Nutrition and Functional Foods in Boosting Digestion, Metabolism and Immune Health

By Debasis Bagchi

Nutrition and Functional Foods in Boosting Digestion, Metabolism and Immune Health explores the role of appropriate nutrition and digestive enzymes in healthy digestion. The book addresses salient gastrointestinal features involved in healthy digestion pathophysiology, including coverage of the enzyme-microbiome connection and linkage, features of indigestion problems, roles of traditional and conventional ethnic foods, structurally diverse digestive enzymes, drugs, nutraceuticals and novel digestive formulations. In addition, the book addresses technological breakthroughs that have led to recent, novel discoveries and outlines nutritional guidelines and recommendations to achieve healthy digestion.

This book is a useful resource for nutrition researchers, nutritionists, physicians working in the field of digestive health, pharmacists, food experts, health professionals, nurses and general practitioners, public health officials and those teaching or studying related fields.

• Provides coverage of digestion, human physiology and the enzyme-microbiome linkage
• Covers indigestion problems, including gut dysbiosis and its role in chronic disease
• Addresses traditional and conventional ethic foods
• Discusses digestive enzymes, as well as digestive drugs, enzymes, nutraceuticals and novel formulations

• Language: English
• Publisher: Academic Press
• Release date: Dec 1, 2021
• ISBN: 9780128232194

Book preview

Nutrition and Functional Foods in Boosting Digestion, Metabolism and Immune Health

Editor

Debasis Bagchi

College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States

Department of R&D, Victory Nutrition Inc., Bonita Springs, FL, United States

Department of Biology, Adelphi University, Garden City, NY, United States

Sunny E. Ohia

College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States

Table of Contents

Cover image

Title page

Copyright

Dedication

Contributors

Preface

A. Introduction

Chapter 1. Chemistry and mechanism of the diseases caused by digestive disorders

Introduction

Methods

Chemistry behind human digestive system and digestive disorders

Conclusion

Chapter 2. Current trend in the pharmacotherapy of digestive disorders

Introduction

Pharmacotherapy of peptic ulcer diseases

Pharmacotherapy of gastroeosphageal reflux

Pharmacotherapy of constipation and diarrhea

Pharmacotherapy of irritable bowel syndrome

Pharmacotherapy of hemorrhoids

Pharmacotherapy of disorders of the pancreas

Pharmacotherapy of inflammatory bowel disease

Conclusions

Chapter 3. Food derived ACE inhibitory peptides: science to application

Introduction

Production of bioactive peptides

Peptide transport systems

ACE inhibitory behavior of milk fermented by Lactobacillus

Functionality of bioactive peptides

Applications of ACE inhibitory peptides for the management of health problems

Limitations and challenges

Future perspectives

Chapter 4. Age- and obesity-related metabolic changes and their impact on the incidence of digestion, metabolism, and immune health

Introduction

Impaired digestion and metabolism

Osteoporosis and its links with obesity

The obesity paradox and osteoporosis

The link between diabetes and osteoporosis

Conclusions

B. Digestion, human physiology and enzyme-microbiome linkage

Chapter 5. Digestion and immune health

Introduction

The immune system and digestive tract

Impairment of digestion

Dietary habit

Interaction of digestive and immune systems

Digestion and immune health in normal well beings and diseases

Conclusion

Chapter 6. Influence of diet on gastrointestinal immunology

Introduction

Immune cells at the gastrointestinal border

Influence of gut microbiota on immune system of gastrointestinal tract

Role of diet in immune homeostasis of the gut

Diet related dysbiosis and inflammatory diseases

Immunonutrition in the treatment of dysbiosis-related diseases

Concluding remarks

Chapter 7. Immune dysregulation in nonalcoholic steatohepatitis

Introduction to the spectrum of NAFLD

Molecular pathology of NASH

Liver damage and immune activation

Extrahepatic factors triggering inflammation in NASH

Innate immunity and NASH

Adaptive immunity and NASH

Therapeutic interventions to control inflammation in NASH

Conclusion

Chapter 8. Digestion and inflammatory responses

Introduction

Digestive system

Physiology of digestion

Pathological condition

Impact of inflammation in pathological condition

Implication of inflammation in digestion

Conclusion

Chapter 9. Digestion and gut microbiome

Introduction

Digestion

Digestive enzymes

The enzyme–microbiome linkage

Metabolic diseases related to digestive enzyme defects

How defective digestive enzymes/altered gut microbiome affects immune health

Digestive enzymes as supplements to boost immune health/gut microbiota

Conclusion

Chapter 10. Hyperlipidemia in cardiovascular health and digestion

Introduction

Lipases

Inhibition of lipase activity—control of infection and management of obesity

Chapter 11. Role of food structure in digestion and health

Introduction

Association of food structure to sensory reception

Association of food structure to digestion and health

General food digestion process

Properties of food influencing digestion process

Release of nutrients and Its bioavailability during digestion

Role of food structure in lipid digestion

Interaction of starch in food material and digestion

Behavior of protein in food matrix

Role of food structure on bioavailability of microcomponents

Modulation of food structure to improve digestion and health promoting behavior of food

Conclusion

Chapter 12. High-fat diet and constipation

Introduction

High-fat diet is a risk for functional constipation in children

High dietary saturated fat intake and constipation

HFD-induced constipation in mice

Role of mucus in the pathogenesis of constipation

Role of microbiota in HFD-induced constipation

Conclusion

Chapter 13. Effect of functional food ingredients on nutrient absorption and digestion

Introduction

Dietary fiber

Phytosterols

Polyphenolic compounds

Glucosinolates

Phytic acid

Medium-chain triglycerides

Soy proteins

C. Indigestion problems

Chapter 14. Impact of helicobacter pylori on human physiology and digestive disorders

Introduction

Epidemiology

Effect of H. pylori on human physiology

Effect of H. pylori on digestive disorders

Conclusions

D. Traditional and conventional ethnic foods

Chapter 15. Role of turmeric and cinnamon spices in digestive, metabolic, and immune systems

Introduction

Turmeric: a brief overview

Benefits of turmeric for stomach problems/digestive disorder

Effects of turmeric on the metabolism

Turmeric as immune booster

Cinnamon: an overview

Major chemical constituents

Effect of cinnamon on digestive system and metabolic disorder

Immunomodulatory effect of cinnamon

Summary

Chapter 16. Ayurvedic digestion recipes—Jal Jeera and Churan

Introduction

Healthy and refreshing Jal jeera

Jal jeera churan (dry powder) and other popular forms

Other popular digestive nutraceuticals containing Jal jeera components

Pharmacological profile of common ingredients of Jal jeera

Experimental evidences on modulation of digestion and metabolism by the common ingredients of jal jeera

Conclusion

Chapter 17. Kimchi and other fermented foods for gastrointestinal health

Introduction

Lactic acid bacteria and their functional properties in Korean fermented food

Health benefits of Kimchi, Doenjang, and Cheonggukjang

Korean fermented food for gastrointestinal health

Conclusion

Method statement

Chapter 18. Pyroglutamyl peptides in Japanese fermented foods and protein hydrolysate enhance production of host-antimicrobial peptides and ameliorate microbial imbalance

Introduction

Traditional Japanese seasonings

Generation of pyroglutamyl peptides

Effects of pyroglutamyl peptides on gut microbiota and colitis

Mechanism of effect of pyroGlu-Leu on gut microbiota

Impact of Japanese foods and protein hydrolysate on gut microbiota

Chapter 19. Jackfruit and its beneficial effects in boosting digestion and immune-enhancing properties

Introduction

Jackfruit (Artocarpus heterophyllus Lam)

Nutrition value and chemical composition

Carbohydrates

Proteins

Lipids

Secondary metabolites

Minerals and vitamins

Therapeutic values of jackfruit

Dietary fibers of jackfruit/seeds helps in digestion

Jackfruit extract inhibits hemoglobin glycation and protects internal organs

Low glycemic index by jackfruit could be due to the presence of antioxidants such as vitamin C, β-carotene, and lycopene

Immunomodulatory effect of jackfruit could be due to the presence of lectins

Jacalin

Artin M (KM+/artocarpin)

Immunomodulatory role of Jacalin and Artin M

Conclusion

Chapter 20. Combatting chronic metabolic disorders and delaying aging by improving glucose-insulin metabolism and fat accumulation in nondiabetics: emphasizing dietary links

Introduction

Historical perspective

More evidence that surplus dietary refined carbohydrates, fats, and calories cause serious metabolic perturbations

Detailing dietary constituents

IR and FM accumulation during continuum of risks period

Paradox of aging

Therapeutic interventions to maintain an optimal-working glucose–insulin system over a lifespan

E. Digestive enzymes

Chapter 21. Efficacy of N-SORB, a proprietary KD120 MEC metabolically activated enzyme formulation in digestion: a randomized, double-blind, placebo-controlled investigation and case studies

Introduction

Materials and methods

Results

Discussion

Conflict of interests and funding

F. Digestive drugs, nutraceuticals and novel formulations

Chapter 22. Fat-soluble vitamins: the key role players in immunomodulation and digestion

Introduction

An overview on immunity

Common sources and biochemical characteristics of fat-soluble vitamins

Various effects on immunomodulatory functions

Concluding remarks

Chapter 23. Health benefits of inulin-type fructan on gut microbiome, digestive health, immunity, and nutrition

Introduction

Inulin-type fructan

Fermentation of inulin-type fructan by intestinal bacteria

Nutritional function of inulin-type fructan

Summary

Chapter 24. Gut health benefits of licorice and its flavonoids as dietary supplements

Significance of licorice for gut health in traditional systems of medicine

Key chemical constituents of licorice

Use of licorice in dietary supplements

Preclinical data on gut health benefits of licorice: biological activities of licorice flavonoids

Licorice as a prebiotic for the homeostasis of gastrointestinal microbiota

Benefits of combining probiotics with licorice

Products containing licorice with probiotics in the market for gut health (Fig. 24.5)

Clinical summary of licorice containing supplements for gut health

Regulatory and safety considerations

Conclusion

Chapter 25. Prebiotics and probiotics in prevention of food allergy

Introduction

Fetal immunity responses to prebiotics and probiotics

Probiotics

Prebiotics

Food allergy

Gut microbiome and food allergy relation

Prevention of food allergy by probiotics

Role of prebiotics in preventing food allergy

Conclusion

Chapter 26. Nutraceutical and phytopharmaceuticals in immune health

Introduction

Food plants as a source for nutraceuticals

Immunomodulatory potential of phytochemicals

Digestion and bioavailability of bioactive phytochemicals derived from Curcuma longa, Moringa oleifera, and Punica granatum

Retention of immunomodulatory effects by metabolites following passage through the gastrointestinal tract

Conclusion

Chapter 27. Nutraceuticals in digestive therapy

Introduction

Lifestyle, environment, and type of diet

Human genetic variation

Summary

Summary

Conclusion

Chapter 28. Role of probiotics and prebiotics in digestion, metabolism, and immunity

Introduction

Probiotics and prebiotics in digestion

Probiotics and prebiotics in metabolism

Probiotics and prebiotics in immunity

Safety of probiotics and prebiotics

Conclusion

Chapter 29. Edible insects and gut health

Introduction

Insect components for gut health

Effect of insect components on human gut health

Effect of insect components on human health and immunity

Consumer behavior and acceptance of edible insects as food

Potential risks of entomophagy

Future prospective

Commentary: A treatise on digestive health

Index

Copyright

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Dedication

To my late, Beloved Masima Kinkori Jogeswari Devi, an Ardent Disciple of Thakur Sri Sitaramdas Omkarnath, who has been an inspirational and supportive figure in my life. With love and compassion, she always believed that with hope, perseverance, and patience anything could be achieved in this world. During December 2020, She left us for the heavenly abode. May Her Holy Soul Be Rest in Peace. Her Blessings Jai are always with us.

–Debasis Bagchi

To my Beloved Wife, Dr. Ekanam Ohia, MD

–Sunny E. Ohia

Contributors

Krishnendu Adhikary,     Department of Interdisciplinary Sciences, Centurion University of Technology and Management, R. Sitapur, Odisha, India

Amit Agarwal,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Md Akil Hossain,     Department of Pharmacology and Experimental Therapeutics, School of Medicine, Boston University, Boston, MA, United States

Mohd Fadhlizil Fasihi Mohd Aluwi,     Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Lebuhraya Tun Razak, Gambang, Pahang, Malaysia

Lin Ang

Korea Institute of Oriental Medicine, Daejeon, Korea

Korea University of Science and Techonology, Daejeon, Korea

Siddaraju Anusha

Fruit and Vegetable Technology, CSIR-Central Food Technological Research Institute, Mysuru, Karnataka, India

Academy of Scientific and Innovative Research, Ghaziabad, CSIR-Central Food Technological Research Institute, Mysuru, Karnataka, India

Jess Armine,     Nutrigenomics and Functional Medicine, The Center for Bioindividualized Medicine, Hyannis, MA, United States

Radhika Babaria,     Division of Gastroenterology, Department of Internal Medicine, University of Arizona, Tucson, AZ, United States

Debasis Bagchi

College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States

Department of R&D, Victory Nutrition Inc., Bonita Springs, FL, United States

Department of Biology, Adelphi University, Garden City, NY, United States

Manashi Bagchi,     Dr. Herbs LLC, Concord, CA, United States

Bhaskar Banerjee,     Division of Gastroenterology, Department of Internal Medicine, University of Arizona, Tucson, AZ, United States

Pradipta Banerjee

Department of Biochemistry and Plant Physiology, Centurion University of Technology and Management, R. Sitapur, Odisha, India

Department of Biochemistry and Plant Physiology, Centurion University of Technology and Management, R.Sitapur, Odisha, India

Samudra Prosad Banik,     Department of Microbiology, Maulana Azad College, Kolkata, West Bengal, India

Tejaswini Baral,     Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India

Priyadarshi Basu,     National Institute of Biomedical Genomics, Kalyani, West Bengal, India

Bharathi Bethapudi,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Jhimli Bhatttacharyya,     Department of Chemistry, National Institute of Technology Nagaland, Dimapur, Nagaland, India

Nabendu Biswas,     Department of Life Sciences, Presidency University, Kolkata, West Bengal, India

Malgorzata Bukowiecka-Matusiak,     Medical University of Lodz, Department of Structural Biology, Lodz, Poland

Izabela Burzynska-Pedziwiatr,     Medical University of Lodz, Department of Structural Biology, Lodz, Poland

Leah Bush,     Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States

Sanjoy Chakraborty,     Department of Biological Sciences, New York City College of Technology/CUNY, Brooklyn, NY, United States

Ankita Chatterjee,     National Institute of Biomedical Genomics, Kalyani, West Bengal, India

Aritra Chatterjee,     Department of Biotechnology, Paramedical College Durgapur, Durgapur, West Bengal, India

Sabyasachi Chatterjee,     Department of Chemistry and Physics, Southeastern Louisiana University, Hammond, LA, United States

Smriti Chawla,     The University of Trans-Disciplinary Health Sciences and Technology, Bangalore, Karnataka, India

Amitava Das,     Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, United States

Dolan Das,     Department of Physiology, Kalyani Mahavidyalaya, Kalyani, West Bengal, India

Sujit Das,     Department of Rural Development and Agricultural Production, North-Eastern Hill University, Tura, Meghalaya, India

S. Devaraja,     Department of Studies and Research in Biochemistry and Centre for Bioscience and Innovation, Tumkur University, Tumkur, Karnataka, India

Bernard W. Downs,     Department of R&D, Victory Nutrition Int., Bonita Springs, FL, United States

Jaclyn Downs,     Functional Genomic Fertility, Functional Genetic Nutrition, Lancaster, PA, United States

Nandini Ghosh,     Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, United States

Oksana Golovinskaia,     Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan

Osamu Handa,     Department of Internal Medicine, Division of Gastroenterology, Kawasaki Medical School, Kurashiki, Okayama, Japan

Subrota Hati,     Department of Dairy Microbiology, Anand Agricultural University, Anand, Gujarat, India

Annaelle Hip Kam

Biopharmaceutical Unit, Centre for Biomedical and Biomaterials Research, MSIRI Building, University of Mauritius, Réduit, Republic of Mauritius

Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit, Republic of Mauritius

Komal Jalan,     Department of Agriculture, University of Calcutta, Kolkata, West Bengal, India

Pradeep Reddy Kathi,     Division of Gastroenterology, Department of Internal Medicine, University of Arizona, Tucson, AZ, United States

Myung-Sunny Kim

Korea Food Research Institute, Jeonju, Jeollabuk-do, Korea

Korea University of Science and Techonology, Daejeon, Korea

Aneta Kopeć,     University of Agriculture in Krakow, Department of Human Nutrition and Dietetics, Krakow, Poland

Subrahmanya Kumar Kukkupuni,     The University of Trans-Disciplinary Health Sciences and Technology, Bangalore, Karnataka, India

Shilia Jacob Kurian,     Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India

Steve Kushner,     ALM R&D, Oldsmar, FL, United States

Hye Won Lee,     Korea Institute of Oriental Medicine, Daejeon, Korea

Myeong Soo Lee

Korea Institute of Oriental Medicine, Daejeon, Korea

Korea University of Science and Techonology, Daejeon, Korea

Himangshu Sekhar Maji,     Department of Pharmaceutical Technology, JIS University, Kolkata, West Bengal, India

Labonya Mandal,     Department of Physiology, Raja Peary Mohan College, Hooghly, West Bengal, India

A. Mavani,     Department of Chemistry, National Institute of Technology Nagaland, Dimapur, Nagaland, India

A.K.M. Moyeenul Huq,     University of Asia Pacific, Dhaka, Bangladesh

Fatima Muili,     Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States

Deepak Mundkinajeddu,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Sasi Kumar Murugan,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Sreejayan Nair,     University of Wyoming, School of Pharmacy, Laramie, WY, United States

Yuji Naito,     Department of Human Immunity and Nutrition, Kyoto Prefectural University of Medicine, Kakjiicho, Kamigyoku, Kyoto, Japan

Vidushi S. Neergheen,     Biopharmaceutical Unit, Centre for Biomedical and Biomaterials Research, MSIRI Building, University of Mauritius, Réduit, Republic of Mauritius

Pradeep Singh Negi

Fruit and Vegetable Technology, CSIR-Central Food Technological Research Institute, Mysuru, Karnataka, India

Academy of Scientific and Innovative Research, Ghaziabad, CSIR-Central Food Technological Research Institute, Mysuru, Karnataka, India

Kalu Ngele,     Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States

Muruganantham Nithyanantham,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Ya Fatou Njie-Mbye,     Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States

Sunny E. Ohia,     Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States

Anthonia Okolie,     Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States

Catherine A. Opere,     Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, NE, United States

Harry G. Preuss,     Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC, United States

Mahadev Rao,     Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India

Moumita Ray,     Department of Pharmaceutical Technology, JIS University, Kolkata, West Bengal, India

Akanksha Rout,     Department of Zoology, Centurion University of Technology and Management, R.Sitapur, Odisha, India

Marufa Rumman,     Department of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, Redfield, AR, United States

Hephzibah Saji,     National Institute of Food Technology Entrepreneurship and Management (NIFTEM), Sonipat, Haryana, India

Saptadip Samanta,     Department of Physiology, Midnapore College, Midnapore, WB, India

Riya Sarkar,     Department of Biotechnology, Paramedical College Durgapur, Durgapur, West Bengal, India

Kenji Sato

Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan

Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan

Shalini Sehgal,     Department of Food Technology, Bhaskaracharya College of Applied Sciences, University of Delhi, Dwarka, New Delhi, India

Sonal Sekhar M,     Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India

M.N. Sharath kumar,     Department of Studies and Research in Biochemistry and Centre for Bioscience and Innovation, Tumkur University, Tumkur, Karnataka, India

Saki Shirako,     Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan

Abhilasha Singh,     Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States

Vineet Kumar Singh,     Research and Development Center, Natural Remedies Private Limited, Bengaluru, Karnataka, India

Derek Smith,     University of Wyoming, Department of Kinesiology and Health, Laramie, WY, United States

Eunhye Song,     Korea Institute of Oriental Medicine, Daejeon, Korea

G. Sowmyashree,     Department of Biochemistry, Mount Carmel College Autonomous, Bengaluru, Karnataka, India

Tomohisa Takagi,     Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kamigyoku, Kyoto, Japan

Md Hafiz Uddin,     Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States

Chethala N. Vishnuprasad,     The University of Trans-Disciplinary Health Sciences and Technology, Bangalore, Karnataka, India

Sayori Wada,     Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto, Japan

Chin-Kun Wang,     Department of Nutrition, Chung Shan Medical University, Taichung, Taiwan

Lucyna A. Wozniak,     Medical University of Lodz, Department of Structural Biology, Lodz, Poland

Orie Yoshinari,     Faculty of Economics, Keio University, Tokyo, Japan

Jerzy Zawistowski,     University of British Columbia, Faculty of Land and Food Systems, Vancouver, BC, Canada

Preface

The process of digestion of foods that we consume as humans is an important step of metabolism in our survival on earth. In fact, digestion is a vital action in which ingested food is broken down physically and mechanically by the grinding action of teeth in the oral cavity, followed by movement of the bolus from the mouth via the esophagus to other parts of the gastrointestinal tract where a sequence of events including propulsion, absorption, physical/chemical/enzymatic digestion, and defecation occurs. Digestive enzymes play an important role in transforming the ingested food into a form suitable for absorption, digestion, metabolism, and assimilation of nutrients into the body to sustain our overall well-being as humans. It is pertinent to note that the two most important factors of a healthy life are (1) Healthy Nutrition and (2) Healthy Digestion. If these two factors can be managed properly, there will be great positive influence in our state of health in the current and future population of the United States and the world at large.

Interestingly, human gastrointestinal tract is equipped with more than 100 million cells of the enteric nervous system leading to its description as a brain unto itself. The enteric nervous system utilizes more than 30 neurotransmitters, most of which are identical to the ones observed in the central nervous system, such as dopamine, serotonin and acetylcholine, and almost 95% of body's serotonin is found in the gastrointestinal tract. The gastrointestinal tract always communicates to the brain, releasing signaling molecules/hormones into the bloodstream which indicates how hungry a person is or their ability to experiencing craving for a particular food such as sugar.

A wide variety of nutritional resources such as vitamins, antioxidants, micronutrients, macronutrients, amino acids, fatty acids, and structurally diverse phytochemicals play significant roles in building the healthy infrastructure and integral function of the vital cells in the body. Numerous metabolic functions and organs are involved in the digestive process. The digestive system plays an important role in serving as a mini brain, enhancing immune competence and contributing to overall metabolic homeostasis. Taken together, every organ/tissue in the body is influenced by the health and function of the digestive system. Consequently, there is a growing need for a comprehensive appraisal of the value of nutritional benefits in healthy digestion, a major focus of the present book as addressed in this volume entitled "Digestion, Metabolism, and Immune Health."

The present book addresses a wide range of topics related to the role of appropriate nutrition and digestive enzymes in healthy digestion written by leading experts in the field. To provide a comprehensive approach to the emerging fields of nutrition, digestive enzymes and healthy digestion, immune competence, and metabolism, this book covers numerous chapters describing the salient gastrointestinal features involved in healthy digestion pathophysiology. Topics covered include enzyme-microbiome connection and linkage, features of indigestion problems, roles of traditional and conventional ethnic foods, nutraceuticals, drugs, and novel structurally diverse digestive enzyme–based formulations. Leading researchers have addressed the technological breakthrough involved in the novel discoveries unveiled in the past few years. Furthermore, the present book addresses nutritional guidelines and recommendations necessary to promote healthy digestion.

The current book is divided into six main themes consisting of 29 independent chapters. The introductory theme is comprised of four chapters. The first chapter demonstrates the chemistry and mechanism of the diseases caused by digestive disorders, while the second chapter highlights the current trend of pharmacotherapy of digestive disorders. The third chapter elaborates the intricate aspects of food derived angiotensin converting enzyme (ACE) inhibitory peptides, while the fourth chapter discusses the influence of advancing age- and obesity-related metabolic changes and their impact on the incidence of digestion, metabolism, and immune health.

The second section presents aspects of digestion, human physiology, and the salient features of enzyme–microbiome linkage in nine independent chapters. The first chapter highlights the importance of digestion in boosting/modulating immune health, followed by a chapter that highlights the influence of diet on gastrointestinal immunology, with the third chapter elaborating detailed aspects of immune dysregulation in nonalcoholic steatohepatitis (NASH). The fourth chapter of this section discusses aspects of digestion that influences inflammatory responses, while the fifth chapter elaborates the roles of a healthy gut microbiome on digestion and immune health. The sixth chapter elaborates the influence of hyperlipidemia in cardiovascular health and digestion, followed by a chapter that discusses the roles of food structure on the aspects of digestion and human health. The eighth chapter demonstrates the effect of high-fat diet on digestive health and constipation. The last chapter of this section elaborates the effects of functional food ingredients on nutrient absorption and digestion.

The third section is focused on indigestion problems and begins with a chapter that highlights the impact of noxious bacteria Helicobacter pylori on human health and a vast array of digestive disorders.

The fourth section is focused on how diverse traditional and conventional ethnic foods expose the reader to the importance of different types of foods on a health digestive process. In the first chapter, the roles of Indian spices such as turmeric and cinnamon in boosting digestive, metabolic, and immune competence are discussed, followed by a chapter that demonstrates the beneficial aspects of Ayurvedic digestion recipes on digestion. The next chapter discusses the valuable digestive benefits of Korean fermented foods including Kimchi. The fourth chapter highlights the digestive benefits of pyroglutamyl peptides in Japanese fermented foods and how protein hydrolysates enhance the production of host-antimicrobial peptides in ameliorating microbial imbalance. The next chapter discusses the benefits of Jackfruit in boosting digestive health and immune competence. The last chapter in this section extensively discusses how healthy nutrition can improve glucose–insulin metabolism in combatting chronic metabolic disorders and fat accumulation in nondiabetics.

The fifth section is focused on the role of digestive enzymes and elaborates clinical findings of digestive benefits of a proprietary enzyme formulation in human volunteers with an emphasis on the correlation of digestion, quality of sleep, and their effects on neurotransmitters and affected neuronal functions.

The sixth section is comprised of eight independent chapters which address the role of selected digestive drugs, nutraceuticals, and novel formulations as agents to boost digestive health. The first chapter elaborates the roles of fat-soluble vitamins in boosting immune competence and digestive health, while the second chapter demonstrates the beneficial benefits of inulin-type fructan on gut microbiome, digestion, and immune competence. The third chapter discusses the digestive benefits of licorice and its bioflavonoid constituents. The fourth and fifth chapters demonstrate the beneficial roles of prebiotics and probiotics in the prevention of food allergy as well as in boosting digestive health, metabolic homeostasis, and immune competence. The sixth and seventh chapters demonstrate the roles of structurally diverse nutraceuticals and phytopharmaceuticals in boosting digestive health and immune competence. The eight and last chapter elaborate the roles of edible insects in boosting gut health.

The Editors crafted a Commentary entitled "A Treatise on Digestive Health" and summarizes a vivid scenario of diverse aspects involved therein.

Our sincere gratitude and thanks to all our eminent contributors, as well as helpful Elsevier/Academic Press editorial team members including Megan R Ball, Lindsay Lawrence, and Swapna Praveen for their continued support, cooperation, and assistance.

Debasis Bagchi, Ph.D., MACN, CNS, CFFS, MAIChE

College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States;

Department of R&D, Victory Nutrition Inc., Bonita Springs, FL, United States; Department of Biology, Adelphi University, Garden City, NY, United States.

Sunny E. Ohia, PhD, FARVO, FAS

College of Pharmacy and Health Sciences,Texas Southern University, Houston, TX, United States.

A

Introduction

Outline

Chapter 1. Chemistry and mechanism of the diseases caused by digestive disorders

Chapter 2. Current trend in the pharmacotherapy of digestive disorders

Chapter 3. Food derived ACE inhibitory peptides: science to application

Chapter 4. Age- and obesity-related metabolic changes and their impact on the incidence of digestion, metabolism, and immune health

Chapter 1: Chemistry and mechanism of the diseases caused by digestive disorders

Sabyasachi Chatterjee ¹ , A. Mavani ² , and Jhimli Bhatttacharyya ²       ¹ Department of Chemistry and Physics, Southeastern Louisiana University, Hammond, LA, United States      ² Department of Chemistry, National Institute of Technology Nagaland, Dimapur, Nagaland, India

Abstract

Food traveling from our mouth to digestive systems gets broken by various digestive enzymes. Thus smaller nutrients are formed which can easily be absorbed by our bodies. This method is termed as chemical digestion. Both mechanical digestion and chemical digestion are responsible for proper intake and nourishment of body through foods. However, if the process of chemical digestion is interrupted, our body will face vitamin deficiencies, malnutrition, and various diseases. Sometimes, lack of certain enzymes hinders the process of chemical digestion of food. For example, lactose intolerance is a very common but serious gastrointestinal disorder found in adults. Here, the people cannot digest lactose, a natural sugar present in milk, yogurt etc., dairy products leading to severe symptoms like abdominal stomach pain, bloating, diarrhea, gastric, and nausea. In this chapter, we have discussed the chemical reason and mechanism (wherever possible) of some digestive disorders like celiac disease, Crohn's disease, Gaucher disease, gastric ulcer, lactose intolerance, etc.

Keywords

Chemical and mechanical digestions; Digestive disorders; Enzymes; Food and nutrition; Gastro-intestinal diseases

Introduction

The food is the major source of energy which is required to run our body parts. Proper intake food can be compared with fueling a tank to keep it running. Usually, food supplies many types of macro and micronutrients like carbohydrates, fats, proteins, vitamins, minerals, etc., which deliver the energy (generally measured in calories/kilo calories) and required supports, our body needs to function. Though the micronutrients (vitamins and minerals) do not produce energy directly, without them, our bodies will face severe difficulties in proper functioning. However, only food intake is not enough for a body to function. Proper digestion is the key ailment through which the complex food is converted in simpler forms which can be absorbed by our bodies.

There are two types of digestions, chemical and mechanical, which complete the whole task. Mechanical digestion is all about the physical movements which cuts the food into smaller pieces, whereas chemical digestion uses enzymes (catalyst for a specific biochemical reaction) for breaking down the food into smaller parts. These fragmented versions are usually simple and ready for easy absorption. Peristalsis is an important fragment of mechanical digestion which offers involuntary contractions and relaxations of the muscles of the esophagus, stomach, and intestines to disintegrate food and deliver it through the digestive system. Chewing in mouth followed by churning in stomach and then segmentation in the small intestine, all are included in mechanical digestion. After entering the small intestine, the food particles continue moving through the mechanical digestion and become exposed toward the digestive enzymes more and more. With the help of such movements, digested along with the undigested part of food reaches the large intestine for eventual excretion. Thus, mechanical and chemical digestion work together to complete the cycle of energy production and body parts maintenances from foods.

Again, almost all of us suffer from few digestive disorders like gastritis, bloating, or heartburn in our lifespan. In many cases, problems are not very severe, but few cases become very serious, and in worst case, the patient may die even. Few patients have permanent, nagging problems which hinder from living a healthy life. Our alimentary canal (i.e., the digestive system) (Fig. 1.1) includes the gastrointestinal tract (GI), liver, pancreas, and gallbladder which help in food digestion inside human body. The GI tract is usually affected due to digestive problems and may cause stomach pain, bloating, heartburn, stomach upset or loose motion (diarrhea), nausea and emesis (vomiting), etc. In some cases, constipation and bleeding can also be experienced. However, to treat any digestive disorder, the background or scientific reason of the problem is to be known clearly. More precisely, the chemistry and mechanism behind the disease should be carefully understood so that the disorder can be cured through its root cause analyses and accurate medication. The major parts of our digestive systems are chemicals which are present in the stomach. They are pepsin, gastric juice, and hydrochloric acid (HCl). Various enzymes, which act as catalysts to the biochemical reactions inside human body, are also nothing but complex molecules. Thus, a thorough knowledge of the chemistry behind the digestive processes and any disorders can very useful. The major and common diseases which are caused by digestive disorders are gastro-esophageal reflux disease (GERD), diarrhea, chronic constipation, gastroenteritis, ulcers, hemorrhoids, etc. The current protocols cover such root causes and symptoms of few common gastro-intestinal/digestive disorders in brief.

Figure 1.1 Human digestive system. 

Source: Internet.

Methods

We sought to review the various reported data on digestive disorder disease information in the literature. Only the publications relevant to the title were considered.

Chemistry behind human digestive system and digestive disorders

As already mentioned, food perform an enormous role in the living system. And digestion is the process of breaking down the food into micronutrients, which are small and simple enough to be absorbed by cells.

The digestion process started from chewing (mechanical digestion) in our mouth; but chewing is not enough to breakdown food to its micronutrient. That is why we need chemical digestion. Chemical digestion involves the secretions of different enzymes throughout digestive tract. Chemical digestion breaks down different nutrients, such as proteins, carbohydrates, and fats, into their building blocks: fats disintegrate into fatty acids and monoglycerides; nucleic acids turn into nucleotides (adenine, cytosine, guanine, thymine, and uracil); polysaccharides, or carbohydrate sugars, break down into monosaccharide and proteins break down into amino acids.

In human body, the chemical digestion starts in the mouth. The salivary glands (located underneath the tongue) secrete saliva which mixes with foods while chewing inside the mouth. Saliva contains enzymes (like amylase) and breaks/digests the carbohydrates. The saliva contains mucus and hydrogen carbonate. Mucus lubricates the food to help moved toward stomach and hydrogen carbonate helps the ideal alkaline pH environment for amylase to work. Amylases hydrolyze starch and other carbohydrate polymers into simple sugars form. The presence of amylase in the saliva is called salivary amylase (Fig. 1.2A), and it helps the carbohydrate digestion. Amylases generated in the pancreas are termed as pancreatic amylase (Fig. 1.2B). In humans, both the salivary and pancreatic amylases are α-amylases. Salivary amylase acts on the raw form of carbohydrates inside the mouth. And, pancreatic amylases work on complex carbohydrates and complete the hydrolysis of carbohydrates.

Then the semidigested food enters into the stomach through pharynx (tubular entrance) and esophagus (food tube). Inside the stomach, food mixed with gastric fluid contains HCl, pepsin, and other fluids. Chymosin or rennins are found to be present in the gastric juice of infants and toddlers. Chymosin is found to be associated primarily with the digestion of milk. After consumption of milk, HCl initiates the inert prorenin and signals it to produce the active rennin. As one grows old, the production of chymosin in the human body begins to subside and then is replaced by pepsin and trypsin (Fig. 1.3), which is another digestive enzyme produced by the stomach. The gastric fluid is extremely acidic (due to presence of HCl) and it helps kill pathogens enter with the food. Digestion of protein started from the stomach. The acidity of the stomach denatures the proteins and unfolding their three-dimensional structure to reveal just the polypeptide chain. Chemical digestion of proteins is initiated by the denaturation or unfolding process. After denaturation, protein loses its regular function and becomes polypeptide chain. This is the reason, protein such as insulin (control blood glucose level) cannot be taken as an oral medication. Its function is destroyed by HCl and enzymatic digestion. Instead, it has to be injected so that it is absorbed intact into the bloodstream. After remaining in the stomach for a couple of hours (approximately 3–4   h), the food enters the small intestine. The duodenum, jejunum, and ileum are the major components of the small intestine. The internal layers of the intestine are wrapped with tiny finger-like projections called villi. Villi are even covered with further smaller parts which are known as microvilli. These microvilli are responsible for absorbing various nutrients from foods (which have already undergone chemical digestion). Proteins, carbohydrates, fats, vitamins, minerals, etc., are the major nutrients which our body needs for nutrition and most of them made available in this stage. The nutrition-free left over (contains water, cellulose, and indigestible materials) stuff then moves to large intestine. After this process, the nutrients are absorbed into the bloodstream and transported to the liver for further processing. Then, to the large intestine the undigested material is transferred for bacterial fermentation. Without chemical digestion, body would not be able to absorb nutrients, leading to vitamin deficiencies and malnutrition. Some people may lack certain enzymes used in chemical digestion. Here, we described 10 such diseases which directly hampered our regular digestive system.

Figure 1.2 Protein data bank (PDB) structures of human salivary amylase (PDB ID 1SMD) (A) and human pancreatic amylase (1HNY) (B).

Figure 1.3 Conversion of protein to peptide by (A) pepsin and (B) trypsin.

Celiac disease

Celiac disease is an extremely serious digestive disorder which damages the small intestine very badly (Fig. 1.4). It can thus hamper the immunity as well. It belongs to autoimmune category. It can be initiated or triggered by gluten-rich food intake. Glutens are a class of protein which can be located in grains: wheat, rye, barley, etc. Gluten proteins develop a sticky nature that has a glue-like behavior, when mixed with water. Hydrated gluten proteins are of two categories—gliadins (soluble) and glutenins (insoluble). With little elasticity and less cohesive nature, the hydrated gliadins (compared to glutenins) can influence the viscosity and extensibility of the dough system to a major part (Definition & Facts for Celiac Disease; Caio et al., 2019; Leonard et al., 2017; Parzanese et al., 2017; Sollid, 2000). A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is responsible for this disease to happen, both as a dimidiating enzyme that can enhance the immune stimulatory effect of gluten and as a target autoantigen in the immune response (Martina et al. 2018). Presence of this gene can cause celiac disease in some patients but it's not obvious for everyone. For some people, the gene may not be predominant. Dr. Samuel Gee reported about Celiac disease for the first time in 1887. Diarrhea/loose motion, stomach pain, nausea, vomiting, etc., are the usual symptoms of this disease. Gluten intolerance can also cause severe weight loss, continuous tiredness (fatigue), bloating, constipation, itchy and blistering skin rashes, etc., for some patients. However, it is also observed that celiac disease can cause bone-related diseases (osteoporosis, osteomalacia), anemia, headaches and fatigue, joint pain, hyposplenism, etc., that does not seem to be celiac symptoms.

Figure 1.4 Difference between healthy villi and villi affected by celiac disease. 

Source: internet.

Nonceliac gluten sensitivity

Some people have reaction to glutens and reported unpleasant digestive symptoms though they do not suffer from celiac disease. This reaction of gluten is known as non-celiac gluten sensitivity. In this kind of sickness, associating with glutens causes irritation and inflammation of the digestive system, which commonly leads to stomach disorder and discomfort such as diarrhea, constipation, bloating, etc (Roszkowska et al., 2019; Barbaro et al., 2018).

Crohn's disease

Crohn's disease is a family of inflammatory bowel disease (IBD). It is one of the most common sicknesses known under IBD. It is considered to be a chronic disease, which causes inflammation in digestive tract. Some common symptoms which are caused by Crohn's disease are stomach pain, cramps, diarrhea, abdominal pain, tiredness, body disorder, and malnutrition. In Crohn's disease, any part of small or large intestine can be involved. The disease can spread continuously or may involve multiple segments (Fig. 1.5). In few cases, the disease remains in the large intestine (which is known as colon). The cause and cure are still unknown. Most of the people suffer in between 20s and 30s of their age. Crohn's disease can cause many complications to a person suffering from this disease. But with proper treatment and medication, the symptoms can be subsided and cured (Ho and Khalil, 2015; Baumgart and Sandborn, 2012; Franklin, 2018). An autoimmune reaction is one of the possible ways which a researcher suggests. This reaction is prevalent when a healthy cell of the body is attacked by our own immune system causing chronic inflammation. Since this Crohn's disease passes down in families, it is expected to be involved genetically. According to Crohn's and Colitis Foundation, there are five types of Crohn's disease. All the five types cause various complications and symptoms to the digestive tract. These are ileocolitis, ileitis, gastro-duodenal Crohn's disease, jejunoileitis, and Crohn's colitis.

Figure 1.5 Changes of small intestine due to Crohn's disease.

Gaucher disease

Gaucher disease is developed from mutations at the glucocerebrosidase locus on chromosome 1q21. It is a genetically inherited metabolic disorder. In this disease, glucosylceramide (glucocerebroside) is stored in the reticulo endothelial system due to a deficiency of the lysosomal enzyme β-glucocerebrosidase (Nagral, 2014; Stirnemann et al., 2017). Deficiency of the enzyme glucocerebrosidase gives rise to fat-laden Gaucher cells build up in areas like the spleen, liver, and bone marrow, which causes these organs to enlarge and unbalance their function. It can also weaken the bone by developing fatty substances in bone tissue. If the bone marrow is affected, it can directly interfere with blood coagulation cascade. Gaucher disease is most common in Jewish people of Eastern and Central European descent (Ashkenazi). Symptoms can appear at any age of life. Unusually enlarged liver, spleen (hepatosplenomegaly), skeletal abnormalities, and low levels of circulating red blood cells (anemia) and platelets (thrombocytopenia) are some of the prevalent symptoms observed from the patient suffering from Gaucher disease. Some patients suffering from Gaucher disease do not show any symptoms, while others may develop severe complications. It's directly affected blood coagulation cascade. A person will suffer with this disease if both parents are carriers of the disease, which gives a chance of one in four in each pregnancy that the baby will be born with the disease. Three major types of Gaucher disease are identified and separated. Type 1 is the absence of neurological complications which is the most prevalent type among the three; Type 2 and 3 are presence and extent of neurological complications, which are known as neuronopathic forms of the disorder. They can also be identified through abnormal problems that affect the central nervous system (Grabowski, 1882; J. Stirnemann et al., 2017; Bennett and Mohan, 2013).

Ulcer

Presence of acid peptic juices in the lining of the stomach can cause painful ulcers, which is known as peptic ulcer disease. Presence of thick layer of mucus in the stomach protects the lining from the effect of its digestive juices. Rise in acidity can damage the protective layer and harm the tissue. Traditionally, it was believed that the hypersecretory acidic environment is fully responsible with dietary factors or stress. With the advancement in the medical field, and the finding of Helicobacter pylori (H. pylori), disease and the extensive use of nonsteroidal antiinflammatory drugs have altered this idea. With the discovery of H. pylori in 1982, new ideas are dawn into the cause and sickness of ulcer. Mental and physical stress, food habit, and lifestyles are found to be the causing agent of peptic ulcer (Kuna et al., 2019; Narayanan et al., 2018; Majumdar et al., 2011). As per the famous pathologist, Dr. Robin Warren (from Australia), almost half of biopsy reports indicate the presence of colonies of a very specific/typical bacteria in the antrum. He had reported the same after taking samples from patients suffering from peptic ulcer. Followed by Dr. Warren's observation, Dr. Barry Marshall studied similar diseases and patients thoroughly. Both the scientists together had carried out huge number of biopsies of the peptic ulcer samples. A spiral-shaped, gram-negative bacterium was found in the culture media originated from patient biopsy samples. This new bacterium is nothing but H. pylori. This discovery led to Nobel Prizes in Physiology/Medicine (2005) for both the scientists jointly. The various proteins secreted by H pylori strains can be correlated with the potency of virulence and to the host immune response. The produced urease makes the surrounding alkaline which is mandatory for the bacteria to survive in the mucosal barrier of the stomach. Expression of adhesins like blood group antigen adhesin (BabA) and outer inflammatory protein adhesin (OipA) facilitates the binding between the bacteria and gastric epithelium. The acid as well as the bacteria disturbed the lining which leads to a kind of ulcer and a sore. During the attachment of H. pylori bacteria to the protective mucous coating of the duodenum and the stomach, it weakens them and allows the acid to get into the sensitive lining (Kavitt et al., 2019; Soll, 1996).

Lactose intolerance

Generally, most of the mammals can digest lactose which is present in the milk. Thus, a newly born infant gains adequate energy from the milk on which he/she survives. Lactose is a disaccharide which is digested by lactase enzyme and breaks down into glucose and galactose in the small intestine (Fig. 1.6). The resultant monosaccharides (glucose and galactose) can be absorbed through the small intestine and thus enter into the bloodstream. Lactose intolerance is faced by those persons consuming dairy products. The excess of consumed lactose (which was not digested in the small intestine) gets fermented by the bacteria present in the large intestine. This produces a significant amount of carbon dioxide gas and can cause discomfort sometimes (Szilagyi and Ishayek, 2018; Deng et al., 2015). In most of the cases, lactase expression reduces between the ages 2 and 12. The cells that are responsible for generating the lactase lose their efficiency to generate the required amount of enzyme as people get matured. The problem of lactose intolerant begins when the lactase gene does not express efficiently though they are present in the body. With the damage of lactase-producing cells in the intestines, other signs of lactose intolerant are develop. Like celiac disease has an immune reaction against gluten, this immune reaction damages the intestinal lining over time which disturbed lactase production (Misselwitz et al., 2019; El Guindi and Nazer, 2012).

Valinemia

The increased level of valine, an essential amino acid, in the blood and urine is indicative of the disease valinemia. It is a rare metabolic disorder and considered to be a congenital defect of metabolism. Regular vomiting, protein intolerance, metabolic acidosis, feeding difficulties, hypotonia (very low muscle toning), developmental disorder, appetite loss, etc., are the typical symptoms of valinemia. This is mainly caused due to the deficiency of the enzyme, valine transaminase, which is required for the breakdown (metabolism) of valine. This disease has been reported for newborns. In some cases, hyperactivity, hyperkinesia, severe drowsiness, delayed mental and physical developments, etc., can also be seen (Valinemia; Valinemia).

Figure 1.6 Chemical breakdown of lactose to galactose and glucose by enzyme lactase.

Propionic acidemia

Propionic acidemia is a digestive disorder caused due to the deficiency of the enzyme, propionyl-CoA carboxylase. This enzyme deficiency is basically the result of the mutation in the PCCA and PCCB genes. The essential amino acids, which are responsible for growth and development, are valine, threonine, isoleucine, and methionine. Propionyl-CoA carboxylase catalyzes the breakdown of the above mentioned amino acids. It also catalyzes few fatty acids, cholesterol, etc., which are required in the process of metabolism. Thus, deficiency in propionyl-CoA carboxylase can lead to accumulation of harmful chemicals components (toxic metabolites) in body, followed by malfunction of the cellular power house, mitochondria (Grünert et al., 2013; Wolf et al., 1981). Propionic acidemia is also a congenital disease and occurs almost immediately after birth. Poor feeding nature, puking, hypotonia, fatigue, etc., are the common symptoms of the said disease. This usually occurs within the first few days after birth. If not diagnosed or treated in at the early stage, the apparently common symptoms can lead to very serious health hazards. Medical problems like heart disorders, convulsion, intellectual disability/down syndrome, coma, and even death can also happen from propionic acidemia.

Maple syrup urine disease

Maple syrup urine disease (MSUD), the autosomal recessive disorder, is characterized by malfunctioning of α-keto acid dehydrogenase in the human body. This digestive disorder increases the level of the branched chain amino acids in blood plasma and α-keto-acids in urine. The pathognomonic disease marker, alloisoleucine, is produced during the process. As a result, a unique sweet odor is observed in the infant's urine samples and thus this sickness is named as MSUD. Mutations in the DBT, BCKDHA, and, BCKDHB kind of genes reduce the function of protein complex and that in turn leads to maple syrup urine disease MSUD. These three genes play the pivotal role for producing the protein cluster which can function together as the major part of an important complex. Protein complexation is essential for digestion of the common amino acids like isoleucine, leucine, valine, etc. These amino acids are found in the common proteins and essential for both physical and mental growth. Increased quantity of the said components can be toxic to the brain and other vital organs of our biological systems. Their accumulation can lead to very serious medical problems as a result of MSUD (Blackburn et al., 2017; Dancis et al., 1959; Lane, 1961). The major amino acid toxicity occurs due to leucine. In some cases, additional quantity of valine and isoleucine is given during the course of treatment. Metabolic acidosis is the resultant of unwanted accumulation/storage of the respective ketoacids in the biological systems.

Irritable bowel syndrome

Irritable bowel syndrome (IBS) is a series of intestinal symptoms that arise together, with nagging stomach pain, cramps, bloating, and finally compromised bowel movements. This is one of the most common diseases found on this earth. Diarrhea, or constipation, or both, is also typical symptom of IBS. These symptoms or signs vary from person to person. Unhealthy diet, stress, anxiety, sleeping disorder, irregular life style, etc., can trigger the disease (Seyedian et al., 2019; Drossman et al., 2009; Camilleri et al., 2016; Javier et al., 2021). Though IBS is not life threatening, it's a long-lasting and nagging problem which decreases the quality of lives.

Four different IBS types are as follows:

1. IBS with constipation (IBS–C)

2. IBS with diarrhea (IBS-D)

3. Mixed IBS (IBS-M) alternates between constipation and diarrhea

4. Unsubtyped IBS (IBS–U) for people who do not fit into the above types

Recently, research studies revealed that several chemical and molecular factors play important roles in case of IBS. Usually IBS with diarrhea is the most common one. Variations in bile acids, short-chain fatty acids, mucosal barrier proteins, mast cell products such as histamine, proteases, and tryptase; enteroendocrine cell products; mucosal mRNAs, proteins, and microRNAs are actively involved for IBS. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) (Fig. 1.7) are also directly connected with IBS (Barrett and Gibson, 2012). Generally, these molecules cannot be digested or absorbed by the small intestine. After consumption of enough FODMAPs, the compounds pass through the small bowel mostly untouched into the colon, where bacteria ferment them into gases. Hydrogen (H2), carbon dioxide (CO2), and methane (CH4) are the common byproducts for this process. The short-chain fatty acids bring water into the bowel via osmosis, making stool watery and causing diarrhea.

Barrett's esophagus

Barrett's esophagus is a typical medical condition where intestine tissue lining replaces the esophagus tissue lining. This kind of sickness can develop a cancer called esophageal adenocarcinoma. Mortality rate is quite high for this disease and it's rapidly increasing all over the world. Acid reflux or GERD is related to Barrett's esophagus. Sometimes, patients with chronic symptoms of GERD are found to develop this disease. Barrett's esophagus can be detected by endoscopic techniques. It can also be pathologically confirmed by the presence of intestinal metaplasia on biopsy (Suzuki et al., 2005).

Figure 1.7 Examples of FODMAP molecules.

Conclusion

In this chapter, the background of various digestive disorders has been discussed and explained briefly. Special attention has been given toward the chemical reasoning and mechanism of the gastrointestinal diseases. Chemistry is omnipresent in daily life starting from the tasty and healthy foods, the air we breathe, medicines, cleaning agents, cosmetics, etc., to the chemicals which control our emotions. The human body itself is made up of chemical compounds, which are combinations of different elements. The digestion is the key factor through which body gets its required fuel for running all its machineries. Ingestion, propulsion, mechanical or physical digestion, chemical digestion, absorption, and defecation are the major activities which related intake to final fate of foods in the Any disorder in digestion causes severe symptoms in us like gas, bloating, constipation, diarrhea, heartburn, etc. Other signs can be unintentional weight changes sleeping disturbances, fatigue, skin rash, and food intolerances. In all the cases, certain chemicals are responsible for either good or bad. Their structures, working principle, mechanism of action, and last but not the least, their importance have been discussed in this chapter.

Acknowledgment

JB acknowledges the financial assistances from UGC-DAE, Mumbai Centre, BARC, Mumbai (grant no. CRS-M-266); DBT Govt. of India (sanction no. BT/PR25026/NER/95/963/2017); and TEQIP-III Seed Grant, NIT Nagaland.

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Chapter 2: Current trend in the pharmacotherapy of digestive disorders

Sunny E. Ohia ¹ , Ya Fatou Njie-Mbye ¹ , Catherine A. Opere ² , Kalu Ngele ¹ , Fatima Muili ¹ , Anthonia Okolie ¹ , and Leah Bush ¹       ¹ Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, United States      ² Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, NE, United States

Abstract

Diseases of the gastrointestinal tract (also known as Digestive Disorders) afflict 40% of the world's population with more females suffering from this illness. Common examples of these diseases include peptic ulcer, gastroesophageal reflux, constipation, diarrhea, hemorrhoids, irritable bowel disease, hemorrhoids, inflammatory bowel disease, and diseases of the accessory organs of the digestive system such as pancreatitis and diabetes mellitus. Both nonpharmacological and pharmacological approaches are used for treatment of digestive disorders. Nonpharmacological treatment of digestive disorders includes lifestyle changes and diet control which, in combination, can alleviate the impact of these diseases on the population. Pharmacological therapy of digestive disorders includes a wide variety of drugs that affect motility, enzymatic and chemical processes, inflammation, and the immune system. Both providers of health care and their patients should consider all approaches in the treatment of digestive disorders.

Keywords

Constipation; Diabetes mellitus; Diarrhea; Gastroesophageal reflux; Hemorrhoids; Inflammatory bowel disease; Irritable bowel syndrome; Pancreatitis; Peptic ulcers; Pharmacotherapy

Introduction

Digestive disorders is a collective term that encompasses a broad spectrum of gastrointestinal diseases, including peptic ulcers; gastroesophageal reflux disease (GERD); constipation; diarrhea; irritable bowel syndrome (IBS); pancreatic disorders; hemorrhoids; and inflammatory bowel disease (IBD). Digestive disorders affect 40% of the population worldwide, with a higher prevalence reported in females than males (Sperber et al., 2020). In the United States, digestive disorders account for over 100 million ambulatory care visits annually (Amario et al., 2018) and are approximated to be responsible for 25% of all surgical procedures. To date, digestive disorders are the most prevalent causes of disability in the labor force, with an estimated direct cost of $136 billion annually to the US economy (Peery et al., 2018). Peptic ulcer disease, which consists of gastric and duodenal ulcers, is one of the most prevalent gastric disorders. Over the past few decades, the incidence of peptic ulcer disease has declined due to the introduction of proton pump inhibitors (PPIs) and the discovery of the etiological role of Helicobacter pylori (H. pylori) in the pathogenesis of the disease (Malfertheiner et al., 2009). The lifetime prevalence of peptic ulcer disease is estimated to be equivalent in males and females (about 11%–14% in men and 8%–11% in women) (https://www.medscape.com/answers/181753-13866/what-is-the-prevalence-of-peptic-ulcer-disease-pud-in-the-us). In the United States, peptic ulcer disease was reported to affect 15.5 million in the year 2011, accounted for 669,000 ambulatory care visits between 2006 and 07 and 358,000 hospitalizations in 2010 (https://www.niddk.nih.gov/health-information/health-statistics/digestive-diseases). GERD is also one of the most prevalent gastrointestinal diseases in the United States, affecting approximately 20% of the population. In the United States, GERD was reported to account for 8.9 million ambulatory care visits in 2009 and 4.7 million hospitalizations in 2010 (https://www.niddk.nih.gov/health-information/health-statistics/digestive-diseases). Both peptic ulcer disease and GERD present a significant negative impact on the quality of life and exert a heavy burden in direct and indirect costs to the US economy (El-Serag et al., 2014; Fass and Frazier, 2017; Barkun et al., 2010). Constipation is estimated to affect up to 20% of the population, with the incidence of chronic constipation reportedly higher in the elderly than in younger individuals and more common in females, compared to their male counterparts (Vazquez Rogue and Bouras, 2015). In the United States, chronic constipation was reported to affect 63 million people in 2000, accounted for 4 million ambulatory visits in 2009 and 1.1 million hospitalizations in 2010 (https://www.niddk.nih.gov/health-information/health-statistics/digestive-diseases). Diarrhea is another digestive disorder that has a significant impact, worldwide, especially in children. Chronic diarrhea is reported to affect 1%–5% of general population (Schiller et al., 2017). Although death caused by diarrheal has declined since 1990, diarrhea remains as the third leading cause of mortality in children globally, after pneumonia and preterm birth complication. According to the CDC, diarrhea is the second leading cause of death and malnutrition in children <5 years and accounts for 11% child deaths globally (https://www.cdc.gov/healthywater/pdf/global/programs/globaldiarrhea508c.pdf; https://www.who.int/news-room/fact-sheets/detail/diarrhoeal-disease). IBS is yet another digestive disorder with worldwide prevalence reported in 10%–15% range. While about 40% of IBS patients experience mild IBS, 35% and 25% of patients experience moderate and severe forms of the disease, respectively (https://aboutibs.org/what-is-ibs/facts-about-ibs/statistics/). In the United States, IBS is estimated to affect 25 to 45 million people, with a higher prevalence reported in females (2/3rd) than males (1/3rd) (https://aboutibs.org/what-is-ibs/facts-about-ibs/). Hemorrhoids is a digestive disorder that commonly affects both males and females. The prevalence of hemorrhoids was reported to range from 6% to 16%, with an average of 11% globally (Sheikh et al., 2020). Hemorrhoids affect approximately 5% Americans, with