Microbiome and Human Health: Recent Insights and Future Directions

Azza Moustafa Fahmy
Theodore Bilharz Research Institute, Giza, Egypt
Correspondence to: hageradel23@yahoo.com

DOI: https://doi.org/10.70389/PJPH.100002

Additional information

• Ethical approval: N/a
• Consent: N/a
• Funding: No industry funding
• Conflicts of interest: N/a
• Author contribution: Azza Moustafa Fahmy – Conceptualization, Writing – original draft, review and editing
• Guarantor: Azza Moustafa Fahmy
• Provenance and peer-review:
  Commissioned and externally peer-reviewed
• Data availability statement: N/a

Keywords: Microbiome, Microbiota, Probiotics, Human health, Dysbiosis, Immune modulation, Molecular biology, fecal microbiota transplantation.

Peer-review
Received: 3 August 2024
Revised: 4 September 2024
Accepted: 13 September 2024
Published: 11 October 2024

Introduction

The human microbiome is the collective genome of microorganisms found within and on the human body.¹ This complex ecosystem, which includes bacteria, archaea, viruses, and fungi, colonizes many bodily regions, including the skin, mucosa, gastrointestinal tract, respiratory tract, urogenital tract, and mammary gland.² The gut microbiome is the most densely inhabited of these and has been the primary subject of investigation due to its tremendous impact on host physiology and health.

The human microbiome is important for maintaining health since it influences metabolic and immunological activities.³ It fluctuates in response to factors such as age, nutrition, lifestyle, hormonal changes, hereditary genes, and underlying disorders. Dysbiosis, or changes in the microbiota, can cause serious illnesses such as cancer, cardiovascular disease, inflammatory bowel disease (IBD), and antibiotic-resistant infections.^4,5 Understanding the host–microbe interactions is critical for detecting and treating these disorders.

Recent developments in sequencing technologies and bioinformatics have transfigured our thought of microbial communities, exposing their complex interactions with the host. These studies have found that nutrition, genetics, age, and environmental exposures all have an impact on the microbiome’s composition. Furthermore, dysbiosis has been linked to a variety of diseases, including IBD, obesity, diabetes, and mental health disorders.

Traditional culture-based approaches for researching microorganisms sometimes fail to recreate natural microbial environments, limiting the detection of unidentified microbial species in the human microbiome.⁶ Metagenomics, combined with next-generation sequencing (NGS), has substantially increased our understanding by permitting us to examine entire ecosystems in their natural environments.⁷ Projects such as the Human Microbiome Project (HMP) and the American Gut Project have greatly expanded our understanding of microbiome composition and function, which is critical for considering host–microbiome interactions and their role in disease development.

The human microbiome is a dynamic and adaptive component of our biology, performing critical roles that the human genome alone cannot achieve.⁸ The study of the microbiome improves our understanding of basic human biology and opens up new pathways for therapeutic approaches that target the microbiome to prevent or treat disease.⁹ As research advances, the ability to modify the microbiome for health advantages grows more promising, emphasizing the relevance of this topic in future biomedical research and clinical practice.¹⁰

Historical View: Early Discoveries and Foundational Studies

From the late nineteenth century to the present, research on the human microbiome has advanced dramatically. Antonie van Leeuwenhoek used a microscope to investigate microbial diversity in the 1680s, but he made no connection between these bacteria and health.¹¹ In the early 1900s, Élie Metchnikoff proposed that ingesting lactic acid bacteria could benefit health, laying the framework for future probiotic research.¹²

Louis Pasteur and Robert Koch made significant advances in the late nineteenth century by developing methods for examining germs, which led to the identification of bacteria as the cause of diseases such as anthrax, tuberculosis, and cholera. The advent of DNA sequencing technology, particularly 16S rRNA gene sequencing in the 1970s, transformed microbial identification and categorization, allowing scientists to investigate microbial diversity in the human body with higher precision.¹³

The National Institutes of Health initiated the HMP in 2007 to characterize microbial communities across diverse body sites and investigate their roles in health and illness.¹⁴ This investigation demonstrated the variety and complexity of the microbiome, as well as the considerable variation in microbial communities between individuals and body regions due to diet, lifestyle, and genetics.

Research has changed from just cataloging microbial species to comprehending their functional importance. Advances in metagenomics and sequencing technologies have demonstrated that the microbiome has a substantial impact on health, notably in terms of metabolism and obesity risk. The microbiome can influence energy extraction from meals and modulate genes involved in energy storage, indicating its potential as a therapeutic target.¹⁵

This review will describe current advances in microbiome research and investigate the therapeutic potential of microbiome modification. It solves significant research problems, such as interindividual variability and ethical considerations. The review is important to the scientific and medical communities because it improves understanding of the microbiome’s involvement in health and disease, supports the development of customized medicines, and informs public health efforts. It stresses the integration of multi-omics data and identifies future research prospects.

The Human Microbiome: Composition and Functions

The human microbiome is a diverse and dynamic collection of microorganisms, including bacteria, archaea, viruses, and fungi, that live in a variety of anatomical places including the gut, skin, mouth cavity, and respiratory system. These microbial communities play an important role in human health by regulating a variety of physiological systems. The composition and function of the microbiome varied greatly between bodily regions, with each containing distinct microbial communities suited to their specialized environments.

Composition of the Human Microbiome

The human body is colonized by a wide range of microbial populations that differ dramatically across organ systems and across time, impacted by lifestyle and health conditions.¹⁶ The composition and density of these microbiomes vary according to body site (Figure 1). For example, the upper respiratory tract has a higher population density than the lower parts. The stomach has lower microbial densities than the jejunum, cecum, and colon.¹⁷ Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria are the most common bacterial phyla in the human microbiome, with composition altering according to body habitat.^18,19

Microbial Diversity of Microorganisms in Different Body Sites

The human body is home to a diverse range of microorganisms that live in a variety of anatomical places, each with its microbial community tailored to its environment. This microbial diversity is essential for sustaining homeostasis and health because different bacterial species contribute distinct tasks based on their location.

• Gut Microbiome: The gut microbiome is the most diverse and densely populated microbial community in the human body.²⁰ It has over 3 million genes, greatly exceeding the 23,000 genes in the human genome.²¹ The gut microbiota acts as a “superorganism” alongside the host, playing critical roles in digestion, nutrition absorption, and immune protection. They help metabolize bile acids, lipids, amino acids, vitamins, and short-chain fatty acids (SCFAs) while also preventing pathogenic colonization through gut integrity and competitive exclusion of dangerous microorganisms. Despite changes in microbial composition, the gut microbiota’s essential functions remain consistent among individuals.²²
• Skin Microbiome: The density and number of glands and hair follicles on the skin offer unique microenvironments for microbial growth.²³ These changes influence the quantity and composition of microbial communities on the skin.²⁴ Skin microbiota suppresses pathogens by creating bacteriocins, proteases, phenol-soluble modulins, and fermentation byproducts. They also create anti-virulence chemicals, which limit viruses’ capacity to adhere to and enter tissues. Furthermore, skin microorganisms can detect environmental signals and regulate their gene expression in response, impacting pathogen virulence genes. While much study has focused on competitive interactions between skin microorganisms, they also cooperate by exploiting each other’s metabolic products.²⁵
• Oral Microbiome: The mouth cavity contains a diverse microbiome of bacteria, archaea, viruses, and fungi.²⁶ These microorganisms live in specific areas of the oral cavity, including the tongue, hard palate, tooth surfaces, and gingival fissures. The oral microbiome is important for maintaining oral health because it helps produce biofilms (dental plaque) and prevents pathogen colonization.²⁷ However, abnormalities in the oral microbiota can cause dental caries, periodontal disease, and other oral infections.²⁸
• Respiratory Tract Microbiome: The respiratory tract microbiota differs between upper and lower respiratory tracts. The respiratory microbiome contributes to respiratory health by interacting with the host immune system, boosting protective responses, and preventing pathogenic colonization through antimicrobial production. This relationship promotes lung homeostasis by maintaining constant communication among bacteria, epithelial cells, and immune cells. The lung microbiota is regarded as a “mirror of lung health status,” with considerable changes in composition occurring during respiratory illnesses.²⁹
• Urogenital Microbiome: Men and women have distinct urogenital microbiomes due to differences in anatomy and hormones.² Lactobacillus species dominate the vaginal microbiome in women, producing lactic acid and contributing to a low pH that protects against infections.³⁰ The male urogenital tract microbiome is less well understood; however, it contains bacteria such as Corynebacterium and Staphylococcus species.³¹

Factors Prompting Microbial Diversity

Several variables influence microbial diversity in these bodily areas, including diet, age, genetics, environmental exposures, and lifestyle choices. Antibiotics, for example, can alter microbial populations and cause dysbiosis, which has been linked to a variety of health issues.³² Role in Health: Functions of the Microbiome in Digestion, Immune Modulation, and Disease Prevention

The human microbiome plays an important role in maintaining health by participating in a variety of physiological processes. This complex population of bacteria makes an important contribution to digestion, immune system regulation, and disease prevention. The relationship between the host and its microbiota is a critical factor in health and disease, impacting both metabolic and immunological functions.

• Digestion and Metabolism: The microbiome plays a crucial role in digestion and metabolism, particularly in the gut. It ferments dietary fibers and complex carbohydrates that humans cannot digest, producing beneficial metabolites like SCFAs. These SCFAs are crucial energy sources for the host and promote intestinal health.³³ Butyrate, in particular, is the principal energy source for colonocytes and contains anti-inflammatory qualities, which help the intestinal barrier function and reduce the risk of inflammatory illnesses.^34,35 Furthermore, the gut microbiota produces important vitamins and cofactors, such as vitamin K and several B vitamins, that are required for host metabolic activities.^36,37 The microbiota also metabolizes bile acids, which influence fat digestion and cholesterol metabolism.³⁸ Furthermore, gut bacteria play a role in xenobiotic detoxification, helping to biotransform and excrete potentially hazardous substances.³⁹
• Immune Modulation: The microbiome has a significant impact on immune development and function. It is critical in training the immune system to distinguish between commensal and harmful microorganisms, hence preserving immunological homeostasis. This teaching begins at birth, since maternal microbiome exposure and breastfeeding influence the newborn immune system, supporting the formation of regulatory T cells and other immunological components that limit excessive inflammatory responses.⁴⁰ The gut microbiota also affects systemic immunity by affecting the production of cytokines and other immune mediators. For example, certain microbial metabolites, such as SCFAs, can promote the synthesis of anti-inflammatory cytokines like IL-10 while blocking proinflammatory cytokines like IL-17.⁴¹ This regulation promotes a healthy immune response, which protects against autoimmune disorders and allergies. Furthermore, the microbiota helps to maintain mucosal immunity, especially in the gut. It increases the synthesis of secretory immunoglobulin A (IgA), which is essential for neutralizing pathogens and preventing them from adhering to the gut epithelium.⁴² The microbiota also supports the maturation of gut-associated lymphoid tissues (GALT), which are critical components of the gut’s immune surveillance system.⁴³
• Disease Prevention: The microbiome promotes disease prevention through colonization resistance, where commensal microbes compete with pathogenic bacteria for resources and habitats. This competitive exclusion is critical in preventing infections by opportunistic pathogens like Clostridium difficile, which can thrive when drugs disturb the gut microbiota.⁴⁴ The microbiome also produces antimicrobial peptides and bacteriocins, both of which hinder pathogen growth. Lactobacillus species in the vaginal microbiome, for example, create lactic acid, which keeps the pH low and hostile to many pathogens, protecting against bacterial vaginosis and sexually transmitted diseases.⁴⁵ Furthermore, there is increasing evidence that the microbiome increases the host’s susceptibility to chronic diseases, such as obesity and type 2 diabetes. The composition of the gut microbiota can influence human energy metabolism and fat storage, with specific bacterial profiles linked to an increased risk of metabolic syndrome.⁴⁶ The microbiome’s role in modulating systemic inflammation has been linked to cardiovascular diseases,⁴⁷ autoimmune conditions, and mental health disorders like depression and anxiety,^48,49 indicating its broad impact on overall health.

The microbiome’s functions in digestion, immunological regulation, and disease prevention are critical for human health. Its ability to influence a wide range of physiological processes emphasizes the significance of having a healthy and balanced microbiota. Future studies into the complex interactions between the microbiome and the host will uncover new therapeutic targets as well as disease prevention and treatment options.

Recent Advances and Future Directions in Microbiome Research

Technological Advancements

Recent developments in molecular biology and bioinformatics have greatly improved our knowledge of the human microbiome. The key approaches include:

• NGS: This innovative technology enables the quick and complete sequencing of large volumes of DNA, yielding extensive information on genome structure, genetic variants, and gene expression. Recent advances have boosted the speed, precision, and affordability of NGS, making it more accessible in a variety of research domains.⁵⁰
• 16S rRNA Sequencing: This approach identifies and classifies bacteria and archaea by targeting the 16S ribosomal RNA gene. It provides a taxonomic overview but not functional insights.⁵¹
• Metagenomics: Whole-genome shotgun sequencing analyzes the genetic material of microbial communities, including viruses and fungi, providing a comprehensive view. It exposes the genetic basis of metabolic processes and antibiotic resistance.⁵²
• Metabolomics: Metabolomics is a technology that analyzes metabolites produced by microorganisms to determine their activity. It connects microbial genetic potential to metabolic output, identifying important metabolites such as SCFAs that affect health.⁵³
• Single-Cell Genomics: Single-Cell Genomics involves isolating and sequencing the genomes of individual microbial cells to research unculturable or rare bacteria and comprehend microbial heterogeneity.⁵⁴
• CRISPR-Cas Systems: CRISPR-Cas was originally an adaptive immunological mechanism in bacteria, but it has now been modified for genome editing and regulation in microbiome research. It enables precise modification of microbial genes to investigate their roles.⁵⁵
• Multi-omics Integration: By integrating genomes, transcriptomics, proteomics, and metabolomics, this approach provides a comprehensive understanding of the microbiome’s impact on health and disease. It aids in the creation of tailored therapies by correlating microbial composition with functional outcomes.⁵⁶

These tools have accelerated microbiome research, expanding our understanding of microbial diversity, function, and impact on human health. The future of this subject lies in technical advancements, improved bioinformatics tools, and the integration of multiple “omics” data to provide a comprehensive picture of the microbiome’s involvement in human health.

Integrative Approaches and Future Directions

The combination of 16S rRNA sequencing, metagenomics, and metabolomics, as well as other “omics” techniques such as proteomics and transcriptomics, provides a full understanding of the microbiome. This multi-omics method contributes to a better understanding of host–microbe interactions by correlating microbial composition with functional consequences.⁵⁷ Future research will most likely focus on improving the resolution and accuracy of these methodologies, as well as building better bioinformatics tools for data integration.^50,58

Future studies will seek to better understand the mechanisms behind host–microbiome interactions and their consequences for health. Key areas of focus include investigating how nutrition, antibiotics, and environmental variables affect microbiome composition and function.⁵⁹

The Microbiome’s Role in Various Diseases

Recent research has emphasized the human microbiome’s crucial role in a wide range of diseases, including metabolic disorders, cancer, IBD, and mental health concerns (Figure 2). These findings highlight the microbiome’s impact on host physiology and prospective treatment targets. Here, we look at major research that sheds light on the microbiome’s role in certain health issues.

Metabolic Disorders

There is emergent evidence that changes in the microbiota composition can cause a variety of disorders, including metabolic diseases like obesity and diabetes.⁶⁰ Turnbaugh et al.discovered that obese people have a different gut microbiome composition than lean people, with a larger proportion of Firmicutes relative to Bacteroidetes.⁶¹ This altered microbial composition is expected to improve energy extraction from the food, leading to increased adiposity. Qin et al. discovered that changes in gut microbiota composition and function are linked to insulin resistance and systemic inflammation in type 2 diabetes patients, implying that the microbiome is involved in the disease’s pathophysiology.⁶²

Cancer

The gut microbiota has a substantial impact on host health and has been connected to cancer development.⁶³ It also affects extra-intestinal malignancies such as hepatocellular carcinoma via organismal dissemination.² Helicobacter pylori has been linked to stomach cancer, and some bacterial species such as Fusobacterium and Clostridium are overrepresented in patients.⁶⁴ Breast cancer growth has been connected to certain bacterial populations, with pathogenic strains such as Escherichia coli and Staphylococcus epidermidis causing DNA damage in malignant tissues.⁶⁵

Inflammatory Bowel Disease

Dysbiosis, or an imbalance in the gut microbiota, can cause autoimmune disorders including IBD.⁶⁶ A disrupted mucus layer can compromise the integrity of the gastrointestinal barrier, which is crucial in avoiding inflammation, resulting in increased proinflammatory and decreased anti-inflammatory cytokines.⁶⁷ Researchers discovered alterations in genes involved in microbiome–immune interactions in IBD patients.⁶⁸

Cardiovascular Diseases

The gut microbiota produces compounds such as trimethylamine N-oxide, which have been associated with cardiovascular disease by altering lipid metabolism and causing atherosclerosis.⁶⁹ Dysbiosis is related to an increased risk of cardiovascular disease, with studies revealing changed gut flora in hypertension individuals.⁷⁰

Systemic Infections from Bacterial Translocation

Bacteria can spread from the gut to other body regions, especially in immunocompromised people, resulting in systemic infections.⁷¹ Disturbance of the gut microbiota and epithelial injury increases the probability of pathogen translocation such as E. coli and K. pneumoniae.⁷² Uremic toxins produced by dysbiotic flora can cause systemic inflammatory responses, which contribute to disorders such as chronic kidney disease.⁷³

Allergic Diseases

The human microbiome influences allergy illnesses, with dysbiosis impacting lung microbiota and increasing respiratory disease threat.⁷⁴ Cesarean delivery, which avoids normal maternal flora transmission, is associated with increased allergy risk in offspring. Lower microbial diversity in early life has been linked to increased allergy sensitivity, such as asthma.⁶⁶

Health Maintenance

The microbiome is essential for maintaining homeostasis,⁷⁵ activating the immune system,⁷⁶ and controlling inflammation.⁷⁷ It also helps eliminate toxic compounds⁷⁸ and plays a role in immunological responses in the female vaginal tract, contributing to infection resistance.⁷⁹

Mental Health

Dysbiosis, or microbial imbalance, may contribute to the onset and progression of mental diseases.^80,81 The term “psychobiotics” refers to probiotics that improve mental health by modulating the microbiome.⁸² This points to possible therapeutic options for treating mental health issues by targeting the gut microbiome. These significant studies emphasize the microbiome’s role in a variety of diseases, emphasizing its potential as a biomarker for disease risk and development, as well as a therapeutic intervention target. Ongoing research into the microbiome’s role in health and disease continues to reveal complex host–microbe interactions, providing new insights into disease causes and opening up new therapy and preventative options.

Microbiome Modulation: Therapeutic Approaches

Probiotics and Prebiotics: Efficacy and Challenges

Extensive research and clinical evidence have shown that probiotics and prebiotics are beneficial in restoring gut microbiota equilibrium and treating a variety of disorders. Probiotics are live bacteria that, when taken in suitable concentrations, provide health advantages. Prebiotics are nondigestible food components that encourage the growth of good microorganisms. Both have the potential to transform illness management.^83,84

Probiotics: Efficacy and Mechanisms

Probiotics, which are usually found in the genera Lactobacillus, Bifidobacterium, and Saccharomyces,⁸⁵ work in numerous ways to provide health benefits:

• Enhancement of Gut Barrier Function: Probiotics enhance gut barrier function, preventing infections and poisons from entering the bloodstream.⁸⁶
• Immunomodulation: Mazziotta et al. found that they influence the immune response by boosting anti-inflammatory cytokines, increasing regulatory T-cell activity, and producing bacteriocins to suppress harmful bacteria.⁸⁷
• Competition with Pathogens: Probiotics compete with harmful bacteria for nutrients and adhesion sites, reducing infections.⁸⁸
• Recent studies have shown that probiotics can reduce the duration and severity of acute infectious diarrhea in children,⁸⁹ improve symptoms of irritable bowel syndrome (IBS),⁹⁰ and boost the immune response to vaccinations.⁹¹

Prebiotics: Efficacy and Mechanisms. Prebiotics preferentially enhance the development and activity of beneficial gut bacteria, resulting in the synthesis of SCFAs such as acetate, propionate, and butyrate, which have health-promoting properties:⁹²

• Promotion of Beneficial Microbiota: Prebiotics promote the growth of beneficial bacteria like Bifidobacterium and Lactobacillus, leading to a balanced and healthy microbiota composition.⁹³
• Production of SCFAs: SCFA production is important for gut health, as butyrate provides energy to colonocytes, promotes gut barrier integrity, and has anti-inflammatory properties.⁹⁴
• Modulation of Lipid Metabolism: Prebiotics reduce blood cholesterol levels and change bile acid metabolism, which is partially mediated by SCFA.⁹⁵

Prebiotics have been found to promote gut health, increase mineral absorption, lower the risk of colorectal cancer,⁹⁶ and help control metabolic disorders like obesity and type 2 diabetes by improving metabolic profiles.⁹⁷ Fecal Microbiota Transplantation: Current Status, Applications, and Controversies. Fecal microbiota transplantation (FMT) (Figure 3) is the process of transferring stool from a healthy donor into a recipient’s gastrointestinal tract to reestablish a balanced and diversified gut microbiota in patients suffering from dysbiosis.⁹⁸

Applications of FMT FMT is a conventional treatment for recurrent Clostridium difficile infection (CDI) when traditional antibiotics fail. It restores gut microbiota and suppresses C. difficile growth through food competition and immune system stimulation.⁹⁹

• IBD: FMT is an investigational treatment for IBD, including Crohn’s disease and ulcerative colitis. Some studies suggest beneficial outcomes, such as remission or symptom reduction, but the results are variable, and FMT is not yet considered a standard treatment for IBD.¹⁰⁰
• IBS: FMT may help with IBS, although results depend on donor selection and patient variables.¹⁰¹
• Metabolic Syndrome and Obesity: Early studies indicate that FMT from lean donors can temporarily increase insulin sensitivity in obese recipients, suggesting potential metabolic benefits. However, long-term efficacy and safety remain unknown.¹⁰²
• Neuropsychiatric Disorders: Preliminary studies and case reports on FMT for neuropsychiatric disorders, such as autism and depression, have yielded inconsistent results. More study is required to better understand the mechanisms and treatment benefits.¹⁰³

Diet and Lifestyle Interventions: Modulating the Microbiome and Implications for Health.

The human microbiome, particularly the gut microbiota, is a dynamic ecosystem impacted by diet and lifestyle, which can alter its composition and function, affecting general health and disease risk. Recent research emphasizes the ability of dietary and lifestyle interventions to regulate the microbiome, hence enhancing health and avoiding or alleviating illnesses.

Dietary Influences on the Microbiome

Diet is a primary modulator of gut flora.

• High-Fiber and Complex Carbohydrate Diets: Encourage beneficial bacteria such as Bifidobacterium and Lactobacillus to create SCFAs for health benefits.¹⁰⁴
• High-Fat Diets: High-fat diets can reduce microbial diversity and boost proinflammatory microorganisms.¹⁰⁵
• Polyunsaturated Fats and Plant-Based Proteins: Polyunsaturated fats and plant-based proteins promote beneficial microorganisms.¹⁰⁶
• Polyphenols: Polyphenols, found in fruits, vegetables, tea, and wine, improve gut health by boosting beneficial bacteria and SCFA production.¹⁰⁷

Lifestyle Factors Affecting the Microbiome

Several lifestyle factors have a substantial influence on the gut microbiome:

• Physical Activity: Regular exercise enhances microbial diversity, and SCFA-producing bacteria, improves gut barrier function, and reduces inflammation.¹⁰⁸
• Sleep and Circadian Rhythms: Poor sleep and altered circadian rhythms can promote dysbiosis, resulting in inflammation and metabolic disorders.¹⁰⁹
• Stress and Psychological Factors: Chronic stress can negatively impact the gut–brain axis, leading to increased gut permeability and inflammation, which can worsen gastrointestinal and mood disorders.¹¹⁰
• Medication Use: Antibiotics and other drugs can change the microbiome, leading to reduced diversity and pathogen overgrowth, affecting gut health.¹¹¹

Challenges and Debates in Microbiome Research

Microbiome research has advanced rapidly, revealing the vital role that microbial communities play in human health and disease. The heterogeneity of study outcomes presents a significant problem in this subject, making replication and interpretation challenging. This variation is mostly due to individual variances in microbiome composition and function, which are influenced by genetics, diet, lifestyle, environment, and host physiology. Addressing these discrepancies is critical to improving the dependability of research findings and their use in therapeutic settings.

Factors Contributing to Interindividual Variability

Several variables affect interindividual variability in microbiome studies:

• Genetic Influences: Host genetics influence immunological responses, metabolism, microbial colonization, and community organization. Genetic differences, particularly in immunological function genes, might influence host–microbe interactions, with research indicating heritability in gut microbiota composition across related individuals.¹¹²
• Diet and Lifestyle: Dietary choices and lifestyle factors including physical activity, stress, and sleep patterns have a substantial impact on the microbiota. High-fat diets, for example, may reduce beneficial bacteria while increasing proinflammatory bacteria.¹¹⁰
• Environmental Factors: Geographical location, sanitation, pollution, and antibiotic use can impact microbiome composition. Environmental variables, such as cleanliness levels and urban/rural living situations, contribute to variability.¹¹³
• Age and Developmental Stage: The microbiome evolves from infancy to maturity, impacted by nutrition, medication usage, and immune system alterations in the elderly.¹¹⁴

Ethical and Privacy Concerns: Issues Related to Microbiome Data Privacy and Ethical Considerations

Microbiome research, despite its potential, raises serious ethical and privacy problems. The unique and individualized character of microbiome data raises concerns about consent, data ownership, confidentiality, and potential misuse.

• Privacy and Data Security: Microbiome data might expose sensitive information about a person’s health, lifestyle, and genetics. Even anonymized data is at risk of being re-identified, particularly with big data analytics. Protecting privacy requires robust data security and transparent data exchange policies.¹¹⁵
• Informed Consent and Data Ownership: It can be tough to ensure participants understand the breadth of data collection and future usage. Clear consent forms and open communication regarding data usage and ownership are critical. Participants should also understand their rights, which include the ability to withdraw from studies.¹¹⁶
• Ethical Use of Microbiome Data: The potential applications of microbiome data in healthcare and elsewhere create ethical concerns concerning access and use. Concerns include discrimination in insurance or employment based on microbiome characteristics, as well as the marketing of microbiome products that may make deceptive promises.¹¹⁷
• Equity and Access: Microbiome research should benefit all populations to prevent health inequities. Researchers and policymakers must devise measures to promote equal access to microbiome-based treatments and diagnostics.¹¹⁸
• Environmental and Public Health Considerations: Research on environmental samples might yield significant insights, but it must adhere to privacy and environmental ethics. Monitoring microbial populations in public and private settings necessitates careful consideration of these variables.¹¹⁹

Future Directions and Research Gaps in Microbiome Research

Challenges and Research Gaps

Microbiome research has shown complicated relationships between microbial ecosystems and human health, with implications for therapeutic interventions and customized medicine. However, significant problems and research gaps must be addressed, with an emphasis on three key areas:

• Personalized Microbiome-Based Therapies: Developing tailored microbiome-based therapies is problematic due to considerable heterogeneity in microbial populations among individuals.¹²⁰
• Longitudinal Studies: Longitudinal studies are needed to understand the evolution of the microbiome and its impact on health and disease progression, which is currently under-researched.¹²¹
• Integration with Other “Omics” Technologies: Integrating microbiome data with other “omics” technologies (genomics, proteomics, and metabolomics) is crucial for a comprehensive understanding of the microbiome’s role in health and disease. However, this requires advanced analytical methods and interdisciplinary collaboration.¹²²

Addressing these issues will be critical for furthering microbiome research and converting results into therapeutic applications.

Implications for Future Research and Public Health

The impact of microbiome research on healthcare practices and policies is significant. As we get a better understanding of the microbiome’s involvement in health and disease, we should expect more tailored and preventive healthcare methods. For example, microbiome analysis could become a common diagnostic technique, leading to tailored therapies such as food changes, probiotics, or microbiome transplants.³³

Furthermore, incorporating microbiome data into electronic health records and public health surveillance systems may improve the ability to monitor and manage infectious disease outbreaks, track antibiotic resistance, and understand population health trends. This research has the potential to inform public health policies and programs aimed at promoting healthy microbiome compositions in various groups.¹²³

However, these improvements highlight the need for strong regulatory frameworks to assure the safety and efficacy of microbiome-based goods and services. Policymakers will need to address ethical concerns about data privacy and equal access to microbiome-based healthcare breakthroughs.

Microbiome-Based Pharmaceuticals

Microbiome-based pharmaceuticals, sometimes known as “pharmabiotics,” include live bacterial therapies, bacteriophages, and microbial metabolites intended to treat certain disorders (Figure 4).

• Live Bacterial Therapeutics: These use genetically created or naturally existing microorganisms to provide therapeutic effects. For example, E. coli Nissle 1917 is utilized to treat gastrointestinal diseases.¹²⁴
• Bacteriophages: Bacteriophages are viruses that selectively infect and kill bacteria. They provide a tailored method for eradicating harmful germs while preserving healthy microorganisms. Phage treatment is being investigated for antibiotic-resistant infections and other bacterial disorders.¹²⁵
• Microbial Metabolites: SCFAs and other microbial metabolites have therapeutic potential.¹²⁶ Butyrate, an SCFA generated by gut bacteria, has anti-inflammatory characteristics and is being studied as a treatment for IBD and metabolic diseases.¹²⁷

Challenges and Future Directions

While microbiome-based therapeutics show significant promise, numerous issues must be addressed:

• Individual Variability: The human microbiome is extremely personalized, impacted by genetics, food, environmental factors, and lifestyle. Personalized techniques are required to ensure the effectiveness of microbiome-based therapeutics.
• Safety and Regulation: Ensure the safety and efficacy of microbiome-based medicines through thorough clinical testing and regulatory control. Standardizing practices and creating clear regulatory frameworks are critical.
• Mechanistic Understanding: More research is needed to determine how the microbiota affects health and disease. This understanding will help to design tailored medicines and enhance clinical outcomes.

Conclusion

The human microbiome has a significant impact on digestion, immunological function, and disease prevention. Advances in molecular biology have helped us better comprehend these microbial ecosystems. Probiotics, prebiotics, and FMT are therapeutic approaches that show promise in treating a variety of disorders by restoring microbial balance. Diet, exercise, and stress management have a substantial impact on the microbiota.

Despite its potential, microbiome research confronts numerous hurdles, including individual diversity and ethical considerations. Personalized medicines necessitate a thorough understanding of individual microbiomes, requiring additional study and ethical considerations. Integrating microbiome data into healthcare could transform illness management and lead to more effective, individualized therapies, underscoring microbiome research’s bright potential in improving human health.

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Cite this article as:
Fahmy A. Microbiome and Human Health: Recent Insights and Future Directions. Premier Journal of Public Health 2024:1;100002

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