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Robin Saar

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Small Animal Microbiomes and Nutrition Comprehensive resource providing holistic coverage of the effect of body microbiomes on the health status of dogs and cats Small Animal Microbiomes and Nutrition offers new perspective on the prevention and treatment of common health conditions in dogs and cats that arise from or result in dysbiosis of the body's microbiomes, along with providing alternative first-line solutions of utilizing nutrients--less invasive procedures in comparison to prescription drugs to treat dysbiosis in the body's microbiomes. This practical manual guides the reader through body systems that are commonly influenced by the microbiota in the microbiomes as well as accompanying dietary recommendations. Initially, an overview of the body's microbiome including common terminology and functions of microbiomes precede the chapters on development of the body's microbiomes and factors influencing their diversity and density. The following three sections provide readers with a different perspective of commonly observed health conditions by focusing on the state of the microbiome and how the condition may be prevented and/or treated with the use of nutrients. Written by a highly qualified author with significant experience in the field, Small Animal Microbiomes and Nutrition includes information on sample topics such as: * Results of research on alternative diets and emerging ingredients' effect on the microbiomes and how to have the discussions with pet parents * Nutrition focused calculations, feeding directions, and templates for history, and recommendation for follow-up conversations with pet parents * Factors affecting the diversity and density of the microbiomes, such as genetics, age, sex, environment, stress, antibiotic therapy, and nutrition * Integumentary microbiomes, covering the skin's microbiome, dysfunctional barrier syndrome, atopy (atopic dermatitis), and key nutritional factors Small Animal Microbiomes and Nutrition is an essential resource for students completing companion animal health courses in two- and four-year programs, particularly those in veterinary technology, veterinary technician, and animal health technology diplomas and degrees, and it is also highly useful for students in other veterinary and animal science focused programs. Additionally, this book is essential in veterinary practices as a reference guide to support the transition into the utilization of microbiome medicine.

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Table of Contents

Cover

Table of Contents

Title Page

Copyright Page

Preface

About the Companion Website

Section I: Understanding a Microbiome

1 Common Definitions

1.1 Microbiome

1.2 Microbiota

1.3 Pathogens

1.4 Symbiosis

1.5 Dysbiosis

1.6 Probiotics

1.7 Prebiotics

1.8 Synbiotics

1.9 Biological Markers (Biomarkers) and Their Measurement

Glossary

References

2 Functions of the Gastrointestinal Microbiome

2.1 What Is the Gastrointestinal Microbiome?

2.2 Metabolic Functions

2.3 Structural Functions

2.4 Protective Functions

2.5 Participation in Bidirectional Axis Communication

2.6 Chapter Summary

References

3 The Origin and Development of the Gastrointestinal Microbiome

3.1 In Utero

3.2 Factors Influencing the Initial Colonization of Microbiota

3.3 Dysbiosis During Microbiome Development

3.4 Key Nutritional Factors

3.5 Chapter Summary

References

4 Factors Affecting the Diversity and Density of the Microbiomes

4.1 Physiological Factors

4.2 Pathophysiological Factors

4.3 Chapter Summary

References

5 Essential Nutrients and the Microbiota

5.1 Protein

5.2 Carbohydrates

5.3 Fat

5.4 Vitamins and Minerals

5.5 Processing and Digestibility of Nutrients

5.6 Chapter Summary

References

6 Current Methods for Microbiome Analysis

6.1 Introduction

6.2 Why is it Important to Characterize the Microbiome?

6.3 Sample Collection and Preservation Methods

6.4 Current Methods for Microbiome Analysis

6.5 Chapter Summary

References

7 Microbiome‐Centric Management of Dysbiosis

7.1 Key Nutritional Factors

7.2 Probiotics

7.3 Fecal Microbiota Transplantation

7.4 Bacteriophages

7.5 Chapter Summary

References

Section II: The Microbiome's Involvement in Body Systems

8 The Immune System

8.1 Innate and Adaptive Immunity

8.2 The Microbiome's Involvement in Immunity

8.3 Supportive Nutrients

8.4 Chapter Summary

References

9 The Endocannabinoid System

9.1 Endocannabinoid System

9.2 The Endocannabinoidome Axis

9.3 Chapter Summary

References

10 Respiratory System Microbiome

10.1 The Respiratory System Microbiome

10.2 Factors Affecting Diversity and Density

10.3 Diseases Associated with Dysbiosis

10.4 Key Nutritional Factors

10.5 Chapter Summary

References

11 Oral Microbiomes

11.1 The Oral Microbiome

11.2 Factors Affecting Diversity and Density

11.3 Diseases Associated with Dysbiosis and Inflammation

11.4 Key Nutritional Factors

11.5 Chapter Summary

References

12 Aural Microbiome

12.1 The Aural Microbiome

12.2 Factors Affecting Diversity and Density

12.3 Diseases Associated with Dysbiosis

12.4 Key Nutritional Factors

12.5 Chapter Summary

References

13 Integumentary Microbiomes

13.1 The Cutaneous Microbiome

13.2 Factors Affecting Diversity and Density

13.3 Diseases Associated with Dysbiosis

13.4 Key Nutritional Factors

13.5 Chapter Summary

References

14 Hepatic Circulation and Bile Acid Involvement with Microbiomes

14.1 Hepatic Circulation and Bile Acid Metabolism

14.2 Microbiota's Role in Bile Acid Metabolism

14.3 Bile and Bile Acids Fundamental Roles in the Regulation of Various Physiological Systems

14.4 Nutrients in Bile

14.5 Liver–Gut–Brain Axis

14.6 Bile Acid Dysmetabolism

14.7 Key Nutritional Factors

14.8 Chapter Summary

References

15 Gastrointestinal Microbiomes

15.1 The Gastrointestinal Microbiome

15.2 The GI Microbiome's Role in the Production of Vitamins

15.3 Conditions Affected by or Associated with the GI Microbiome

15.4 Chapter Summary

References

16 Neurological Interactions with Microbiomes

16.1 The Nervous System

16.2 The Gut–Brain Communication Axis

16.3 Anxiety

16.4 Cognitive Dysfunction

16.5 Psychobiotics

16.6 Nutrients

16.7 Chapter Summary

References

17 Urinary System

17.1 GI–Renal Axis

17.2 Urobiome

17.3 Defenses Against Urinary Tract Infections

17.4 Key Nutritional Factors

17.5 Chapter Summary

References

Section III: Emerging Ingredients and Alternative Diets

18 Raw Ingredient Diets

18.1 Raw vs Cooking

18.2 Comparing Extruded, Canned, and Raw

18.3 Antimicrobial Resistance

18.4 Fermented Products

18.5 Chapter Summary

References

19 Grain and Gluten‐Free Diets

19.1 Grains

19.2 Gluten

19.3 Chapter Summary

References

20 Cannabinoids

20.1 Regulations on Cannabis Products

20.2 By‐products of the Plant as an Ingredient Source

20.3 Concerns About the Health and Safety of Cannabis Products in Animal Feed

20.4 Cannabidiol Supplementation Effects on the Microbiome

20.5 Antimicrobial Effects of Cannabis

20.6 Current Diets on the World Pet Food Market

20.7 Chapter Summary

References

21 Insects

21.1 Black Soldier Fly Larvae

21.2 Heavy Metal and Mycotoxin Accumulation in Insects

21.3 Chitin

21.4 The Effects on the Host GI Microbiome

21.5 Chapter Summary

References

Section IV: Communication and Nutrition Plans for Pet Parents

22 Communicating with Pet Parents

22.1 From the Pet Parent Perspective

22.2 How the Brain Processes New Information

22.3 Improving Action Results

22.4 Supporting Pet Parents Through the Decision‐Making Process

22.5 Improving Conversations

22.6 Providing Continuing Support to Pet Parents

22.7 Chapter Summary

References

23 Documenting a Nutrition History

23.1 How to Ask the Right Questions

23.2 Nutrition Questionnaire

23.3 Chapter Summary

References

24 Dietary Treatment Plans

24.1 Pet Parents Want Veterinary Nutrition Recommendations

24.2 Increasing the Value of Nutrition Plans

24.3 Components of a Nutrition Plan

24.4 Chapter Summary

References

25 Calculations for the Nutrition Consultation

25.1 Energy Requirements

25.2 Calculating kcal/cup or kcal/can from Energy Requirement

25.3 Calculating kcal per day by Weight (grams)

25.4 Calculating Calories from Nutrients and Metabolizable Energy

25.5 Calculating Percentage of Body Weight Loss

25.6 Calculating Energy Requirements for a Critical Care Patient

25.7 Calculating Water Requirements

25.8 Calculating Metabolic Water

25.9 Feeding and Transition Plan Formulations

25.10 Creating a Feeding Plan

25.11 Chapter Summary

References

Index

End User License Agreement

List of Tables

Chapter 1

Table 1.1 Common canine and feline pathogens.

Table 1.2 Examples of symbiotic relationships.

Table 1.3 Dysbiosis‐associated conditions in humans.

Chapter 2

Table 2.1 Short chain fatty acids (SCFA), their main roles in the body, and ...

Chapter 4

Table 4.1 Age difference on the stability and changes in the microbiome.

Chapter 5

Table 5.1 Functions of vitamins on the GI microbiota.

Chapter 6

Table 6.1 Current methods used to characterize the microbiome

Chapter 10

Table 10.1 Sources and common microbes found in primary and secondary bacter...

Chapter 11

Table 11.1 Common diseases of the oral cavity and the niches affected.

Chapter 15

Table 15.1 Common bacterial components of the gastrointestinal microbiome....

Chapter 18

Table 18.1 Examples of gram negative bacteria and their actions.

Chapter 25

Table 25.1 Legend conversion chart.

List of Illustrations

Chapter 1

Figure 1.1 Definitions of probiotics, prebiotics, and synbiotics.

Figure 1.2 The five metabolites derived from the gut microbiota and their ma...

Chapter 2

Figure 2.1 Contribution of microbiota to amino acid synthesis. While most am...

Figure 2.2 The protective functions of microbiota.

Chapter 3

Figure 3.1 Factors influencing the initial colonization of microbiota.

Figure 3.2 (a) Heatmap depicting the shift of predominant bacterial phyla. P...

Figure 3.3 Stem cell populations and long‐term physiology are impacted by ch...

Figure 3.4 Postweaning considerations for using different supplements.

Chapter 4

Figure 4.1 The seven factors affecting the diversity and density of the micr...

Figure 4.2 Monozygotic twins show more microbial similarity, compared to diz...

Figure 4.3 Effects of antibiotic therapy on the microbiota.

Chapter 5

Figure 5.1 Factors affecting the GI microbiota. Finding a balance with these...

Figure 5.2 Carbohydrate categories and molecular composition.

Figure 5.3 Fermentability and solubility range of fiber and complex carbohyd...

Chapter 6

Figure 6.1 Illustration of conserved, variable, hypervariable regions within...

Figure 6.2 Current techniques used to characterize and analyze microbial com...

Chapter 7

Figure 7.1 Fecal microbiota transplantation can be performed with two differ...

Chapter 8

Figure 8.1 Components of the innate and adaptive immune responses.

Figure 8.2 Intestinal permeability in a healthy host and an afflicted host. ...

Figure 8.3 Supportive nutrients for the microbiota and their effect on the i...

Chapter 9

Figure 9.1 Change in endocannabinoid and cortisol levels in response to stre...

Figure 9.2 The state of the endocannabinoidome is closely associated with th...

Figure 9.3 Effect of the GI‐microbiome – endocannabinoid axis on behavioral ...

Figure 9.4 Example of an obese cat.

Chapter 10

Figure 10.1 Bacterial diversity in the oropharyngeal (OP) and bronchoalveola...

Figure 10.2 Nasal samples from cats in different ages, environments, and hea...

Figure 10.3 Changes in the respiratory tract microbiota can lead to common d...

Chapter 11

Figure 11.1 Distribution of bacterial taxa found in the canine oral niches....

Chapter 12

Figure 12.1 Factors that can cause change in the microbiota diversity found ...

Figure 12.2 Disease progression from acute, with planktonic bacteria, to chr...

Figure 12.3 Beginning stages of otitis externa. Note increased debris soon t...

Figure 12.4 Aural microbiome diversity is decreased when the patient becomes...

Chapter 13

Figure 13.1 The normal core skin microbes found on dogs and cats.

Figure 13.2 Figure (a) lists the most commonly diagnosed skin diseases in ca...

Figure 13.3 Functions of a normal skin barrier. If any one of these is disru...

Figure 13.4 Atopy pathway showing how disruption in the gut can lead to hype...

Chapter 14

Figure 14.1 Recycling of bile acids.

Figure 14.2 Four main pathways of transformation of bile acids by microbiota...

Figure 14.3 Liver–gut–brain axis (simplified) and associated disorders when ...

Figure 14.4 Domino effect on the bile recycling system that occurs when ther...

Chapter 16

Figure 16.1 The gut–brain axis. There is bidirectional communication between...

Figure 16.2 Benefits and actions of gastrotransmitters on the host.

Figure 16.3 Attributing factors and process of cognitive dysfunction syndrom...

Figure 16.4 The benefits of psychobiotics on the central nervous system of t...

Chapter 17

Figure 17.1 The gut–kidney axis. Endogenous metabolites dysregulation and gu...

Figure 17.2 Different methods of microbial identification in urine samples....

Figure 17.3 Risk factors for contracting a urinary tract infection.

Figure 17.4 Key elements in natural defenses against UTIs.

Chapter 18

Figure 18.1 The mean true fecal digestibility of meat proteins when prepared...

Figure 18.2 Heatmap showing the abundance of metabolites found in fecal samp...

Figure 18.3 WHO list of antibiotic‐resistant pathogens listed in three categ...

Chapter 19

Figure 19.1 The three main physiological benefits of grains on the GI microb...

Chapter 20

Figure 20.1 Results of the addition of the CBD supplementation.

Chapter 21

Figure 21.1 Advantages of using Black Soldier Fly Larvae as a protein source...

Figure 21.2 Main bacteria relative abundance found in cecal samples of broil...

Chapter 22

Figure 22.1 The four elements of the protection motivation theory (PMT).

Figure 22.2 Elements of an efficient action plan.

Figure 22.3 Concept map of a logical flow of decision‐making expectations an...

Figure 22.4 Benefits of providing emotional validation to the pet parents.

Chapter 23

Figure 23.1 Types of questions and responses.

Chapter 24

Figure 24.1 Components of a nutritional plan.

Chapter 25

Figure 25.1 Graph depicting differences between linear and body surface area...

Guide

Cover Page

Title Page

Copyright Page

Preface

About the Companion Website

Table of Contents

Begin Reading

Index

Wiley End User License Agreement

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Small Animal Microbiomes and Nutrition

Robin Saar

RAS4Pets

Lethbridge

AB, Canada

Sarah Dodd

University of Guelph

Garafraxa

ON, Canada

Copyright © 2024 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey.Published simultaneously in Canada.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per‐copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750‐8400, fax (978) 750‐4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748‐6011, fax (201) 748‐6008, or online at http://www.wiley.com/go/permission.

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Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

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Library of Congress Cataloging‐in‐Publication DataNames: Saar, Robin, author. | Dodd, Sarah (Veterinary nutritionist) author.Title: Small animal microbiomes and nutrition / Robin Saar, Dr. Sarah Dodd.Description: Hoboken, NJ : Wiley‐Blackwell, 2024. | Includes bibliographical references and index.Identifiers: LCCN 2023002572 (print) | LCCN 2023002573 (ebook) | ISBN 9781119862604 (paperback) | ISBN 9781119862635 (adobe pdf) | ISBN 9781119862628 (epub) | ISBN 9781119862611 (obook)Subjects: MESH: Animal Nutritional Physiological Phenomena | Pets–physiology | MicrobiotaClassification: LCC SF414 (print) | LCC SF414 (ebook) | NLM SF 414 | DDC 636.089/32–dc23/eng/20230523LC record available at https://lccn.loc.gov/2023002572LC ebook record available at https://lccn.loc.gov/2023002573

Cover Design: WileyCover Images: Courtesy of Robin Saar

Preface

Microorganisms coexist in communities everywhere, soil, plants, oceans, and as a part of animals’ physiological systems. What is interesting is the essential and intrinsic roles the microbiota in these communities play in the health and function of the environment in which they reside. Researchers in the field now recognize the gut microbiome as a super organ in the body as it completes or assists in multiple normal physiological and metabolic processes. This super organ influences and co‐functions within the body of animals, and we are just starting to peel away the layers of how the microbiota influence animal health.

Nutrition has historically taken a back seat in veterinary education and client conversations. Recently, pressure from pet parents to receive our recommendations and guidance on the best nutrition for their pets has invigorated the nutrition education sector. Nutrition goes hand in hand with the gut microbiome; nutrients not absorbed in the small intestine continue to the large intestine and undergo microbial fermentation. The results of these interactions influence both microbial and host health. Currently, we design diets to meet the pet’s nutritional needs and rarely consider the health of the gut microbes or the resulting influence when formulating a diet. Nutritional knowledge, diet varieties, and pet parent willingness to participate in their pet’s health has also increased in the last decade, evoking the need for veterinary professionals to evolve how they practice nutritional medicine and engage with pet parents.

This textbook’s final chapters review basic nutritional math equations, practical tips, and best practices when communicating with pet parents. In my experience, communication with pet parents is the most substantial skill a veterinary professional must master to be successful.

While there is a growing aggregate of research papers in this field of study, a textbook providing an all‐encompassing practical guide for all veterinary professionals did not exist, until now. Microbiome medicine is not part of veterinary or veterinary technology curricula to the extent that it should be. I wanted to provide a practical guide that would review the normal physiological processes in such a manner that anyone with a basic understanding of animal physiology could comprehend and create a practical application within a veterinary practice. While we need further research in this vast field, and I acknowledge that a few of these concepts require a deeper dive, I feel that this format will provide an introductory learning platform about microbiomes in dogs and cats. This topic is in its infancy, and I am excited to provide vet professionals with an introductory textbook on small animal microbiomes and nutrition.

Finally, I acknowledge Dr. Holly Ganz, Dr. Dawn Kinsbury who wrote chapters 5 and 6 and Nicole Stevens and Andrew Abernathy who added figures and tables.

About the Companion Website

This book is accompanied by a companion website.

www.wiley.com/go/saar/1e 

This website includes chapter 26.

Section IUnderstanding a Microbiome

1Common Definitions

1.1 Microbiome

There are multiple functional definitions of the term “microbiome.” According to the Human Microbiome Consortium, the microbiome is considered as the community of all microbes recovered from a particular habitat or ecosystem [1]. These microscopic communities, including bacteria, fungi, and viruses, can be found in all living things, including plants, and are found in every different imaginable habitat, from lifeforms to soils and bodies of water [2, 3]. Microbiomes can be found on outer surfaces, particularly as biofilms, and within several body systems of animals including the respiratory tract, reproductive organs, integumentary, oral cavity, urinary tract, neurological pathways via the brain‐gut axis, and the gastrointestinal (GI) tract. Over 30 trillion microbes may reside within the GI system alone [4, 5]. This list is not exhaustive, as this area of knowledge is relatively novel, and innovations allow us to discover microbiomes in organs and systems once thought to be sterile. The total cumulative microbiomes in a human host may weigh as much as 1–3% body mass [4].

While some common trends are being observed in current research, microbiomes are unique for each individual with their diversity and density affected by several intrinsic (genetics, age, sex) and extrinsic (environment, physiological state, antibiotic therapy, health and nutrition) factors [6]. These incredibly diverse communities shape the health of the host and influence its physiology, through multiple complex pathways, including influencing remote organ and immune responses. A main focus of research is on the microbiomes of the GI tract, and how perturbations of these complex communities are associated with multiple health conditions in humans: depression, autism spectrum disorder, oral health, chronic obstructive pulmonary disease (COPD), asthma, pneumonia, dermatological, obesity, cardiovascular, diabetes, rheumatoid arthritis, hepatic associated disorders, cancer, inflammatory bowel disease (IBD), and infection due to bacterial translocation [4–7]. Microbiome communities affect the status of, and rely on, each other for daily functions, communicating through the release of metabolites – products of microbial fermentation [8]. One recognized influence is the cumulative genetic material, the metagenome, of all the microbes in one animal's singular microbiome. A metagenome may contain over 200 times the number of genes in a host's genome; therefore, the level of influence these genes have over host gene expression is one explanation for the microbiota influence on the host's physiological systems [8].

The development of new innovative research tools allows us to see, understand, and evaluate previously unidentifiable concepts regarding the body's microbiomes. Some obstacles that remain with identifying and determining the effects of microbiomes are reproducing their environment, including food sources, to enhance growth and preventing the death of the microbes when sampling. Research is also limited at this time, with many research projects utilizing small study groups, which are not always representative of the wider population, or reproducible in future projects. This is a common limitation for quantitative research [9].

1.2 Microbiota

The microbiota may be defined as the individual bacteria, fungi, viruses, and protozoa that can be found in a microbiome community. Microbes pre‐date the Earth's eukaryotic biodiversity and are numerous, diverse, and ubiquitous. They have adapted to live in extreme environments such as the high pressure, as in the deep ocean, extreme heat, or chemical exposure. Different types of bacteria survive in both aerobic and/or anaerobic environments. Environmental differences are one reason that it has been difficult to identify microbiota in discovered and undiscovered communities [8]. Those that live in an anaerobic environment may have a shorter survival rate when removed, for example in biopsy samples, and then brought into an aerobic environment. It is estimated that only 20–30% of organisms are culturable, which leaves a large group of microbiota that are unidentified through routine culture [10]. The main phyla composing the gut microbiome vary from species to species, but Fusobacteria, Bacteroidetes, and Firmicutes, as well as, to a lesser extent, Proteobacteria and Actinobacteria, are typically prevalent in dogs and cats [3, 11].

Communication occurs between the microbes within their microbiome and with host body systems, which in turn can change or influence the physiology of the host. The host relies on the microbiota to complete functions that may not be encoded in their genes to complete [5]. The roles of microbiota are complex and may change as resource availabilities change [8]. Currently, we understand that microbiota plays roles in the production of vitamins, mineral absorption, structural integrity of barriers, metabolism of nondigestible products and provision of energy sources (short‐chain fatty acids – SCFAs), interactions with or involved in the production of chemical and neurotransmitter metabolites affecting other organs of the body (bidirectional axis), host genomic expression, inflammatory processes, intestinal permeability, immune function, and food intake and energy expenditure [4, 6, 8, 11–16].

1.3 Pathogens

Pathogens are defined as a biological agent that causes disease or illness to its host. Although in the minority, these microbes are generally known to cause illness, at least in certain circumstances. Pathogens can be divided into five groups: viruses, bacteria, fungi, protozoa, and helminths [17]. Characteristics of pathogens are the mode of transmission, mechanism of replication, pathogenesis (how it causes diseases), and ability to elicit a response. Depending on the pathogen, replication may occur in the intracellular and/or extracellular compartments, while host defense mechanisms work to destroy the pathogen and stop its growth. Common canine and feline pathogens are summarized by group in Table 1.1.

Pathobionts are commensal microbes that can be present at low levels in healthy microbiomes without causing harm to the host but can be pathogenic under certain circumstances [10]. While a general previous concept was a simple overgrowth of a pathogenic bacteria was the cause of dysbiosis, new information shows that a barrier dysfunction plays a larger role in pathogenic bacteria being allowed to either colonize or translocate (cross the surface of an epithelial barrier) causing illness in the host [10, 17]. In some circumstances, it may be a combination of genetics along with the presence of specific microbiota or metabolites that lead to disease or illness in the host. The immune response cannot eliminate most pathogens, and most pathogens are not universally lethal as this would affect the long‐term survival of that pathogen [17]. However, some pathogens may cause an attack on the immune response that can affect other microbiomes in the body and may be detrimental for the host [25, 26].

Table 1.1 Common canine and feline pathogens.

Source: Adapted from Alexander et al. [18], Inpankaew et al. [19], Day et al. [20], Riley et al. [21], Millán and Rodriíguez [22], Biek et al. [23] and Villeneuve et al. [24].

Common causes of disease in dogs and cats

Viruses

DNA viruses

Adenoviruses

Canine adenoviruses

Herpesviruses

Canine herpesvirus

Feline herpesvirus

Parvoviruses

Canine parvovirus

Feline panleukopenia virus

RNA viruses

Orthomyxoviruses

Canine influenza

Paramyxoviruses

Canine distemper virus

Canine parainfluenza virus

Coronaviruses

Canine respiratory coronavirus

Feline enteric coronavirus

Picornaviruses

Feline calicivirus

Rhabdoviruses

Rabies

Retroviruses

Feline leukemia virus

Feline immunodeficiency virus

Bacteria

Gram +ve cocci

Staphylococci

Staphylococcus

spp.

Streptococci

Streptococcus

spp.

Gram −ve cocci

Bartonella henselae

Gram +ve bacilli

Corynebacteria

Bacillus anthracis

Listeria monocytogenes

Gram −ve bacilli

Bordetella bronchiseptica

Yersinia pestis

Anaerobes

Clostridia

Clostridia

spp.

Spirochetes

Borrelia burgdorferi

Leptospira interrogans

Rickettsials

Ehrlichia canis

Anaplasma

spp.

Chlamydias

Chlamydophila felis

Mycoplasmas

Mycoplasma haemocanis

Mycoplasma felis

Fungi

Candida albicans

Cryptococcus neoformans

Aspergillus

Histoplasma capsulatum

Coccidioides immitis

Protozoa

Giardia

spp.

Leishmania

Babesia

spp.

Hepatozoon canis

Cystoisospra

Cryptosporidium

Toxoplasma gondii

Helminths (worms)

Nematodes (roundworms)

Dirofilaria immitis

Toxocara

spp.

Toxascaris leonina

Uncinaria stenocephala

Trichuris vulpis

Ancylostoma

spp.

Capillaria

spp.

Cestodes (tapeworms)

Taenia

spp.

Echinococcus

spp.

Sarcocystis

1.4 Symbiosis

Symbiosis describes a relationship or interaction between two organisms of different types, and the specific classification of symbiosis depends on whether either or both organisms benefit from the relationship [27]. These different species inhabit the same spaces and share or compete for the same resources. They interact in a variety of ways, known collectively as symbiosis. There are five main symbiotic relationships: mutualism, commensalism, predation, parasitism, and competition. Table 1.2 shows examples of each.

Mutualism – All species benefit from positive effects focusing on protection from pathogens and/or the provision of nutrients

[28]

. An example of mutualism is the dependence of symbionts (microbiotas) on resources (cellulose) that are not utilized by the host. Another example is

Bifidobacterium longum

(subspecies

infantis

B. infantis

), which is found in human breast milk. This breast milk contains 30% of calories coming from oligosaccharides that cannot be digested by the infant and are instead digested by

B. infantis

in the GI tract.

Bifidobacterium

and

Lactobacillus

are generally regarded as beneficial microbes because of their ability to exclude harmful bacteria by producing various antimicrobial agents

[26]

.

Predation – One species benefits from consuming another species. When looking for means to precisely modulate microbiomes, predation is being researched as a promising approach

[29]

. Bacteriophages (phages) are viruses that prey on bacteria

[30]

. Phages can enter a bacterium and rapidly multiply producing hundreds of new viruses. Benefits of using predation as an approach in modulating microbiomes are the ability to (i) deliberately perturb specific bacteria, (ii) develop a deeper understanding of interbacterial and bacterial‐mammalian host interactions, and (iii) be able to plan and create reproducible approaches to remodel microbiota for therapeutic purposes

[29]

.

Table 1.2 Examples of symbiotic relationships.

Source: Adapted from Swain Ewald and Ewald [28].

Strongly positive

Obligate mutualism

Lichen

Strong mutualism

Most vertically transmitted gut mutualists and their host

Moderate mutualism

Clownfish and anemones

Marginal mutualism

Ants and aphids

Neutral

Commensalism

Clown fish and anemones

Benign parasitism

Dipylidium caninum

and canids

Conspicuous parasitism

Many GI nematodes and their host

Severe parasitism

Parvovirus and their host

Strongly negative

Lethal parasitism

Dirofilaria immitis

and their host

Parasitism – One species benefits from living with, on, or in a host species at the expense of the host. Some negative effects of parasitism are vitamin deficiency, immunopathy, tissue damage, and mortality

[28]

. While parasitism is generally thought of to have a negative effect, there are some instances where utilization of select organisms may induce a more positive effect on the host, particularly in chronic infections. In mice, chronic intestinal helminth infection has been documented to increase susceptibility to co‐infection, and lower the efficacy of vaccination, while also downregulating allergic immune responses to harmless antigens creating protection against allergic diseases [

29

,

31

].

Competition – Different species benefit from limited resources in the same ecosystem at the expense of each other. Competition exclusion is a common trait of some probiotics. These nonpathogenic bacterial cultures are used to reduce colonization or decrease populations of pathogenic bacteria

[32]

. Competitive exclusion for intestinal bacteria is the bacteria to bacteria competition for available nutrients and mucosal adhesion sites

[33]

. They can also change the environment to make it less suitable for their competitors. Bacteria may also displace pathogens by taking up space in the biofilm or mucosa, inhibit the adhesion of pathogens, and decrease the competitor's ability to attach to receptor sites. The level of effectiveness of a bacterium using this relationship depends on the strain, species, and genus to receive reproducible results. Another form of competition exclusion is the production of debilitating metabolites by beneficial bacteria. Bacteriocins are one example of antimicrobial metabolites, which affect the pathogens but not the bacteriocins themselves. There are three main classes of bacteriocins based on their structure and function

[34]

:

Class I – small peptides possessing lanthionine residues

Class II – which is heat‐stable and does not contain lanthionine residues

Class III referred to as bacteriolysins – which are large, heat‐labile murein hydrolases

Commensalism – One species benefits with no net positive or negative effect to the other

[35]

. Many discussions about the microbiota in microbiomes regard the relationship between the host and the microbiota to be commensal. This term when used in a simplistic definition does not consider the complexity of these relationships. One paper describes commensalism as the dividing line between parasitic and mutualistic associations, with the overall effects of this relationship as being positive or negative, difficult to accurately assess

[28]

. Additionally, because these effects are not able to be precisely measured, it is difficult to always place microbiota appropriately on this continuum of mutualistic to commensal to parasitic. This group of microorganisms is called indeterminate symbionts. There are situations where some bacteria can move from being mutualistic to parasitic in different circumstances. These ambisymbionts can be identified as either mutualistic or parasitic, whereas indeterminate symbionts have an uncertain net effect.

Positive “commensal relationships” are providing the host with essential nutrients, metabolism of indigestible compounds, protection against colonization of opportunistic pathogens, contribution to the development of the intestinal architecture, and stimulation of the immune system [36] (Box 1.1).

Box 1.1Positive Effects of Host–Symbiote Relationship

Providing the host with essential nutrients

Metabolism of indigestible compounds

Protection against colonization of opportunistic pathogens

Contribution to the development of the intestinal architecture

Stimulation of the immune system

1.5 Dysbiosis

If there is a microbial shift, brought on by genetics of the host, infectious illnesses, diets, or the prolonged use of antibiotics or other bacteria‐destroying medications, these perturbations to the structure of the community is referred to as dysbiosis [10, 37]. When this occurs, normal interactions stop, resulting in the host body being more susceptible to disease [10]. Perturbation of normal host microbiota has been associated with several pathologies in dogs and cats, including chronic enteropathies, idiopathic IBD, acute hemorrhagic diarrhea syndrome, small bowel strictures or adhesions, neoplasia, chronic intussusception, hypothyroidism, diabetic autonomic neuropathy, scleroderma, abnormal migrating motor complexes, atrophic gastritis, and exocrine pancreatic insufficiency [3]. Table 1.3 lists some dysbiotic conditions recognized in humans.

Three types of dysbiosis can occur concurrently [10]:

Loss of beneficial microbial organisms – There are several mechanisms where commensal bacteria can positively influence host biology to prevent disease. Beneficial microbiota influences the host immune response with the tolerance of resident commensals being governed in part by T regulatory (Treg) cells, which are a specialized subset of T lymphocytes. When beneficial microbiota ferments dietary products, they can produce SCFAs, which have been shown to regulate the Treg pool to protect the body from inflammation and disease states such as colitis. Beneficial bacteria may also directly reduce inflammation by targeting cytokines and play a role in regulating invariant Natural Killer T cells (NKT) cells, which influence lipid antigens along with innate and adaptive inflammation.

Table 1.3 Dysbiosis‐associated conditions in humans.

Source: Adapted from DeGruttola et al. [38] and Sudhakara et al. [39].

Periodontal disease

Neurological diseases – depression/anxiety

Respiratory diseases

Dermatological diseases

Obesity

Diabetes

Arthritis and joint diseases

Inflammatory bowel diseases

Allergic diseases

Autism

Expansion of pathobionts – Pathobionts may create harmful effects when given the opportunity to expand. Multiple studies have demonstrated how pathobionts can increase their numbers by taking advantage of an inflamed environment. For example, when animals are treated with antibiotics, then have colitis induced using dioctyl sodium sulfosuccinate, a multi‐drug‐resistant stain of

Escherichia coli,

increases in numbers and can penetrate the intestinal mucosal barrier and translocate causing sepsis.

Loss of diversity – With multiple varieties of microbiota eliciting health benefits to the host, having a more diverse and complex pool of organisms has been shown to provide maximum benefits. Some studies have observed a difference in disease processes later in life associated with lower microbial diversity at a crucial development stage.

1.6 Probiotics

The Food and Agriculture Organization of the United Nations and the World Health Organization defined a probiotic as “live microorganisms, which when administered in adequate amounts, confer a health benefit upon the host” [40, 41]. Probiotics in the form of cultured and fermented food sources (examples: yogurt, sauerkraut) have been anecdotally known to have health benefits, with research now looking at specific microbiota strains, species, and subspecies of bacteria, correlating them with direct benefits via commensal interactions with the GI tract resident microbiota [42]. Probiotics may be utilized to manage GI dysbiosis and have been shown in some cases to strengthen the immune response. Some probiotics can stimulate the production of anti‐inflammatory substances and may participate in communication with other organs via bidirectional communication [42] (Figure 1.1).

There are characteristics of probiotics that allow them to be beneficial:

The microbiota in the probiotic must be alive and viable at the time of consumption [

40

,

43

].

It must be able to survive varying environments through GI transit including gastric acid and be resistant to digestion by intestinal enzymes [

40

,

43

].

The probiotic being used should be considered safe [

40

,

43

].

Probiotics must either enhance the commensal bacteria or suppress the growth or colonization of pathogenic bacteria. There are three main actions through competition and exclusion that probiotics protect the host from pathogenic bacteria:

Bacteria to bacteria competition for available nutrients

[32]

Competition for space and acting as a physical barrier prevent pathogens from attaching to the gut surface [

33

,

43

] – the action of the probiotic bacteria may be to adhere to the intestinal epithelia or receptors of the GI tract preventing the colonization of pathogenic bacteria

Figure 1.1 Definitions of probiotics, prebiotics, and synbiotics.

Secretion of antimicrobial metabolites or mediators such as bacteriocins [

34

,

43

]

The result of giving a probiotic should enhance the overall health of the pet. One example of positive action is the fermentation of undigested nutrients resulting in the production of SCFAs [

44

,

45

]. SCFAs nourish enterocytes, increasing the health of the intestinal wall. SCFAs when produced in larger volumes can lower intestinal pH inhibiting the growth of pathogenic bacteria that prefer a more alkaline environment.

The main uses of probiotics are to:

Promote a positive change in a GI microbiome – utilizing the actions listed above the probiotic microbiota may elicit a change back to the host's normal diversity and density of microbiota

[45]

.

Stimulate or enhance an immune response, without being proinflammatory – the modulation of the host GI immune system both locally and systemically via their interaction with the resident microbiota, GI epithelia, and gut immune cells [

43

,

46

].

Increase or stimulate the production of neurochemicals and interaction

with the gut‐brain axis [47]. Probiotics that act as psychobiotics are utilized to affect many neurochemical disorders such as anxiety in pets.

Modulation of the immune system, help in stress management, protection from infection, improve growth and development, control allergies, and manage obesity

[44].

There are times when the use of probiotics is possibly contraindicated. In an instance where a pet has a compromised GI barrier (barrier dysfunction), it is not recommended to take oral dosages of probiotics (live bacteria) as there is a rare, yet severe risk of bacterial translocation and sepsis, particularly in unregulated products [48].

In North America, as long as the probiotic label does not indicate any health claims, probiotics are not considered to be pharmaceuticals, and the classes of nutraceuticals or supplements are not recognized for animals and therefore do not have the same regulations placed upon them as pharmaceuticals, with regards to viability studies, dosing, and expiry of products. This lack of regulation could result in inconsistencies in the product contents with concerns that:

The product is not what is indicated on the label

[49].

The bacteria may not be viable or in an carrier promoting survival to the target location

[44].

The product may not provide benefits and may be pathogenic

[37

,

44

,

49].

The bacteria are not listed at the subspecies level and may not result in the same or any benefits for the host

[37].

The product may not contain sufficient bacteria to elicit a change

[50]

.

The product may not be tested to identify the specific genus and dosage, nor have been tested for safety, stability, and consistent positive results

[37

,

50].

The strain used may release harmful metabolites

[43].

The strain may be prone to transmit antibiotic resistance

[44

,

51].

Bacterial translocation may result in infection

[44

,

48].

1.7 Prebiotics

As opposed to probiotics, which consist of viable organisms, prebiotics are nutrients predominantly undigestible by the host animal that serve as a food source to be metabolized by the microbiota, resulting in benefit to the host [40, 45, 52]. These food sources consist of nutrients that can be fermented by the microbiota, which increases the survivability of beneficial microbes. Each species of microbiota has preferential food sources. Sources of indigestible nutrients are mainly from carbohydrates, with psyllium husk and/or yeast cell walls being a common ingredient used in commercial prebiotics at this time. As microbiota ferment cellulose, they may create the metabolites butyrate and acetate, SCFAs that are energy sources for colonocytes, and provide multiple other beneficial effects [44, 45].

To be classified as a prebiotic, the substrate must meet certain criteria [53]:

Resistant to digestion – does not break down in the acidic pH of the stomach, cannot be hydrolyzed by digestive enzymes, and is not absorbed in the upper GI tract.

Fermentable – it is fermentable by intestinal microbiota.

Produces a positive result – there is selective growth and/or activity of the intestinal microbiota that conveys a health benefit to the host.

There are different types of prebiotics: oligosaccharides like fructo‐oligosaccharide (FOS), oligofructose, mannose‐oligosaccharide (MOS), galacto‐oligosaccharide (GOS), pectic oligosaccharide (POS), inulin, and glucan and noncarbohydrate compounds such as flavanols. Fructans, pectins, inulin, and flavanols are predominantly derived from vegetation like fruits and vegetables, GOS can be derived from lactose or synthetic lactulose, and resistant starches and glucan may be derived from plants and yeast cells [53].

1.8 Synbiotics

Compounds comprising of a mixture of both live microorganisms (probiotics) and a substrate selectively utilized by beneficial microorganisms that confer a health benefit to the host (prebiotic) are termed synbiotics [54]. The International Scientific Association for Probiotics and Prebiotics (ISAPP) has created another class of synbiotics called synergistic synbiotics, defined as “a synbiotic for which the substrate is designed to be selectively utilized by the co‐administered microorganisms” [54]. These terms should be reserved for products where the prebiotic will selectively favor the specific probiotic organisms.

Reasons to feed a specific prebiotic with the probiotic are to [53]:

Selectively support the growth of the preferred microbiota once in the desired location (GI tract)

Aid in the metabolism of one or more health‐promoting bacteria

1.9 Biological Markers (Biomarkers) and Their Measurement

Biomarkers are cellular, biochemical, or molecular indicators detectable in biological media that suggest changes to normal or pathological processes, as well as responses to a therapeutic intervention [55]. When assessing a healthy patient or a patient experiencing a disease state, biomarkers as a tool can aid in the prediction, cause, diagnosis, progression, regression, or outcome of treatment. Biomarkers can be divided into Exposure, where the level of risk is predicted, and Disease, where screening, diagnosis, and progression are monitored (Chart slide 13). The methods of detection and measurement of biomarkers can also be divided into targeted or untargeted, depending on the aim of the study [56]. When relationships between specific biomarkers and outcomes are known, they are typically measured by targeted processes, meaning quantitative measurements of specific metabolites are made. Alternatively, untargeted approaches allow for a more discovery‐based approach, where a potentially vast number of individual or classes of biomarkers may be measured.

1.9.1 Genes, the Genome, and Genomics

The genome is the complete set of deoxyribonucleic acid (DNA) bearing all the genetic information of an organism [57]. The genes encoded in the DNA provide instructions to the cell on how to make each specific protein, which is then utilized to carry out functions in the body.

Proteins are synthesized through two processes:

Transcription – the synthesis of DNA into functional forms of ribonucleic acid (RNA), including mRNA, tRNA, rRNA, and noncoding RNA, which are used in the translation process.

Translation – the synthesis of mRNA into an amino acid sequence. The final polypeptide chain can then further undergo post‐translation modifications along with subsequent enzymatic and nonenzymatic alterations to increase the number of protein species.

Genomes are complex and can be influenced by environmental factors. The microbiome and their respective genome have been shown to play a major role in human health and disease.

Genome‐wide association studies (GWAS) is a scientific collaboration to create a large database to look for similar variants across the human genome, intending to determine links between genotypic and phenotypic variabilities [58]. Microbiome genome‐wide association studies (mGWAS) explain the interaction of host genetic variation with the microbiome.

Genomics refers to the study of an organism's genome, the entire complement of genes, including interactions between genes with both each other and the organism's environment [59, 60]. This may include analysis of all nucleotide sequences in the genome, and the structure, function, evolution, and mapping of the genome, in order to understand the entire genetic information of the organism. Next‐generation sequencing technology enables the investigation of the complex interaction between host genetics and microbial communities [58].

In comparison to genomics that study the genome of a singular organism, metagenomics is the study of a collection of genomes from a community of organisms [61]. This platform may be used to examine all DNA sequences across multiple organisms, particularly useful when culture or separation of microbes is not feasible or required.

Lastly, epigenetics refers to the study of how internal and external factors can influence the expression of genes [62–64]. Epigenetic changes are reversible and do not alter the sequence of DNA, or genotype, but instead affect the way the encoding of the DNA is interpreted – the phenotype.

Three ways epigenetics can affect gene expression are:

DNA methylation – a chemical group is added to a specific place on the DNA where it “blocks” the proteins “read” the gene [

63

,

64

]. The chemical group can then be removed by a process called demethylation. To “silence” or turn genes “off,” methylation is used while demethylation turns genes “on.”

Histone (chromatin) modification – histones are proteins that allow or stop DNA from being “read” depending on how tightly the DNA is wrapped around it

[64]

. Chromatin is the complex of histones and DNA combined. Chemical groups are added or removed from histones to alter the wrap. A wrapped gene is considered “off,” while an unwrapped gene is considered “on” or able to be “read.”

Noncoding RNA – while coding RNA is used to make proteins, noncoding RNA helps control gene expression by attaching to and breaking down coding RNA so it cannot be used to make proteins

[63]

. Noncoding RNA can also modify histones with the use of other proteins to influence whether the gene is “on” or “off.”

Epigenetics can change as part of growth and development, with some changes being reversible. These changes can affect an organism's health by affecting the immune system, developing neoplasia due to mutations, and affecting fetal epigenetics based on the maternal environment and behavior during pregnancy [64]. Known associated illnesses include cognitive dysfunction, respiratory, cardiovascular, reproductive, autoimmune, neurobehavioral illnesses along with a wide variety of behaviors and cancers. Epigenetic modifications can be induced by several drivers, including exposure to toxins, nutrition during pregnancy and early development, and behavioral influences such as maternal‐neonatal care, mental health, and the aging process.

1.9.2 Metabolites, the Metabolome, and Metabolomics

Microbial metabolism and fermentation results in production of small molecular substrates, intermediates, and products, collectively termed metabolites [65]. The vast diversity of metabolites are produced by microbiota from the metabolism or fermentation of macronutrients and micronutrients, which then can interact with multiple body systems. The effect of specific microbiota‐derived metabolites depends on multiple factors including the strain of microbiota, the food source provided, the volume of metabolites produced, and the health status of the host (Figure 1.2).

Figure 1.2 The five metabolites derived from the gut microbiota and their main function.

There are currently 5 gut microbiota‐derived metabolites identified:

Bacteriocins – A protein metabolite that has antimicrobial effects and works synergistically with beneficial bacteria to inhibit potentially harmful bacteria. The synergy of bacteriocins and antibiotics may help address the problem of antimicrobial resistance as a future approach in the treatment of infectious diseases

[34]

.

Short‐chain fatty acids – Indigestible carbohydrates such as some fiber sources are hydrolyzed by anaerobic bacteria into oligosaccharides that are then converted into phosphoenolpyruvate (PEP) and finally into acetic acid, butyric acid, and propionic acid depending on the bacteria of origin

[66]

. These metabolites in particular have been highly studied for their effect on the host

[45]

.

Microbial amino acids – While most amino acids in the intestines originate from the consumption of nitrogenous ingredients (animal and plant sources along with from the host muscle tissue), a small portion is synthesized

de novo

by the gut microbiota. A few bacteria can make all 20 of the standard amino acids, contributing to the host's amino acid homeostasis

[66]

. Microbial synthesized lysine, in particular, has been shown to contribute 2–20% of the total circulating volume in a study in humans, pigs, and rats.

Vitamins – Some vitamins can be completely synthesized by the gut microbiota including multiple B vitamins and vitamin K, which have benefits at improving immune health for the host – though sites of production and absorption must be considered

[67]

.

Quorum‐sensing autoinducers – Over time there is a gradual and accumulative increase in bacteria concentrations in a certain area. The bacteria will self‐regulate by producing and releasing signaling molecules to detect the bacterial concentration. The signaling molecules will bind to receptors on the bacteria and ultimately change the behavior of the bacteria

[66]

.

Metabolites have a variety of functions:

Key factors in a variety of host to microbiota and cell to cell communication

[65]

Metabolite signaling through a series of innate immune receptors affecting host immunity [

65

,

68

], along with regulation of the adaptive immune cell development (T lymphocytes)

[66]

Drive changes in the composition and function of the microbiota through signaling (quorum sensing) [

66

,

68

]

Production of SCFAs, which provide multiple benefits to the host [

45

,

68

]

Participate in various physiological processes, including energy metabolism

[65]

Represent potential biomarkers for early diagnosis of multiple disorders

[65]

Directly kill pathogens by:

disrupting bacterial cell structures.

interfering with bacterial DNA, RNA, and protein metabolism.

resource competition between commensal bacteria and pathogens.

affect cell adhesion and biofilm formation.

regulation of the immune system by activating innate immunity

[66]

Production of vitamins and metabolism of some minerals

[67]

The phrase “metabolome” refers to the biochemical environment derived from the symbiosis of nutrient‐rich milieu provided by the host and the products and metabolites produced by the microbiota [69]. It provides a functional interpretation of cellular activity and physiological status.

The metabolome includes simple amino acids and related amines, lipids, sugars, nucleotides, vitamins, and other intermediary metabolites. The molecules in a metabolome will change depending on the organism being studied and what chemical reactions are occurring in the cell. Metabolomics analyses include sensitive chromatographic methods coupled with mass spectrometry – gas chromatography‐mass spectrometry (GC‐MS) and liquid chromatography‐mass spectrometry (LC‐MS) – as well as nuclear magnetic resonance to identify and quantify compounds in the metabolome [59].

The study of the metabolome is termed metabolomics. This platform includes analytical profiling, quantification, and comparison of metabolites present in biological samples [56, 65].

Metabolomics offers a window into metabolic mechanisms through the use of analytical chemistry and multivariate data analysis [59]. Examples of metabolomics in disease research include certain types of neoplasia with dogs and the use of dogs as a translation model for humans, with the data possibly being bidirectionally beneficial [70, 71].

Due to the complexity of the metabolome, there are two main types of analytic platforms used in metabolomics [56, 59, 71–73]:

Mass spectrometry – achieves a high sensitivity in the analysis. Mass spectrometry may require extensive sample preparation, which can result in the loss of certain compounds. This technique can be limited with respect to the range of metabolite detection per sample and require different preparations of multiple samples to detect maximum number of metabolites. Types of mass spectrometry include:

Gas chromatography‐mass spectrometry (GC‐MS) – oldest tool for qualitative metabolic profiling while providing high chromatographic resolution

Liquid chromatography‐mass spectrometry (LC‐MS) – high sensitivity and provides information regarding metabolite structure.

Capillary electrophoresis‐mass spectrometry (CE‐MS) – high efficiency allowing separation of chemically diverse metabolites in smaller sample volumes with little to no pretreatment required.

Nuclear magnetic resonance (NMR) – quantitative, highly reproducible nondestructive technique. Requires comparatively large sample volumes, but little to no pretreatment of samples, and a range of metabolites can be analyzed in a single sample. Specificity is limited as metabolite resonances may overlap.

These technological advances allow for large quantities of data to be obtained at multiple levels – organelle, cell, tissue/fluid, organ, and entire organism, which provide information on biomolecular functions. Databases for metabolomes and metabolic analyses are available through online platforms:

The Human Metabolome Database –

https://hmdb.ca/

[74]

The Livestock Metabolome Database –

https://lmdb.ca/

[75]

The Bovine Metabolome Database –

https://bovinedb.ca/

[76]

Metaboanalyst –

https://www.metaboanalyst.ca

[77]

1.9.2.1 Metabonomics

A specific branch of metabolomics, termed metabonomics, is dedicated to the study of how the metabolic profile of biological systems change in response to alterations, such as environmental exposures, pathophysiologic events, and nutrition [56, 71, 78]. Thus, this profile is determined by both host genetics and exogenous factors. The term is not always used; however, often the term metabolomics is used to include what could be more strictly defined as metabonomics.

1.9.3 The Proteome and Proteomics

The proteome is the complete set of proteins expressed by an organism [79]. It represents the expression of an organism's genome and actively changes in response to various factors, including the organism's developmental stage, and other internal and external conditions.

“a large‐scale study of protein properties produced by the cell. This includes the expression level, post‐transcriptional modification, and protein interaction, in order to obtain a global view of disease processes or cellular processes at the protein level.” Proteomics aims to catalog the entire protein products of the human genome. Other specific “omics” studies exist, such as lipidomics, which is the study of biological lipids [56].

There are three main strategies of proteomics showing to have an impact:

Protein–protein linkage maps

Genomic DNA sequences of peptide sequences from mass spectrometry

Quantitative protein expression 42.2

Glossary

Biological marker (biomarker) – cellular, biochemical, or molecular alterations that are measurable in biological media such as tissues, cells, or fluids; include biological characteristics that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention

Commensalism – a form of symbiosis where one species lives with, on, or in a host and provides no benefit or detriment to the host

Competition – different species using similarly limited resources in the same ecosystem

Dysbiosis – a change to the composition of resident commensal communities relative to the community found in healthy individuals

Genome – the complete set of DNA (genetic information) in an organism; contains all the information needed to build and maintain that organism throughout its life

Genomics – the study of an organism's genome (genes), including interactions of those genes with each other and the organism's environment

Epigenetics – the study of how behaviors and environment can cause changes that affect the way genes work

Metabolites – small molecular substrates, intermediates, and products of metabolism

Metabolome – the collection of small compound metabolites in an organism

Metabolomics – an analytical profiling technique for measuring and comparing large numbers of metabolites present in biological samples

Metabonomics – the quantitative study of how the metabolic profile of biologic systems change in response to alterations caused by pathophysiologic stimuli, toxic exposures, or dietary changes

Metagenomic – the study of a collection of genetic material (genomes) from a mixed community of organisms

Microbiome – the microbiome is the genetic material of all the microbes – bacteria, fungi, protozoa, and viruses – that live in a particular ecosystem. These microscopic communities can be found in all biological systems, including inside humans and other animals, along with residing in plants, soils, and oceans

Microbiota – the individual bacteria, fungi, virus, and protozoa that make up the microbiome community

Mutualism – both (or all) species benefit in a mutualistic symbiotic relationship

Parasitism – a symbiotic relationship in which one species lives with, on, or in a host species at the expense of the host

Pathogens – a biological agent that causes disease or illness to its host

Prebiotics – food sources that can be utilized by the microbiota and in turn result in a benefit for the host; typically indigestible to the host but rapidly fermented by the host's microbiota

Predation – a symbiotic relationship in which one species hunts, kills, and consumes (an)other species

Probiotics – viable microbes intended to be beneficial to the commensal microbiota

Proteome – the complement of proteins produced by a cell

Proteomics – large‐scale study of proteins produced by a cell; includes the expression level, post‐transcriptional modification, and protein interaction in order to obtain a global view of disease processes or cellular processes at the protein level

Short‐chain fatty acids (SCFAs) – metabolites of microbial fermentation – predominantly acetic acid, butyric acid, and propionic acid

Symbiosis – any relationship or interaction between two dissimilar organisms, with the specific kind of symbiosis depending on whether either or both organisms benefit from the relationship

Symbiotic – a product consisting of a probiotic and prebiotic in combination

References

1

Consorium, T.H.M.P. (2012). Structure, function and diversity of the healthy human microbiome.

Nature

486 (7402): 207–214.

2

Marchesi, J. (2017). What is a microbiome?

https://microbiologysociety.org/blog/what‐is‐a‐microbiome.html

(accessed 11 May 2021).

3

Suchodolski, J. (2016). Diagnosis and interpretation of intestinal dysbiosis in dogs and cats.

The Veterinary Journal

215: 30–37.

4

Ruan, W., Engecik, M., Spinler, J., and Versalovic, J. (2020). Healthy human gastrointestinal microbiome: composition and function after a decade of exploration.

Digestive Diseases and Sciences

65: 695–705.

5

Shahab, M. and Shahab, N. (2022). Coevolution of the human host and gut microbiome: metagenomics of microbiota.

Cureus

14 (6): e26310.

6

Tengeler, A., Kozicz, T., and Kiliaan, A. (2018). Relationship between diet, the gut microbiota, and brain function.

Nutrition Reviews

76 (8): 603–617.

7

Murtaza, N., Cuív, P., and Morrison, M. (2017). Diet and the microbiome.

Gastroenterology Clinics of North America

46: 49–60.

8

Rowland, I., Gibson, G., Heinken, A. et al. (2018). Gut microbiota functions: metabolism of nutrients and other food components.

European Journal of Nutrition

57.

9