascular Development and Disease, Andalusian Centre for Nanomedicine and Biotechnology (Bionand), Technological Park of Andalusia C/ Severo Ochoa, Málaga, Spain

Ahmed M. El Hamaky,     Mycology department, Animal Health Research Institute (AHRI), Agriculture Research Center (ARC), Giza, Egypt

Elizabethe Adriana Esteves

Graduate Program in Nutrition Sciences, Faculty of Biological and Health Sciences/Federal University of Jequitinhonha and Mucuri Valeys, Diamantina, Brazil

Graduate Program in Health Sciences, Faculty of Biological and Health Sciences/Federal University of Jequitinhonha and Mucuri Valeys, Diamantina, Brazil

Aryel H. Ferreira,     Energy and Nuclear Research Institute (IPEN), University of São Paulo, São Paulo, Brazil

Sabina Fijan,     University of Maribor, Faculty of Health Sciences, Institute for Health and Nutrition, Maribor, Slovenia

Ana C.M. Fonseca,     Virtual University of the State of Sao Paulo (UNIVESP), São Paulo, Brazil

Lucas F. Freitas,     Energy and Nuclear Research Institute (IPEN), University of São Paulo, São Paulo, Brazil

Kaloyan Georgiev,     Department of Pharmacology, Toxicology and Pharmacotherapy, Faculty of Pharmacy, Medical University of Varna, Varna, Bulgaria

Marieta Georgieva,     Department of Pharmacology, Toxicology and Pharmacotherapy, Faculty of Pharmacy, Medical University of Varna, Varna, Bulgaria

Prashant S. Giri,     C.G. Bhakta Institute of Biotechnology, Faculty of Science, Uka Tarsadia University, Maliba Campus, Bardoli, India

Sunita Grover,     Molecular Biology Unit, Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, India

Sheffali Gulati,     Center of Excellence and Advanced Research for Childhood Neurodevelopmental Disorders, Child Neurology Division, Department of Pediatrics, AIIMS, New Delhi, India

Atef A. Hassan,     Mycology department, Animal Health Research Institute (AHRI), Agriculture Research Center (ARC), Giza, Egypt

Bruno Hauser,     Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium

Nadezhda Hvarchanova,     Department of Pharmacology, Toxicology and Pharmacotherapy, Faculty of Pharmacy, Medical University of Varna, Varna, Bulgaria

Josef Jampílek

Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia

Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia

Rushikesh G. Joshi,     Department of Biochemistry and Forensic Science, University School of Sciences, Gujarat University, Ahmedabad, India

Saurabh Kadyan,     Molecular Biology Unit, Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, India

Julie Kalabalik-Hoganson,     School of Pharmacy and Health Sciences, Fairleigh Dickinson University, Florham Park, NJ, United States

Shweta Kelkar,     Molecular Biology Unit, Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, India

Devang Bharatkumar Khambholja,     P.G. Department of Medical Technology, B.N. Patel Institute of Paramedical and Science (Paramedical Division), Anand, India

Aruna Jyothi Kora

National Centre for Compositional Characterisation of Materials (NCCCM), Bhabha Atomic Research Centre (BARC), ECIL PO, Hyderabad, India

Homi Bhabha National Institute (HBNI), Mumbai, India

Katarína Kráľová,     Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia

Ramar Krishnamurthy,     C. G. Bhakta Institute of Biotechnology, Uka Tarsadia University, Maliba Campus, Bardoli, India

Prasant Kumar,     Ingress Bio-Solutions Pvt Ltd, Ahmedabad, India

Ivan Kushkevych,     Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic

Elvira Ingrid Levy,     Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium

Caroline S.A. Lima,     Energy and Nuclear Research Institute (IPEN), University of São Paulo, São Paulo, Brazil

Ademar B. Lugão,     Energy and Nuclear Research Institute (IPEN), University of São Paulo, São Paulo, Brazil

Rashmi Hogarehalli Mallappa,     Molecular Biology Unit, Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, India

Sanjeeb Kumar Mandal,     Sri Shakthi Institute of Engineering and Technology, Coimbatore, India

Ranjith Kumar Manokaran,     Center of Excellence and Advanced Research for Childhood Neurodevelopmental Disorders, Child Neurology Division, Department of Pediatrics, AIIMS, New Delhi, India

Izaskun Marañón,     Health and Food Area, Health Division, TECNALIA, Basque Research and Technology Alliance (BRTA), Parque Tecnológico de Álava, Miñano, Spain

Lien Meirlaen,     Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium

Cristina Méndez-Malagón,     Center of Biomedical Research, University of Granada, Granada, Spain

Shireen Mentor,     Department of Medical Biosciences, University of the Western Cape, Cape Town, South Africa

Dušanka Mičeti-Turk

University of Maribor, Faculty of Medicine, Maribor, Slovenia

University of Maribor, Faculty of Health Sciences, Institute for Health and Nutrition, Maribor, Slovenia

Naheed Mojgani,     Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran

Lauane Gomes Moreno,     Multicentre Graduate Program in Physiological Sciences, Faculty of Biological and Health Sciences/Federal University of Jequitinhonha and Mucuri Valeys, Diamantina, Brazil

Basavaprabhu Haranahalli Nataraj,     Molecular Biology Unit, Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, India

Kamila M. Nogueira,     Energy and Nuclear Research Institute (IPEN), University of São Paulo, São Paulo, Brazil

Noha H. Oraby,     Mycology department, Animal Health Research Institute (AHRI), Agriculture Research Center (ARC), Giza, Egypt

Elif Özdener-Poyraz,     School of Pharmacy and Health Sciences, Fairleigh Dickinson University, Florham Park, NJ, United States

Hiteshkumar V. Patel,     Department of Biochemistry, Shri A.N. Patel PG Institute of Science and Research, Anand, India

Satish Patil,     School of Life Sciences, Kavayitri Bahinabai Chaudhari North Maharashtra University, Jalgaon, India

Pedro Perez-Ferrer,     Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, Merced, CA, United States

Julio Plaza-Diaz,     Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada

Maja Šiki Pogačar,     University of Maribor, Faculty of Medicine, Maribor, Slovenia

Bruno Pot

Pharmabiotic Research Institute (PRI), Narbonne, France

Research Group of Industrial Microbiology and Food Biotechnology (IMDO), Vrije Universiteit Brussel (Free University Brussels), Elsene, Belgium

Diwas Pradhan,     Molecular Biology Unit, Dairy Microbiology Division, ICAR-National Dairy Research Institute, Karnal, India

Rodrigo Pereira Prates,     Multicentre Graduate Program in Physiological Sciences, Faculty of Biological and Health Sciences/Federal University of Jequitinhonha and Mucuri Valeys, Diamantina, Brazil

Mangala Lakshmi Ragavan,     Department of Biomedical Sciences, School of Bio Sciences and Technology, Vellore, India

Cíntia Lacerda Ramos

Graduate Program in Nutrition Sciences, Faculty of Biological and Health Sciences/Federal University of Jequitinhonha and Mucuri Valeys, Diamantina, Brazil

Graduate Program in Health Sciences, Faculty of Biological and Health Sciences/Federal University of Jequitinhonha and Mucuri Valeys, Diamantina, Brazil

Adriana S. Rodrigues,     Energy and Nuclear Research Institute (IPEN), University of São Paulo, São Paulo, Brazil

Alice Rouanet,     Pharmabiotic Research Institute (PRI), Narbonne, France

Sophia Sangar,     Division of Dermatology and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States

Carina Sousa Santos,     Graduate Program in Nutrition Sciences, Faculty of Biological and Health Sciences/Federal University of Jequitinhonha and Mucuri Valeys, Diamantina, Brazil

Rasha M.H. Sayed-ElAhl,     Mycology department, Animal Health Research Institute (AHRI), Agriculture Research Center (ARC), Giza, Egypt

Eleonora Seghesio,     Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium

Firdosh Shah,     C.G. Bhakta Institute of Biotechnology, Faculty of Science, Uka Tarsadia University, Maliba Campus, Bardoli, India

Youcef Shahali

Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran

The University Hospital of Besançon, Besançon, France

Malgorzata Slugocki,     School of Pharmacy and Health Sciences, Fairleigh Dickinson University, Florham Park, NJ, United States

Velaphi C. Thipe,     Energy and Nuclear Research Institute (IPEN), University of São Paulo, São Paulo, Brazil

Bhuvan Shankar Vadala,     Sri Venkateswara University, Tirupati, India

Yvan Vandenplas,     Vrije Universiteit Brussel (VUB), UZ Brussel, KidZ Health Castle, Brussels, Belgium

Santosh S. Waigankar,     Kokilaben Dhirubhai Ambani Hospital, Mumbai, India

Yang Yu,     Division of Dermatology and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States

About the editors

Dr. Mitesh Kumar Dwivedi is an assistant professor of microbiology at C.G. Bhakta Institute of Biotechnology, Uka Tarsadia University. He has published 54 research papers in reputed journals, written 16 book chapters, and is the editor of 6 books. He has an h-index of 21 with 1603 citations for his research papers. He has more than 14 years of experience in research and teaching in various allied fields of microbiology and immunology. His research areas include autoimmunity, probiotics in human health and disease, host–microbe interaction, and immunogenetics of human diseases. He has been serving as an editorial board member and reviewer of many international journals. He has been honored with many international and national awards for his excellent research performance [Best Researcher Award (2020), INSA Visiting Scientist Award (2019), DST-SERB Early Career Research Award (2018), Young Scientist Awards (2011, 2013, and 2018)] and secured all India rank 32 in CSIR-NET National examination (2011; Life Sciences). He has successfully completed research projects from national funding agencies such as SERB-DST, GUJCOST, UTU, and Neosciences & Research Solutions Pvt. Ltd. and guided students for their doctoral and master degrees.

Dr. N. Amaresan is an assistant professor at C.G. Bhakta Institute of Biotechnology, Uka Tarsadia University, Gujarat. He has over 15 years of experience in teaching and research in various allied fields of microbiology. He has been awarded the Young Scientist Awards by the Association of Microbiologists of India and the National Academy of Biological Sciences. He was also awarded visiting scientist fellowship from the National Academy of India. He has published more than 100 research articles, book chapters, and books of national and international repute. He also deposited over 550 16S rDNA, 28S rDNA, and ITS rDNA sequences in the Genbank (NCBI, EMBL, and DDBJ) and also preserved over 150 microbial germplasm in various culture collection centers of India. He has successfully completed research projects from national funding agencies such as SERB-DST, GUJCOST, UTU, and GEMI and guided students for their doctoral and master’s degrees.

Dr. A. Sankaranarayanan is an associate professor in the Department of Life Sciences, Sri Sathya Sai University for Human Excellence, Kalaburagi, Karnataka, India from June 2021 onward. His current research focus is on fermented food products. He has published 8 books, 30 chapters, 60 research articles in international and national journals of repute; guided 5 Ph.D., and 16 M.Phil., scholars; and operated 5 minor funded projects in Microbiology. From 2002–15, he worked as an assistant professor and head in the Department of Microbiology, K.S.R. College of Arts & Science, Tiruchengode, Tamil Nadu, and from August 2015 to May 2021, he was associated with Uka Tarsadia University, Surat, Gujarat, India. He has been awarded Indian Academy of Sciences (IASc), National Academy of Sciences (NAS), and The National Academy of Sciences (TNAS) sponsored summer research fellowship for young teachers consecutively for 3 years and his name is included as a mentor in DST-Mentors/Resource persons for summer/winter camps and other INSPIRE initiatives, Department of Science & Technology, Govt. of India, New Delhi. He is a grant reviewer in the British Society of Antimicrobial Chemotherapy (BSAC), United Kingdom.

Dr. E. Helen Kemp completed her Ph.D. in microbiology at the University of Warwick and the Centre for Applied Microbiology and Research, Salisbury, in 1988. Since 1989, she has worked at the University of Sheffield as a Postdoctoral Research Fellow in the Department of Molecular Biology and Biotechnology and then in the Department of Oncology and Metabolism. She has long-standing interests in the autoimmune and genetic aspects of the depigmenting disease vitiligo, characterizing autoimmune responses against the calcium-sensing receptor in patients with parathyroid autoimmunity, and the etiology of autoimmune thyroid disease. She has published more than 70 research papers on all these areas of research and has contributed to books and review articles.

Foreword

Dear Reader,

When I became aware of a book being prepared entitled Probiotics in the Prevention and Management of Human Diseases: A Scientific Perspective, I became really interested! Probiotics have a long history in foods that, by their WHO/FAO definition, exert health benefits. In the past, these health benefits rarely covered real treatment approaches for human diseases, at least not in a way known for traditional drugs. I saw this book as an opportunity to pull the focus toward a different intended use for probiotics: prevent or cure disease!

The huge progress in sequencing and metabolomic technology overwhelmingly showed the impact of the (gut) microbiota in the development of human disease, beyond microbiota quality or functionality, such as mood, anxiety, and autism spectrum disorder. The logical, but maybe unfortunate, consequence of this was the fact that expectations for foods were raised to a prophylactic and even therapeutic level! While there is of course nothing wrong with foods contributing to health, expectations for probiotics were no longer at the food level, and the initial absence of drug results tended to impact negatively on the use of probiotics for both types of applications.

So when the opportunity to contribute to this book came along, I was really excited. It indeed turned out to be a wonderful occasion to clarify and realistically discuss the broad application pallet of probiotics in different fields of medicine. Interestingly, these applications were often those where traditional drugs, because of side effects, can offer only short-term successes or are in the field of noncommunicable diseases, which are putting a huge burden on our current and future health care system and for which often no adequate drug solutions are available. This book shall explain that drugs are not the same as foods in terms of strain selection, clinical research strategy, intended use, or manufacturing. For that particular reason, I am very grateful to the editors to have considered chapters on regulatory differences between foods and pharma, and their efforts to clarify the concepts of prebiotics, postbiotics, synbiotics, nutribiotics, and pharmabiotics, besides probiotics. Without any doubt, this may contribute to a more correct use of the terms, help reduce confusion for both doctors and their patients, and define clear health benefits of the biotic family.

So here it is, a book on probiotics in medicine. Whether you are interested in how probiotics interact with the immune system, how to use probiotics in early life such as preterm infants and through the life stages, or wonder if there are specific strains for specific applications, you may find some of the answers here. The book is organized around at least 25 possible disease topics but will also try to answer current safety questions as well as highlight challenges for the probiotics of the future.

Having a keen interest in probiotics for almost 35 years as a food microbiologist, I have always welcomed the wider, medical interest in these wonderful microorganisms, but at the same time got slightly concerned about expectations that went far beyond the wildest of our scientific dreams. It is my sincere hope that this book will contribute to a better, realistic understanding of where probiotics could support, sometimes replace, and in some cases excel traditional drugs. The timing for the book is definitely right, the setting too, now it is only up to you to enjoy!

Bruno Pot is the Science Director Europe for Yakult; the Pharmabiotics Research Institute’s president; a member of the Taxonomic Subcommittee for Lactobacilli, Bifidobacteria, and related taxa; and a teacher of courses in food microbiology and food hygiene at the Vrije Universiteit Brussels.

Bruno Pot¹,², ¹Yakult Europe Science Department, Almere, The Netherlands, ²Vrije Universiteit Brussel, Research Group of Industrial Microbiology and Food Biotechnology (IMDO), Elsene, Belgium

Preface

Mitesh Kumar Dwivedi, N. Amaresan, A. Sankaranarayanan and E. Helen Kemp

Probiotics, a rapidly emerging field during the past three decades, continues to gain ground with applications in various fields, especially in human health. According to FAO and WHO reports, live microorganisms, which are administered in sufficient amounts to provide beneficial health to their host, are considered as Probiotics. They can have beneficial and potentially therapeutic effects through their antimicrobial and immune-modulatory activities.

The major focus of this book is to highlight the current and future use of probiotics in different human diseases as addressed by relevant research studies, clinical case studies, and animal models. Probiotics are diverse, so there is a need to explain in depth their mechanism of action and to give an update on research especially in the area of human disease. Hence, the book presents invited chapters from experts in the field of probiotic research on the prevention and management of various human diseases such as life-threatening cancers, immune-mediated conditions, and infectious diseases, including the emerging multidrug-resistant infections. Collectively 31 chapters cover the basic concepts of probiotics as well as current research into their effects on human disease including cardiovascular, neurological, respiratory, allergic, autoimmune, metabolic, and diarrheal diseases as well as human cancers especially of the colon, stomach, breast, and cervix. In addition, the book addresses the novel concept of probiotics as a vaccine adjuvant and as a solution for nutritional health problems. Along with this, the chapters also deal with the current challenges and health-safety concerns in using probiotics, biosafety measures, and various regulatory aspects of probiotic usage in different disease conditions.

We, the editorial team, strongly believe that this book will be used for education and as a scientific tool among academics, clinicians, scientists, young researchers, and health professionals, as well as graduate and postgraduate students.

As the editors of this book, we would like to express our sincere gratitude to all authors for their excellent contributions to this book. We are also indebted to the publishers for all their efforts to bring out the book in a timely manner. Healthy criticism and comments are always welcome.

Chapter 1

The concept of probiotics, prebiotics, postbiotics, synbiotics, nutribiotics, and pharmabiotics

Archana Chaudhari¹ and Mitesh Kumar Dwivedi²,    ¹Department of Biochemistry, The Maharaja Sayajirao University of Baroda, Vadodara, India,    ²C.G. Bhakta Institute of Biotechnology, Faculty of Science, Uka Tarsadia University, Maliba Campus, Bardoli, India

Abstract

The composition of intestinal microflora plays an important role in human health as alteration in the gut microflora gives rise to various pathological diseases. This chapter discusses the concept of probiotics and prebiotics as well as the new emerging definitions being added to probiotic terminology, such as postbiotics, nutribiotics, and pharmabiotics. Probiotics are live microorganisms that when administered in adequate amounts confer a health benefit on the host microbes. The prebiotics act as foods for probiotics and provide health and physiological benefits to the host. Synbiotics are next-generation probiotics made with various formulations of probiotics and prebiotics that work in synergism to reestablish the healthy gut ecology. The postbiotics are soluble products or metabolic by-products secreted by live bacteria or released after bacterial lysis that offer health benefits to the host. They are relatively safer as they lack serious side effects as compared to probiotics. Nutribiotics are probiotics that confer nutritional functions by producing essential nutrients, such as vitamins and minerals, and converting precursors to bioactive metabolites. Pharmabiotics are probiotic products with a proven pharmacological action in health or disease.

Keywords

Gut microflora; probiotics; prebiotics; synbiotic; postbiotics; nutribiotics; pharmabiotics

1.1 Introduction

Human health is slowly deteriorating due to the inclination toward sedentary lifestyle of people, decrease in the consumption of home-cooked foods along with rise in the consumption of poor-quality food (Christmann, 2020). This has also affected the qualitative and quantitative composition of the intestinal microbiota, which correlates with various pathological disorders. Bioactive components, such as probiotics, prebiotics, and synbiotics, have provided a new hope to human health by restoring microbial imbalance and have come out as a nonharmful cure to painful diseases, thereby improving well-being and preventing complications (Fujiya et al., 2014; Maslennikov et al., 2018; Shen et al., 2017). As a result, there is rise in interest on the consumption of food products containing bioactive components that enhance the nutritive value (Pandey et al., 2015). This chapter is focused to provide the conceptual basis of different emerging terminologies used in the probiotic field (Fig. 1.1).

Figure 1.1 Different terminologies related to probiotics.

1.2 Probiotics

The modern history of probiotics starts with the pioneering studies of Russian scientist Elie Metchnikoff in 1907, who first created the foundation of the concept of beneficial microorganisms that today we know as probiotics. He studied the effect of consumption of fermented products, such as yogurt, on human health, thereby associating it with the long-life expectancy of Bulgarian people (Mackowiak, 2013). He also specified that the dependence of the intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes. This clearly states the probiotic concept. He considered the Lactobacilli as probiotic that could have a positive influence on health and prevent aging. Since then the precise definition of probiotic has evolved according to the development of probiotic concept. Werner Kollath in 1953 first developed the term probiotics for active substances that are essential for healthy development of life (Gasbarrini et al., 2016). In 1965 Lilly and Stillwell determined that a microorganism secrets some growth stimulators for another microorganism (Lilly & Stillwell, 1965). This positive effect may cause the application of the term probiotic for these kinds of microorganisms. The term probiotic was first used by Parker for the definition of substances and organisms, which cause the microbial balance in the gastrointestinal tract (Parker, 1974). And there were also other researchers in between who had their own different definition for probiotic. Finally, in 2014 the International Scientific Association for Probiotics and Prebiotics (ISAPP) defined probiotics as live microorganisms, that when administered in adequate amounts, confer a health benefit on the host (Hill et al., 2014). From that time on, this definition has been widely used by scientific community (Fig. 1.2).

Figure 1.2 Evolution of the term probiotics.

Probiotics have been isolated from various sites, such as gut and traditional fermented foods. They mostly belong to genera Lactobacillus and Bifidobacterium, although there are also some members of Bacillus and Escherichia coli for bacteria and the yeast Saccharomyces among others. Table 1.1 shows currently used microorganisms as probiotics.

Table 1.1

Many researchers have shown the use of probiotics in a wide variety of fields. Various studies in probiotics support the fact that probiotics are useful for the eradication of antibiotic resistance by fecal transplantation to decolonize naturally resistant bacterial strains (Crum-Cianflone et al., 2015; Millan et al., 2016). Probiotics have also been shown to play an important role in psychopathology, as studies indicate that administration of probiotics is associated with a decrease in anxiety (Bravo et al., 2011). Application of probiotics has been shown to improve the acne by reducing skin colonization, improving atopic dermatitis, aging skin, and healing burns and scars (Bowe & Logan, 2011; Krutmann, 2012). Apart from this, oral supplementation of probiotics could improve skin health by a gut–brain–skin axis reducing systemic and brain inflammation and improving nutrient absorption, which favors barrier synthesis. Probiotics also play an important role in pharmacological therapies, such as immunotherapy in patients with advanced melanoma, and reducing the side effects of therapeutics (Gopalakrishnan et al., 2018; Guthrie et al., 2017).

1.3 Prebiotics

Glenn Gibson and Marcel Roberfroid first acknowledged prebiotics in 1995 and defined the old but still valid definition of prebiotics as a nonviable food component that confers a health benefit on the host associated with modulation of the microbiota (Gibson & Roberfroid, 1995; Pineiro et al., 2008). According to this definition, only a few compounds of the carbohydrate group, such as short- and long-chain β-fructans [fructo-oligosaccharides (FOSs) and inulin], lactulose, and galacto-oligosaccharide (GOS), can be classified as prebiotics. The 6th Meeting of the ISAPP in 2008 defined dietary prebiotics as a selectively fermented ingredient that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health (Gibson & Roberfroid, 1995). However, in 2017 experts of the ISAPP described the prebiotic as a substrate that is selectively utilized by host microorganisms conferring a health benefit (Fig. 1.3; Gibson et al., 2017). The current definition of prebiotics comprises of substances, such as polyphenols and polyunsaturated fatty acids, converted to their respective conjugated fatty acids together with some peptides catabolized by bacteria into active ingredients apart from carbohydrate-based prebiotics. The definition requires documented beneficial health effects of potential prebiotics. Apart from this, the updated definition includes a variety of organic and inorganic substances (i.e., micronutrients necessary for the development of bacteria) used externally and internally stimulating microorganisms not only in the GI tract but also in all niches of the body, including skin, urinary tract, and vagina (Gibson et al., 2017; Tomasik & Tomasik, 2020).

Figure 1.3 Evolution of term prebiotic.

There are many types of prebiotics mainly identified as inulin and subset of carbohydrate groups, mostly oligosaccharides. Oligosaccharides are further grouped into FOSs and GOSs. The most popular and widely used prebiotics include fructans, inulin, FOS, and GOS, which are generally regarded as safe (Ambalam et al., 2016; Kumar et al., 2015). Table 1.2 shows currently used different prebiotics and their sources.

Table 1.2

Prebiotics have been gaining a great deal of attention in recent years as they provide nutritional benefit along with health and physiological benefits. Benefits of prebiotics upon health are constantly evolving; however, until now prebiotics have been shown to be beneficial for gastrointestinal tract (pathogens’ inhibition or immune response stimulation), cardio metabolism (reduction of lipid levels in blood, effects on insulin resistance), mental health (metabolites with influence on brain function, energy, and cognition), bones (minerals bioavailability), skin (hydration of surface layers of the skin and normalizes its keratinization and exfoliation), and urogenital tract (reduces the level of toxins in chronic kidney diseases). They also play an important role in the reduction of metabolic diseases, such as obesity, type 1 and type 2 diabetes, and nonalcoholic fatty liver disease.

1.4 Synbiotics

Different probiotic strains require different food sources to live according to the need whereby only a single strain will be able to utilize a particular food source and remaining strains will decrease. The researchers in early 1960s had noticed the potential of synbiotics in the field of nutrition to interfere with the human intestinal microbiota (Turek, 1960). Prebiotics are utilized for the most part as a particular vehicle for the development of a probiotic strain and maturation in intestinal section. Because of the utilization of prebiotics, probiotic microorganisms secure higher resistance to ecological conditions, such as oxygenation, pH, and temperature, in the digestive tract of a specific organism. Together, synbiotics support to reestablish a healthy ecology of microflora within the gastrointestinal tract by strategically combining probiotics with prebiotics, which encourages a more profound effect on gastrointestinal ecology than probiotics or prebiotics alone. Hence, the synbiotic can be defined as, A supplement that contains both a prebiotic and a probiotic that work together to promote ‘healthy microflora’ in the human intestine. Synbiotics are next generation of probiotics. Since synbiotic refers to synergism, it should be reserved for products in which the prebiotic component selectively favors the probiotic compound (Mishra et al., 2018). Table 1.3 presents few examples of synbiotics wherein the probiotics and the respective prebiotics are shown.

Table 1.3

Furthermore, the combination of probiotics with prebiotics brings about development of beneficial microbiota, the equilibrium of the metabolic movement in the gastrointestinal tract maintaining the intestinal structure and preventing the development of potential pathogens present in the intestinal tract (Goyal & Rastogi, 2020). In synbiotics, the probiotics use the prebiotics as a food source, which enables them to survive for an extended period within the intestine. The improvement in the viability of probiotics facilitates in delivering projected health benefits. These consequences increase the count of Lactobacillus and Bifidobacterium genera and maintain the balance of intestinal microflora. The synbiotics help to reduce undesired concentration of metabolites, including nitrosamines, to inactivate carcinogens and prevent constipation and diarrhea from various etiologies (Wasilewski et al., 2015). Their utilization prompts a huge increment in levels of short-chain unsaturated fats, ketones, carbon disulfides, and methyl acetic acid derivations, which possibly brings about a beneficial outcome on the host's well-being (Markowiak & Śliżewska, 2017).

1.5 Postbiotics

The research in recent years has revealed that dead or inactivated cells, cell extracts, and the cell metabolites could render significant health benefits on human (Di Lena et al., 2015). On the other hand, it is worth to mention that using living cells in some special cases might have an adverse effect on the health. For example, the administration of living probiotic cells to host with weak immune system increased the inflammatory responses (Kothari et al., 2019). Current knowledge allows stating that bacterial viability is not necessary to attain all probiotic effects, as not all mechanisms nor clinical benefits are directly related to viable bacteria (Cuevas-González et al., 2020). This was demonstrated recently, since few researchers have compared viable or inactivated microorganisms and different microbial fractions obtained from them. Research also indicates that bacterial viability is not a critical requirement for imparting health benefits and hence new terms, such as postbiotics, were created to denote the health benefits beyond the inherent viability of probiotics, providing a broader context to the probiotic concept. The concept of postbiotics is built up on the observation that the positive effects of the microflora are facilitated by the secretion of several metabolites. Postbiotics, also known as metabiotics are soluble factors secreted by live bacteria or released after bacterial lysis which confer physiological benefits to the host (Schönfeld & Wojtczak, 2016). Most common types of postbiotics are SCFA, peptides, enzymes, teichoic acids, and vitamins (Moreno-Navarrete et al., 2018). While postbiotics do not comprise live microbes, they show a valuable health outcome through the similar mechanisms that are representative of probiotics while minimizing the risks related to their intake. So, similar to prebiotics, postbiotics appear to lack serious side effects while keeping similar efficacy to probiotics. Overall, the probiotics present in a viable state can produce postbiotics. The postbiotic is also defined as cell-free supernatants, biogenics, metabolites, and metabolic waste of activity of probiotic. In 2013 Tsilingiri defined postbiotic as any effects obtained from metabolites of probiotics or any extracted or secreted molecule that offers health benefits to the host directly or indirectly (Tsilingiri & Rescigno, 2013). These soluble compounds include enzymes, exo and endo polysaccharides, surface proteins, vitamins, organic acids, fatty acids, and peptides (Aguilar-Toalá et al., 2018; Malashree et al., 2019; Tsilingiri & Rescigno, 2013). Table 1.4 lists out the different groups of postbiotics with certain examples.

Table 1.4

The production methods of postbiotics involve cell rupture by heat, enzymatic, ultrasound, or solvent treatments. After extraction, cleaning steps are needed, which can be performed by centrifugation, dialysis, lyophilization, and column purification. The postbiotics may be classified into distinct categories according to the observed physiological benefits (antiinflammatory, antioxidant, antihypertensive, antiproliferative, antimicrobial, hypocholesterolemic, and immunomodulatory activities) or by their composition, which can be derived from both bacterial cell compounds and microbial action (synthesis of metabolites and products from microbial enzymatic activity over the food matrix) (Aguilar-Toalá et al., 2018; Collado et al., 2019). Postbiotics can include bacterial lysates with cell surface proteins, bacterial enzymes and peptides, metabolites produced by bacteria, such as teichoic acids, peptidoglycan-derived neuropeptides, polysaccharides, and lower organic acids, for instance, lactic acid. Table 1.5 shows different postbiotics and respective microbial sources.

Table 1.5

Thus many health-beneficial effects acquired through the consumption of fermented foods are associated to postbiotics since they are related not only to the ingested live microorganisms but also to the microbial structures and metabolites produced during fermentation. Moreover, postbiotics can stimulate the immunological system, likely involving bowel and intestine developing antiinflammatory, immunomodulatory, antiobesogenic, antihypertensive, antiproliferative, antioxidative, and hypocholesterolemic activity (Tomasik & Tomasik, 2020). In addition, a rise in the B vitamin content in cereal grains is another remarkable case of postbiotic fermentation.

Probiotics are considered health-promoting microbes for a range of diseases throughout the human body from the gut to nonintestinal body sites, such as brain and skin (Bowe & Logan, 2011). Accordingly, the probiotics used currently are administered not only through oral delivery but are also applied on skin for burn injury and cosmetic purposes (Huseini et al., 2012; Simmering & Breves, 2010). The classical definition of probiotics covers a broad range of probiotics in foods and medicine. However, this current categorization is vague and the differences between functional foods, medicinal foods, or pharmaceutical medicine are unclear, making proper regulation difficult (Arora & Baldi, 2015). Arora and Baldi from India suggested a new categorization of probiotics as nutribiotics and pharmabiotics.

1.6 Nutribiotics

Nutribiotics can be in the forms of a food, a food product, or a dietary supplement, which are subjected to regulatory requirements related to food safety and dietary guidelines. Specific microbial groups exhibit probiotic effects on nutritional functions by producing essential nutrients, such as vitamins and minerals, converting precursors to bioactive metabolites, or relieving health problems related to nutritional status or metabolism (Vandenplas et al., 2015).

There are various probiotics that are classified as nutribiotics and used for their nutraceutic functionalities. Some microbial groups produce vitamins and contribute to the availability of vitamins in the human host. These vitamins are synthesized by the gut microbiota (LeBlanc et al., 2013), and thus the nutritional requirement for individuals with low intake of these vitamins that are not synthesized in the human body and not consumed through the diet depends on gut microbial production. Ingestion of nutribiotics may improve the vitamin status, increasing their availability in the gut (Pompei et al., 2007). Various studies have claimed to improve vitamin status of riboflavin, folate, etc. (Lin & Young, 2000; Thakur & Tomar, 2015). Nutribiotics have also been claimed to be useful for lactose intolerance, a nutritional health problem with a prevalence of approximately 70% in some regions of the Mediterranean area (Corgneau et al., 2017; Roškar et al., 2017). Research has also claimed the use of nutribiotics in the production of health-beneficial metabolites, such as conjugated linoleic acid (Kim et al., 2015). Table 1.6 presents few examples of nutribiotics.

Table 1.6

1.7 Pharmabiotics

Colin Hill from University of College Cork, Ireland, for the first time used the term pharmabiotics in 2002, during his work with Irish government-funded collaborative groups studying probiotics, led by Fergus Shanahan (Hill, 2010). The term probiotics fit into bigger category pharmabiotics, defined as bacterial cells of human origin, or their products, with a proven pharmacological role in health or disease. The pharmabiotics were suggested to include pharmaceutic probiotics with specific health claims, which may show beneficial physiological effects on body functions or play a pharmacological role in disease (Hill, 2010; Sreeja & Prajapati, 2013). Table 1.7 presents few examples of pharmabiotics. The term pharmabiotics encompasses the wide potential use of microbes that are alive or dead, the components of organisms, or metabolites of microbes (Shanahan, 2010) that are not covered by the classical definition of probiotics by the FAO/WHO. Thus the term pharmabiotics is not just limited to live microorganisms but contain probiotics, bacteriocins, bacteriophages, and bioactive molecules. Therapeutic pharmabiotics have been studied for various categories of diseases, typically gastrointestinal diseases, such as infectious diarrhea, inflammatory bowel diseases, and metabolic diseases, including obesity and diabetes (Lee et al., 2018). The representative fields of pharmabiotics include postbiotics, paraprobiotics, and probioceuticals (probiotaceuticals) (Sreeja & Prajapati, 2013).

Table 1.7

The term paraprobiotics was proposed by Taverniti and Guglielmetti (2011). They are also known as ghosts or inactivated probiotics that are defined as nonviable microbial cells (ruptured or intact) or raw cellular extracts (with complex chemical composition), which when administered (topically or orally) in adequate amounts, confer a benefit on the human or animal consumer. In particular, paraprobiotics constitutes inactivated/dead/nonviable microbial cells or cell components of probiotic cells that can be intact or ruptured upon lysis. Few examples included in the list are teichoic acids, peptidoglycan-derived muropeptides, surface protruding molecules (pili, fimbriae, flagella), polysaccharides, such as exopolysaccharides, cell surface-associated proteins, and cell wall-bound biosurfactants (Shenderov, 2013; Singh et al., 2018). Moreover, paraprobiotics are microorganisms that had its viability compromised after being submitted to processes that have induced structural and metabolic changes to the bacterial cells (de Almada et al., 2016). Paraprobiotics and postbiotics provide immunomodulatory activity to the host and are a safer alternative when the use of live probiotic bacteria is not indicated, for example, in the case of immunodeficient individuals, such as seniors and transplanted or premature newborns. The use of paraprobiotics and postbiotics in aforementioned cases reduces the risks of: (1) development of opportunistic infections; (2) increased inflammatory responses to vaccine or allergens; (3) deleterious metabolic effects due to the degradation of mucine and production of deconjugated bile salts and D-lactate, which can cause gastrointestinal disorders; (4) horizontal transfer of antibiotic resistance genes to other commensals or pathogenic bacteria in the gut; and (5) microbial translocation. In addition, paraprobiotics and postbiotics do not lose bioactivity when administered together with antibacterial and antifungal agents (Aguilar-Toalá et al., 2018; Deshpande et al., 2018; Zawistowska-Rojek & Tyski, 2018).

The term probioceuticals (probiotaceuticals) refers to probiotic-derived factors which inhibit the growth of microorganisms or other infectious organisms (yeast, molds, protozoa, viruses) (Howarth, 2010). Probiotic-derived factors include products (proteinaceous molecules, carbohydrates, and cell wall components) and metabolites (short-chain fatty acids) that exert health-promoting effects on host contributing to the reinforcement of intestinal barrier function and stimulating antiinflammatory immune responses, leading to the amelioration of intestinal inflammatory disorders (Yan & Polk, 2020). Probiotic-derived factors, for example, reuterin from Lactobacillus reuteri, have been described to inhibit the viability and adhesion of known enteric pathogens, signifying that probiotic supernatants could be a rich source of new antipathogenic compounds. Table 1.7 presents few examples of pharmabiotics with specific health claims.

In this chapter, our goal was to discuss the emerging terms in the expanding field of probiotics during the recent years. Our aim was to shed light on the differences among all the definitions to allow a clear understanding among scientific community and general public.

Acknowledgments

We are grateful to Uka Tarsadia University, Maliba Campus, Tarsadi, Gujarat, India, for providing the facilities needed for the preparation of this book chapter.

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