Human-Gut Microbiome: Establishment and Interactions

Human-Gut Microbiome: Establishment and Interactions gives an overview of microbiome establishments in humans and basic technologies used to decipher the structure and function of gut microbiome. Other sections focus on the application of microbiomics in different disease manifestations, such as obesity, diabetes, and more. The book provides the basics, as well as mechanistic knowledge underpinning the structural and functional understanding of the microbiome. With the advancement in omics technologies, as well as the development of bioinformatic tools, much research has been undertaken to decipher the microbiomes of different hosts.

This research is generating valuable insights into micro-ecological niches and their impact on humans, hence this new release covers these new insights. The book will be a valuable resource for scientists, researchers, postgraduate and graduate students who are interested in understanding the impact and importance of the omics approach to humans and their microbiomes.

• Provides an overview of the recent developments in meta-omics technologies
• Serves as a unique reference for healthcare professionals, pursuing research on gut homeostasis, and functional foods, as well as nutritional dietary management
• Focuses on the application of microbiomics in different disease manifestations, such as obesity, diabetes, and more

• Language: English
• Publisher: Academic Press
• Release date: Jul 9, 2022
• ISBN: 9780323913713

Book preview

9780323913713_FC

Human-Gut Microbiome

Establishment and Interactions

First Edition

Gunjan Goel

Department of Microbiology, School of Interdisciplinary and Applied Sciences, Central University of Haryana, Mahendergarh, Haryana, India

Teresa Requena

Department of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC), Madrid, Spain

Saurabh Bansal

Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India

Table of Contents

Cover

Title page

Copyright

Contributors

Section A: Human microbiome: Establishment and functions

Chapter 1: An introduction to human gut microbiome

Abstract

Introduction

Human gut microbiota: Structure and composition

Early intestinal microbiota colonization

Gut microbiota and its impact on host health

Gut microbiota and associated diseases

Conclusions

References

Chapter 2: Early colonization of the human gut

Abstract

Establishment and development of intestinal microbiota in early life

Microbiome and reproduction: Is there microbial transmission in utero?

The transfer of bacteria from mother to child

References

Chapter 3: Techniques and challenges in studies related with human gut microbiome

Abstract

Introduction

Early studies of microbiome prior to sequencing

First-generation sequencing

Next-generation sequencing

TGS (single-molecule long read sequencing-SMRT)

Bioinformatics

Advancements in culturing techniques

Multiomics approach in understanding microbe-microbe and host-microbe interaction

Conclusion

References

Chapter 4: Dietary influence on human microbiome

Abstract

Acknowledgments

Introduction

Diet is determinant of the intestinal microbiota composition and function

Food ingredients accessible to the gut microbiota

Mutual interplay of diet, gut microbiota, and health

Food additives and the risk of industrialized microbiota

Concluding remarks

References

Chapter 5: Gut microbiome-derived metabolites in host health and diseases

Abstract

Introduction

Gut microbiome-derived metabolites: The basics

Short-chain fatty acids: Microbial fermentation

Physiological effects of microbial metabolites

SCFAs: Mechanisms of action

SCFAs in gut immune and inflammatory health

SCFAs in cardiometabolic health

SCFAs in cognitive and neurodegenerative health

Newly discovered gut microbial metabolites

Conclusion and prospects

References

Section B: Gut microbiome in health and diseases

Chapter 6: Role of gut microbiome in obesity

Abstract

Introduction

Historical background

Gut microbial diversity

The Firmicutes to Bacteroidetes ratio

The dynamic relationship between obesity and the gut microbiota

Other mechanisms underlying the association between the gut microbiome and obesity

Factors that influence the composition of the gut flora

Modulation of gut flora to treat obesity

Future prospects

References

Chapter 7: Relationship between gut microbiome and diabetes

Abstract

Introduction

Historical background of diabetes and gut microbiome

Gut ecosystem

Type 2 diabetes and gut microbiome

Gestational diabetes and gut microbiome

Type-1 diabetes

Major events that aid the pathogenesis of diabetes during gut dysbiosis

Gut microbiome manipulation for treatment and prevention

Effect of metformin on gut ecosystem

Effect of insulin on gut ecosystem

Future prospects

References

Web Reference

Chapter 8: Human microbiome and neurological disorders

Abstract

Conflicts of interest/competing interests

Introduction

Neuropsychiatric disorder

Neurodegenerative diseases

Autoimmune diseases

References

Chapter 9: Modulation of gut microbiota by probiotic interventions: A potential approach toward alleviating food allergy

Abstract

Introduction

Gut microbiota and its implications in the development of immune system

Gut-dysbiosis and food allergy

Gut microbiota and food allergy

Effect of food allergens on host immune response

Probiotics and their effects in food allergy

Conclusion

References

Chapter 10: Interplay of alpha-synuclein pathology and gut microbiome in Parkinson’s disease

Abstract

Acknowledgments

Introduction

Gut microbiota roles and functions

Pathological implications of gut microbiota dysbiosis

Etiology of Parkinson’s disease and role of alpha-synuclein

Gut microbiota alterations and Parkinson’s disease

Interplay of αSyn and gut microbiota in inducing Parkinson’s disease

Alpha-synuclein in the microbiota-gut-brain axis

Utility of alpha-synuclein and the microbiome for diagnosis and treatment of Parkinson’s disease

Conclusions and perspectives

References

Chapter 11: Impact of indigenous microbiota in gut inflammatory disorders

Abstract

Introduction

Indigenous microbiota shifts the way the host responds to inflammatory triggers in the gut

Dysbiotic microbiota impacts disease outcome in gut inflammatory disorders

Concluding remarks

References

Chapter 12: Emergence of antibiotic resistance in gut microbiota and its effect on human health

Abstract

Introduction

Microbiota in infections

Antimicrobial resistance in gut microbiota

Strategies to prevent resistance generation and spread

Conclusion

References

Chapter 13: The gut microbiome in chronic kidney disease

Abstract

Introduction

Gut dysbiosis in chronic kidney disease

Uremic toxins and the gut microbiome

Inflammation and gut microbiome in CKD: CKD outcomes

Strategies for gut microbiome modulation in chronic kidney disease

Conclusions

References

Chapter 14: Fecal microbiota transfer: Basic and clinical aspects, current applications, and future perspectives

Abstract

Introduction

Donor selection

Sample collection and processing

Recipient preparation

Clinical follow-up and engraftment control

Current indications

Other applications under study

Risks and adverse effects

Cost-effectiveness

Legislation

FMT 2.0

Conclusions

References

Chapter 15: Human gut microbiome and psychological disorders

Abstract

Acknowledgment

Gut microbiome (GM) and physical health

GM and human psychology

References

Further reading

Chapter 16: Effects of contaminants (heavy metals) on the microbiota status in humans

Abstract

Introduction

Human gut microbiota

Modulation of the human gut microbiota

Influence of the human gut microbiota on homeostasis of contaminants

Effects of contaminants (heavy metals) on human gut microbiota

Conclusion

References

Further reading

Index

Copyright

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Contributors

Inês Alencastre     Nephrology & Infectious Diseases R&D Group, INEB—Instituto de Engenharia Biomédica, i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

Uday S. Annapure     Department of Food Engineering and Technology, Institute of Chemical Technology, Mumbai, Maharashtra, India

Ricardo Araujo     Nephrology & Infectious Diseases R&D Group, INEB—Instituto de Engenharia Biomédica, i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

Raquel D.N. Arifa     Department of Microbiology, Instituto de Ciências Biológicas, UFMG, Belo Horizonte, Brazil

Clara Lara Aroco     Faculty of Medicine, University of Castilla La Mancha, Ciudad Real, Spain

Sampan Attri     Viral Testing Facility, Forensic Science Laboratory Punjab, SAS Nagar, Punjab, India

Maria Azevedo

Nephrology & Infectious Diseases R&D Group, INEB—Instituto de Engenharia Biomédica, i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

Aaditi Bagul     Department of Food Engineering and Technology, Institute of Chemical Technology, Mumbai, Maharashtra, India

Saurabh Bansal     Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India

Rafaela R.A. Batista     Department of Microbiology, Instituto de Ciências Biológicas, UFMG, Belo Horizonte, Brazil

Ana Moreno Blanco     Margarita Salas Center for Biological Research (CIB)—CSIC, Madrid, Spain

Camila B. Brito     Department of Microbiology, Instituto de Ciências Biológicas, UFMG, Belo Horizonte, Brazil

Eun-Ha Choi     Plasma Bioscience Research Center, Applied Plasma Medicine Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul, Korea

Miran Čoklo     Centre for Applied Bioanthropology, Institute for Anthropological Research, Zagreb, Croatia

Carolina F.F.A. Costa

Nephrology & Infectious Diseases R&D Group, INEB—Instituto de Engenharia Biomédica, i3S—Instituto de Investigação e Inovação em Saúde

ICBAS—School of Medicine and Biomedical Sciences, Universidade do Porto, Porto, Portugal

Nabendu Debnath     Centre for Molecular Biology, Central University of Jammu, Samba, Jammu and Kashmir (UT), India

Rosa del Campo Moreno

Department of Microbiology, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)

CIBERINFEC, Madrid, Spain

Sunmathi Dhandapani     Department of Community Medicine, Mysore Medical College and Research Institute, Mysore, Karnataka, India

Ivan Dolanc     Centre for Applied Bioanthropology, Institute for Anthropological Research, Zagreb, Croatia

Caio Tavares Fagundes     Department of Microbiology, Instituto de Ciências Biológicas, UFMG, Belo Horizonte, Brazil

Micheli Fagundes     Department of Microbiology, Instituto de Ciências Biológicas, UFMG, Belo Horizonte, Brazil

Sergio García-Fernández     Department of Microbiology, Hospital Universitario Marqués de Valdecilla, Santander, Spain

Gunjan Goel     Department of Microbiology, School of Interdisciplinary and Applied Sciences, Central University of Haryana, Mahendergarh, Haryana, India

Juan Miguel Rodríguez Gómez     Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain

Ihn Han     Plasma Bioscience Research Center, Applied Plasma Medicine Center, Department of Electrical and Biological Physics, Kwangwoon University, Seoul, Korea

Antonija Jonjić     Centre for Applied Bioanthropology, Institute for Anthropological Research, Zagreb, Croatia

Arti Kataria     Kusuma School of Biological Sciences, IIT Delhi, New Delhi, India

Mudassir Azeez Khan     Department of Community Medicine, Mysore Medical College and Research Institute, Mysore, Karnataka, India

Sandra Kraljević Pavelić     Faculty of Health Studies, University of Rijeka, Rijeka, Croatia

Ashwani Kumar     Department of Nutrition Biology, Central University of Haryana, Mahendergarh, Haryana, India

Manoj Kumar     Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India

M. Carmen Martínez-Cuesta     Department of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC), Madrid, Spain

Pawan Kumar Maurya     Department of Biochemistry, Central University of Haryana, Mahendergarh, Haryana, India

Ana Merino-Ribas

Nephrology & Infectious Diseases R&D Group, INEB—Instituto de Engenharia Biomédica, i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

Nephrology Department, Hospital Universitari Doctor Josep Trueta, Girona

Universitat Autònoma de Barcelona, Barcelona, Spain

Ravinder Nagpal     Department of Nutrition and Integrative Physiology, College of Health and Human Sciences, Florida State University, Tallahassee, FL, United States

Pratisha Nair     Department of Food Engineering and Technology, Institute of Chemical Technology, Mumbai, Maharashtra, India

Carmen Peláez     Department of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC), Madrid, Spain

Manuel Pestana

Nephrology & Infectious Diseases R&D Group, INEB—Instituto de Engenharia Biomédica, i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto

Nephrology Department, Centro Hospitalar Universitário de São João

Faculdade de Medicina, Universidade do Porto, Porto, Portugal

Manuel Ponce-Alonso

Department of Microbiology, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)

CIBERINFEC, Madrid, Spain

Teresa Requena     Department of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC), Madrid, Spain

Concepción Rodríguez-Jiménez     Department of Microbiology, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain

Vikas Saini     Biomedical Sciences Program, Department of Vocational Studies and Skill Development, Central University of Haryana, Mahendergarh, Haryana, India

Benedita Sampaio-Maia

Nephrology & Infectious Diseases R&D Group, INEB—Instituto de Engenharia Biomédica, i3S—Instituto de Investigação e Inovação em Saúde

Faculdade de Medicina Dentária, Universidade do Porto, Porto, Portugal

Oluwatoyin Sangokunle     Department of Nutrition and Integrative Physiology, College of Health and Human Sciences, Florida State University, Tallahassee, FL, United States

Ayushi Sharma     Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India

Rahul Shrivastava     Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India

Prashant Singh     Department of Nutrition and Integrative Physiology, College of Health and Human Sciences, Florida State University, Tallahassee, FL, United States

B.M. Snehalatha     Department of Community Medicine, Mysore Medical College and Research Institute, Mysore, Karnataka, India

Beatriz Solo de Zaldívar     Department of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC), Madrid, Spain

Daniele G. Souza     Department of Microbiology, Instituto de Ciências Biológicas, UFMG, Belo Horizonte, Brazil

Ankit Srivastava     Kusuma School of Biological Sciences, IIT Delhi, New Delhi, India

Anamika Verma     Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India

Ashok Kumar Yadav     Centre for Molecular Biology, Central University of Jammu, Samba, Jammu and Kashmir (UT), India

Dharmendra Kumar Yadav     College of Pharmacy, Gachon University of Medicine and Science, Incheon City, Korea

Section A

Human microbiome: Establishment and functions

Chapter 1: An introduction to human gut microbiome

Sampan Attria; Saurabh Bansalb; Gunjan Goelc    a Viral Testing Facility, Forensic Science Laboratory Punjab, SAS Nagar, Punjab, India

b Department of Biotechnology and Bioinformatics, Jaypee University of Information Technology, Waknaghat, Solan, Himachal Pradesh, India

c Department of Microbiology, School of Interdisciplinary and Applied Sciences, Central University of Haryana, Mahendergarh, Haryana, India

Abstract

The human gut microbiome has been a dominant research area over the past two decades, whereby the role of gut microbes in maintaining the overall homeostasis in an individual has been emphasized. The major target of gut microbiome studies is to establish the role of this microbial niche in intestinal inflammatory diseases, metabolic disorders, cancer and neurodegenerative diseases, among others. The present chapter discusses the current knowledge on early colonization of gut, its establishment, and functions of gut microbiota in maintaining an individual’s health. Although a plethora of research has been conducted on these aspects, further studies are still warranted to have a detailed mechanistic understanding of host-microbe interaction individually or as community-based studies. The studies should include analysis of omics data along with host physiology and environmental factors to identify the potential microbial biomarkers behind their beneficial effects.

Keywords

Gut microbiome; Infant; Colonization; Factors; Dysbiosis

Introduction

The human microbiome or microbiota refers to the microbes living in symbiotic relationships in our body. The human gastrointestinal (GI) tract houses approximately 10¹³–¹⁴ microorganisms (predominately bacteria), collectively called gut microbiota. The number of microbes inhabiting the GI tract is estimated to be around in equal proportion as of human cells [1] and over 100 times the amount of genomic content as compared to the whole human genome. Due to the enormous number of small microbial communities in the GI tract, the gut microbiota is often referred to as a superorganism. It can be viewed as a hidden metabolic organ that significantly effects the host metabolism, physiology, nutrition, and immune function. As the gut microbiota is involved in different metabolic activities of an individual, therefore, the gut microbiome is also known as the second brain with a composite enteric nervous system that communicates with the brain via the vagus nerve [2,3]. In general, the predominant phyla in the gut region are Firmicutes, Bacteroidetes, and Actinobacteria. However, with the new developments of genetic, bioinformatic tools, and metagenomic techniques, the structure and functions of microbiomes in community based or clinical studies have been revolutionized. The omic technologies such as metagenomics, including 16S ribosomal RNA (rRNA) gene sequencing, metagenomic assembly, whole genome shotgun (WGS) metagenomic sequencing, reference genome mapping, gene cataloging, and metabolic reconstruction, along with transcriptomics, proteomics, metatranscriptomics, metabolomics, and culturomics have helped us in establishing the role of an individual’s microbiome under healthy and diseased state. The sequence-based microbiome projects such as the Human Microbiome Project (HMP) and Metagenomics of the Human Intestinal Tract (MetaHIT) consortium established the fundamental as well as the advanced role of the microbiome in health and diseased states [4].

Moreover, the development of the humanized gnotobiotic animal model serves as a tool to determine the effect of diet, environment, and other host factors in the establishment and role of microbiota in the intestine [5]. Recent data have indicated an increasing trend in research on microbiome studies with a peak during 2016 and 2017. The recent research clearly determines the significance of the human microbiome, which is still at its preliminary phase; however, the literature suggested the promising role of microbiome studies in establishing the information gap in microbiome-host associations and their role in disease pathogenesis, as well as therapeutic significance. The present chapter provides an overview of the structure and function of human gut microbiota and their role in shaping an individual’s health. The linkage of gut dysbiosis under different clinical manifestations has also been discussed.

Human gut microbiota: Structure and composition

The gut microbiota is highly diverse compared to the microbial communities present in some other body parts and displays a high degree of functional redundancy. Till now approx. 2100 species have been isolated from human body, which are further classified into 12 different phyla, of which more than 90% belongs to Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. Among these four major phyla, the healthy human gut is dominated by the phyla Firmicutes and Bacteroidetes. The host with a high microbial gene count had a more robust microbiota and lower risk of metabolism-related disorders than those with a low gene count. The high gene count microbiota included Fecalibacterium sp., Akkermansia sp., Anaerotruncus colihominis, and Butyrivibrio crossotus. On the other side low gene count microbial community included Staphylococcus, Campylobacter, Anaerostipes sp., Parabacteroides, Dialister, and Porphyromonas. Also, individuals with low gene count microbial communities lack metabolic system for the degradation of aromatic amino acids, nitrite reduction, and β-glucuronide. All these compounds led to damage to DNA and possess potential for carcinogenic effects.

Each compartment of the digestive tract possesses diverse microbial population and functions due to changes in environmental conditions in each compartment. The major environmental conditions include acidic nature of gastric juices, presence of bile salts, pancreatic enzymes, presence of mucous layer or pathogenic microorganisms, etc., that determine richness, diversity, and population of the microbial community. As one travels from the oral cavity to the colonic region, there is a significant difference in concentration and diversity of microbial communities ranging from 10² per gram of contents in the stomach to 10¹⁴ per gram of contents in the colonic region [6,7] (Fig. 1).

Fig. 1

Fig. 1 Major microbial groups present at each phase of the digestive tract. Adapted from Ruan W, Engevik MA, Spinler JK, Versalovic J. Healthy human gastrointestinal microbiome: composition and function after a decade of exploration. Dig Dis Sci 2020;65(3):695–705.

Oral cavity

The oral cavity makes up several natural microbial habitats such as tonsils, teeth, gums, and tongue. It is the second largest and diverse microbial niche after the gut, with an estimated over ~   700 species of bacteria and also harbors viruses, fungi, and protozoa. The oral cavity serves as an opening door to the food that further moves toward the GI tract. In oral cavity, the initial digestion of food takes place with the help of salivary enzymes. Six major phyla that comprise 96% of the taxa in the oral cavity include Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, Spirochaetes, and Fusobacteria. At the genera levels, Streptococcus has been reported as a dominant bacterial group in different sites of the oral cavity, followed by Haemophilus, Neisseria, Actinomyces, and Prevotella. The major viral groups of bacteriophages belonging to the Caudovirales order, including Myoviridae, Siphoviridae, and Podoviridae families are also reported. Candida is the commonly encountered eukaryotic genus among the 85 genera of fungi reported in the oral cavity. The factors that govern the establishment of the oral cavity by different microbial groups include differences in surface structure at the micro-scale, functionality and shedding of those surfaces, as well as nutrient flow and oxygen level [8].

Esophagus

After a small transit time of food in oral cavity, it is further transferred down to the stomach through the esophagus. The esophageal mucosa is one of the prominent sites colonized by microbial groups; therefore, understanding the possible role of microbial alterations in the esophageal lining is helpful in determining the outcome of esophagal diseases. The healthy esophageal microbiome is reported to be similar in composition to the oral microbiome; however, not all oral bacteria are apparently able to colonize the esophageal mucosa. The bacterial population in the normal distal esophagus is composed of approximately 6 phyla and 140 species. The esophagus is colonized majorly by Firmicutes followed by members of phyla Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and TM7. The most abundant bacterial communities in the esophagus belong to Prevotella (Prevotella melaninogenica and Prevotell apallens), Rothia (Rothia mucilaginosa), Streptococcus (Streptococcus mitis/oralis/pneumoniae), Haemophilus (Haemophilus parainfluenzae), and Veillonella. Similar to the oral cavity, the diversity of microbial groups in the esophagus is also influenced by diet and other environmental factors [9].

Stomach

The stomach is one of the major digestive organs of the human body. For digestion, gastric acid and proteolytic enzymes that process the ingested food are released into the stomach. Due to its very low pH environment, the growth of many microbes is suppressed. These harsh conditions provide defensive system against many pathogens. Despite the fact of acidic conditions and other unfavorable conditions, few but diverse microbial communities are found in the stomach. This region has a lesser number of microbes (∼   10²–10³ colony-forming units (CFU)/mL) as compared to the other regions of the GI tract. The major phyla reported in the gastric region include Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Actinobacteria; and at the genus level, Bacillus, Enterobacter, Streptococcus, Leptotrichia, Pseudomonas, Veillonella, Haemophilus, Rothia, and Helicobacter[6,10].

Small intestine

The small intestine consists of the duodenum, jejunum, and the ileum and is the site where most of the nutrients are digested and absorbed. This compartment also provides an unfavorable environment for microbial proliferation due to the short transit time of food and the presence of digestive enzymes and bile acids, resulting in lower and less diverse microbial biomass. Bile acids are bactericidal to certain groups of bacteria due to their surfactant property and are known to configure the composition and diversity of the microbiome, especially in the small intestine. The shorter transit time of the food in the small intestine alters adherence and persistent colonization characteristics of microbial groups. Among the different portions of the small intestine, the duodenum contains approximately 10²–⁴ CFU/mL, jejunum contains 10⁴–⁷ CFU/mL, and ileum has an estimated microbial concentration of 10³–⁸ CFU/mL. Firmicutes dominate the small intestinal microbiota, also including Proteobacteria, Actinobacteria, and Bacteroidetes, which are primarily facultative and obligate anaerobes. The common bacterial genera dominant in the small intestine includes Lactobacillus, Veillonella, Staphylococcus, Clostridium, Escherichia, Streptococcus, and Bacteroides[11,12].

The colon

The colon is divided into four main sections: ascending, transverse, descending, and rectum. It is the site of water and mineral absorption, as well as the fermentation of complex undigested nutrients. The healthy human colonic region contains a relatively highly diverse concentration of microbiota. The colonic microbiota accounts for more than 70% of all microbes found in the body. Because of its unique composition, diversity, and functional qualities, the colon microbiota resembles a fingerprint. Although the length of the colon region is shorter than the small intestine, the transit time in this region is considerably longer (>   30 h), which favors the adherence and colonization by different microbial groups in this region. Among the different regions of the colon, the proximal and cecum region is the major site of fermentation in the gut, and the distal colon mainly absorbs potential useful fluids and electrolyte salts [13]. The predominant colon bacteria phyla present in the healthy human are Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Verrucomicrobia. In healthy humans, the dominant phyla Firmicutes accounts for 90% of the total population. The major genera included in this phylum are butyrate-producing Gram-positive microorganisms (Ruminococcus, Clostridium, Eubacterium, Butyrivibrio, Anaerostipes, Roseburia, Faecalibacterium, etc.) and Bacteroidetes (Bacteroides, Porphyromonas, Prevotella, etc.). The other phyla include Proteobacteria (members like Escherichia and Enterobacteriaceae), Actinobacteria (Bifidobacterium), Fusobacteria, and Verrucomicrobia (such as Akkermansia) species. The loose outer colonic mucus layer plays a vital role in the colonization of microbes in that region. The metabolic activity of colonic bacteria results in the production of short-chain fatty acids (SCFA). The three most abundant SCFA present in feces are acetic acid, propionic acid, and butyric acid (3:1:1–10:2:1). Among these SCFA, butyric acid is the most significant SCFA for human health as it acts as key energy source for colonocytes, anticarcinogenic properties, and activation of intestinal gluconeogenesis. Propionic acid is also an energy source that plays a role in gluconeogenesis when transferred to the liver. Acetic acid is the most abundant SCFA and is an essential metabolite/cofactor for the growth of other microbes. Any alterations in the composition and structure of colonic microbiota have been associated with emergence of gut-dysbiosis-related diseases such as inflammatory bowel diseases, celiac disorders, and other diseases [14–16].

Early intestinal microbiota colonization

Initially, the GI tract was considered as sterile at birth, but recent findings have revealed the presence of bacteria in the fetal gut before birth. The presence of bacteria in the placenta, umbilical cord blood, amniotic fluid, and meconium of healthy newborns suggests that microbial colonization starts in fetal life; however, direct evidence of in utero transfer of bacteria in humans is lacking [17]. Early microbial colonization plays a crucial role in the healthy immunological and metabolic development. Rapid colonization of the gut begins within the first few days after birth that further leads to the stabilization in the following days/months. The factors that control and shape the development of the gut microbiota are categorized into intrinsic factors (such as the host genetics, bacterial mucosal interactions and receptors, peristalsis, colonic pH and secretions, and immunogenic responses) and extrinsic factors (mode of delivery, geographical region, mode of feeding maternal and surrounding microbes, hygiene practices, and drug/antibiotic therapy). The early colonizers include Proteobacteria (e.g., Escherichia or Shigella) at birth. After several days from birth, members of the phylum Actinobacteria (e.g., Bifidobacterium) are reported to increase, which might be due to breast feeding [18]. Further, abundant levels of Enterobacteriaceae, Bifidobacteriaceae, and Clostridiaceae are reported at the age of 2 months, with a consistent decrease by the age of 18 months. Therefore, from infancy to the elderly, an increase in Firmicutes bacteria with a decrease in Bacteroidetes is observed [19].

Prenatal phase

Host genetics

Scientific evidences have provided linking the host genetics and gut microbial composition. The studies in twins and families have highlighted the contribution of host genetics in gut microbial composition with a heritability estimate of 1.9%–8.1%. The genome-wide association studies identified several microbial quantitative trait loci and also indicated the relationship between host genetic factors and microbial communities colonizing the gut. The studies have shown a correlation between gut microbiota and host genotype in infants and found that the fecal microbes of monozygotic twin siblings were more similar as compared to dizygotic twin siblings. Goodrich et al. [20] have reported that many bacterial taxa were influenced by host genetics, with the family Christensenellaceae in the phylum Firmicutes being the most heritable taxon. Christensenellaceae is also linked with the fucosyltransferase-2 gene, which encodes an enzyme responsible for ABO blood group antigen expressed on the intestinal surface. The members of Christensenellaceae may also interact with host genetics to affect the risk of colon cancer. However, inconsistency in the studies relating genetics with gut microbial composition is challenging due to different sample sizes, usage of different metagenomic tools, and other heterogeneity in the studies.

Intrauterine exposure

The presence of several microbial species and DNA in placenta, amniotic fluid, umbilical cord blood, foetal membranes, and meconium of healthy pregnant women suggests that gut colonization may begin prenatally. However, the mechanism of transfer of microbes from these to new born is still unclear. Few studies have highlighted the role of dendritic cells in Peyer patches in transfer of microbes from the maternal gut lumen and further to enter the lymphatic and blood circulation. Once in circulation, the bacteria may be transferred to the fetus across the placental barrier and lead to early colonization of intestine of fetus. The presence of bacteria in meconium supports the theory of microbiota colonization prior to birth. Study by Collado et al. [21] reported the presence of microorganisms in the amniotic fluid and placenta at the time of cesarean delivery. However, the mechanisms by which they pass through the maternal-fetal interface are not very well understood. Also, in the women who have undergone cesarean delivery, Lactobacillus signatures, described as delivery-associated signals, have been reported to present in higher frequency in the placenta of women with vaginal delivery or during labor before delivery.

Exposure to antibiotics

The administration of antibiotics during pre, peri, and postnatal periods negatively affects the neonatal gut microbiota. The Beta-Lactams antibiotics are generally administered prophylactically to prevent neonatal Group B streptococcal infection and maternal morbidity after cesarean section. Two different mechanisms of the effect of antibiotics on early microbial composition have been suggested. The antibiotics reach the bloodstream of neonates with a residence time of up to 10 h and influence the microbial composition. Also, these antibiotics may disturb the maternal vaginal and gut microbiota and consequently could alter the vertical microbial transmission process and postnatal infant immunity. In general, mother’s exposure to antibiotics leads to relatively higher concentration of Proteobacteria with a concurrent decrease in Actinobacteria and Bacteroidetes during the first 10 days. However, this effect was reported to decline after 30 and 90 days. The administration of antibiotics is reported to lower the number of commensal bacteria with delayed colonization with Bifidobacterium and Bacteroidetes and concurrent increase in potential pathogens [22,23].

Maternal weight and stress

Maternal obesity leads to microbial changes in maternal and infant fecal microbiota, including an increase in Firmicutes, Bacteroidetes, and the Actinobacteria phyla and decrease in Bifidobacterium. However, the results obtained in most of the studies are inconclusive due to inconsistencies in uniform taxonomic data obtained in the studies. Excessive weight gain during pregnancy has been associated with a lower abundance of the Prevotella/Bacteroides group and a higher proportion of the Clostridium histolyticum group [24]. Also, the mothers with a high rate of stress level during pregnancy had a relatively higher concentration of Proteobacteria and lower levels of Lactobacillus and Actinobacteria. Along with weight, stress during the first few weeks of pregnancy is also reported to induce a change in the maternal gut microbiota shape and structure, especially during period of pregnancy when microbial community structure is most variable with the gestation period. In addition to maternal gut microbiota, stress also induces alteration in vaginal microbiome, which may result in perturbations in maternal gut microbiota composition and function. Overall, this alteration in microbial communities and microbe-derived metabolites and substrates also affect the infant gut’s colonization. The transmission of stress altered vaginal microbiome may also disrupt microbe-neonate interactions necessary for regular neurological development, immune system modulations, and other metabolic activities in infants [25].

Postnatal phase

Mode of delivery

Mode of delivery is one of the major factors that define the shape of colonization of microbiota in infants. Fecal microbial composition of vaginally delivered neonates is more similar to that of vaginal microbiome of the mother, with Lactobacillus, Prevotella, and Atopobium being predominating. In comparison, the fecal microbial composition of cesarean delivered neonates was more similar to the maternal skin and the hospital environment with an abundance of Propionibacterium, E. coli, Staphylococcus, Corynebacterium, Klebsiella pneumonia, and other potential pathogenic bacteria. Also, many reports suggest the absence of Bifidobacterium in the stool sample of cesarean delivery infants compared to vaginally delivered infants. Data from investigations revealed that cesarean delivery infants had been associated with long-term effects such as allergies, celiac diseases, asthma, obesity, and autoimmune diseases such as type 1 diabetes. The microbial profile remains distinct depending on delivery time. A full-term delivery is characterized by Parabacteroides, Bacteroides, and Christensenellaceae by successive years one, two, and four, respectively, whereas preterm deliveries are characterized by Lactobacillus, Streptococcus, and Carnobacterium at years one, two, and four, respectively [26]. The differences in the establishment of infant gut microbiota composition may be in both the source of the microbial community and the infant’s environment. In C-section delivered infants, the disappearance of Bacteroides species in the second week after birth is reported due to lack of a supporting factor, presence of antagonist factors, or differences in the fitness of colonizing strains [27].

Gestational age

The duration of gestation phase is another critical aspect that shapes the infant intestinal microbial colonization. The microbial composition of preterm infants is also different from the full-term infants as the preterm infants have less bacterial diversity and delayed colonization, mainly by Lactobacillus and Bifidobacterium as compared with infants born after a full-term pregnancy. Early colonizers in preterm infants are potentially pathogenic microbes, such as Staphylococcus, Klebsiella, E. coli, Enterococcus, and Streptococcus. In addition to this, the extensive intake of antibiotics and other drugs in preterm infants can disturb the diversity of gut microbiota that may further lead to GI disorders such as necrotizing enterocolitis [28].

Mode of feeding

The mode of feeding is one of the most important factors for gut microbiota shaping and infant gut microbial diversity. Many studies have reported differences in bacterial composition between breast-fed and formula-fed infants. Differences in microbial composition can be attributed to the presence of bacteria such as Staphylococcus, Streptococcus, Propionibacterium, Bacteroides, Faecalibacterium, Roseburia, Lactobacillus, and Bifidobacterium in the breast milk, which may act as probiotics. In addition, human milk also contains large quantities of structurally diverse oligosaccharides (human milk oligosaccharides, HMO) with prebiotic activities, whereby these substrates are fermented by gut bacteria such as Lactobacillus, Bifidobacterium, and Bacteroides for further proliferation in the intestine [29].

Gut microbiota and its impact on host health

Imbalance or disturbance in the composition of gut microbial community can lead to dysbiosis. This imbalance in gut microbial populations or diversity results in immune-mediated diseases, such as necrotizing enterocolitis, irritable bowel syndrome/disease, and extra intestinal diseases such as asthma and atopy. Moreover, based on well-documented studies, a significant role of gut microbiota in overall host health has been established via gut-brain bidirectional axis. Within the gut, the microbial communities establish a symbiotic relationship with the intestinal mucosa and impart nutrient metabolism, gut protective functions, and immunological modulations in the healthy individual (Fig. 2).

Fig. 2

Fig. 2 Possible health benefits of healthy gut microbiota.

The gut microbiota mainly derives its nutrients from dietary polysaccharides and undigested nutrients. The nutrients and dietary components that have escaped small intestinal digestion and absorption are fermented by colonic microbes such as Fecalibacterium, Bacteroides, Bifidobacterium, and Roseburia, among others. These fermentations result in the release of metabolites that are highly beneficial and act as a source of energy for the host. SCFA such as acetic acid, propionic acid, and butyric acid are produced due to the fermentation of indigestible dietary fibers in the colonic region by the microbiota. These fatty acids are absorbed through the gut epithelium tissues and further play an important role in various physiological processes in the host body and are metabolized by the liver. Butyrate or butyric acid usually acts as a major source of energy for colonocytes. They also play an important antiinflammatory role and affect other metabolic pathways such as gluconeogenesis and lipid metabolism. The established microbiome is also reported in the synthesis of vitamin K and constituents of the B group vitamin (vitamin B2, vitamin B9, and vitamin B12) [30]. Metabolism of xenobiotics is one of the metabolic activities of gut microbiota. The microbial communities may change the pharmacokinetics of pharma drugs, toxicants, and heavy metals via different mechanisms. These actions are suggested via direct chemical modification/transformation of xenobiotics, limiting the absorption of xenobiotics in the GI tract by increasing the expression of cell to cell adhesion proteins and strengthening the protective mucosal layer. However, the role of host gene expression such as multidrug resistance proteins (CYP450s), regulated by the gut microbiome, is another possible way of detoxifying xenobiotics [31].

This diverse microbial colonic ecosystem also plays a crucial role in the prevention of infectious diseases. Certain gut microbial strains can produce and secrete bacteriostatic or bactericidal molecules, such as bacteriocins or microcins. Another mechanism by which the gut microbiome inhibits intestinal colonization by pathogens is through nutrient competition. Facultative anaerobic gut microbial bacteria such as Lactobacillus lower the colonic region’s oxygen concentrations, making a less favorable environment for pathogens. Also, some metabolites such as organic acids and SCFA produced by gut microbiota can have an inhibitory effect on pathogens (Fig. 3).

Fig. 3

Fig. 3 Mechanisms of action of gut microbiota. Adapted from Khalighi A, Behdani R, Kouhestani S. Probiotics: a comprehensive review of their classification, mode of action and role in human nutrition. In: Probiotics and Prebiotics in Human Nutrition and Health. IntechOpen; 2016. vol 10. 63646.

The gut microbiota contributes to gut immunomodulation of both the innate and adaptive immune systems. Several gut microbial communities alter the intestinal immune system by producing secreted metabolites and factors that influence the development and functionality of intestinal epithelial and immune cells. The cells and components of immune system that contribute in the immunomodulatory process include the gut-associated lymphoid cells, IgA-producing B cells, regulatory and effector T cells, Group-3 innate lymphoid cells, and macrophages dendritic cells in the lamina propria.

Gut microbiota and associated diseases

The gut microbiome is established from early life to adulthood when it achieves stability of its community to perform its functions in a healthy state, maintaining the gut homeostasis. Any disruption in this homeostatic stage is referred to as dysbiosis. Dysbiosis can negatively affect the typical colonic environment, immune cells maturation processes, and enhanced susceptibility of the host toward pathogenic microbes. Gut dysbiosis has been associated with numerous diseases related to metabolic disorders, such as diabetes, obesity, and cardiovascular disease, inflammatory bowel disease, neurological disorders, and others. The literature is inconclusive about dysbiosis, which could be a result of a disease or may cause disease. The specific role of the gut microbiota in the onset of different diseases is discussed in different chapters of the book. The investigation of the role of the gut microbiota in these diseases will help in determining the fecal therapy to modulate the community from a dysbiotic state into a healthy homeostatic one [32] (Fig. 4).

Fig. 4

Fig. 4 Common disorders due to gut dysbiosis.

Conclusions

A significant advancement in sequencing technologies has enabled us to determine the interaction between the host and its gut microbial community, which is a bidirectional relationship. The progress in this area helps us to understand the factors that govern the establishment of microbiota in an infant and further which factors may influence the proliferation of specific microbial groups during the growth. However, the data reported worldwide are inconsistent and remain inconclusive in many aspects due to variability in the studies regarding subjects and methods of analysis. Therefore, the use of standardized methods and collaboration is imperative to determine the core microbial composition at an early stage of life and understand the role of the gut microbiota in host health development. These collective efforts will lead to develop disease-specific microbial biomarkers that can be used potentially for diagnostics and eventually to design treatment for personalized medicine.

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Chapter 2: Early colonization of the human gut

Juan Miguel Rodríguez Gómez    Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain

Abstract

The acquisition and establishment of the gut microbiota is a process with short- and long-term consequences for the health of the host. This process is influenced by many host, microbial, environmental, and medical factors. Some studies have suggested that the acquisition of the human microbiota may begin in the maternal uterus. However, while it is possible that not all healthy babies are born sterile as previously assumed, it is also true that studies supporting the in utero colonization hypothesis should be viewed with caution as most of them contain relevant methodological limitations. From a microbial perspective, a newborn represents an essentially uninhabited island, where the first settlers are given a priority settlement option, thus creating opportunities or restrictions for the next group of settlers. For this reason, the influence of vertical mother-to-infant transfer of microbes during the perinatal and neonatal period seems particularly relevant.

Keywords

Microbiota; Microbiome; Colonization; Gut; Neonate; Infant; Human milk; Prematurity

Establishment and development of intestinal microbiota in early life

The establishment of the gut microbiota is a particularly important process for the health of the host [1]. Alterations in the composition of the gut microbiota during neonatal life and during childhood have been associated with pediatric disorders and with various diseases during adult life. This notion explains the need for a thorough understanding of the composition and development of the infant microbiota, the interactions of members of the microbiota with each other and with host, and the mechanisms by which these interactions are relevant for health throughout life.

Factors affecting microbial colonization of the neonatal gut

Although the potential existence of a prenatal gut colonization remains as a controversial issue (and this issue will be discussed later), colonization of the neonatal gut actually represents the de