The human gastrointestinal (GI) tract represents a complex environment filled with a diverse range of microbes [1]. The gut microbiota is composed of numerous bacteria, archaea, fungi, and viruses, with bacteria being the most studied. This microbial community colonizing the GI tract has co-evolved with the host over thousands of years and forms an intricate and mutually beneficial relationship. The microbiota offers many benefits to the host through a range of physiological functions. However, as a result of an altered microbial composition, these mechanisms can be disrupted, leading to diseases. There is an increase in evidence that the gut microbiota composition profoundly affects gut integrity and host health.
1. Introduction to the Gut Microbiome
In recent decades, there has been increased interest in gut microbiota, profiling its composition, and understanding its impact on health and disease [2]. Diet is one of the most significant factors that influence gut microbiota composition. There is an intricate and complex interaction between nutrition and microbiota. During the digestive process, the food ingested is processed through the digestive tract, which is colonized by a huge diversity of microbes. These microbes can modulate host physiology and affect immunity, nutrient absorption, metabolism, and the generation of vitamins. Trillions of microbes inhabit the human gut, with a significant impact on many aspects of health, metabolism, physiology, nutrition, and immune function. The human gut microbiome is thought to comprise diverse groups of symbiotic and opportunistic pathogens.
1.1. Definition and Composition
The gut microbiome is the microbial community that lives in the gastrointestinal tract of humans. It contains trillions of microorganisms, including bacteria, archaea, fungi, and viruses that co-habit the relatively small space of the gut. The gut microbiome has a massive metabolic capacity that interacts with the host gut epithelium and other systems. The adult human gut microbiome is generally stable in composition but is affected by many host and environmental factors, including age, diet, geography, antibiotic treatment, and diseases, and it can be a marker of environmental changes (e.g., diet) and health conditions. The gut microbiome has been shown to affect the host immune system, metabolic functions, drug metabolism, and neurological and psychological processes [3]. However, further research is required to understand the mechanisms of action and establish causality.
Human gut microbiota are composed of several species of microorganisms, including bacteria, yeast, and viruses. Only a few phyla are represented, accounting for more than 160 species. The dominant gut microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia, with the two phyla Firmicutes and Bacteroidetes representing 90% of gut microbiota. The Firmicutes phylum is composed of more than 200 different genera such as Lactobacillus, Bacillus, Clostridium, Enterococcus, and Ruminicoccus. Clostridium genera represent 95% of the Firmicutes phyla. Bacteroidetes consists of predominant genera such as Bacteroides and Prevotella. The Actinobacteria phylum is proportionally less abundant and mainly represented by the Bifidobacterium genus. Human gut microbiota vary taxonomically and functionally in each part of the GI tract and undergo variations in the same individual due to infant transitions, age, and environmental factors such as antibiotic use.
2. Methods for Studying the Gut Microbiome
One essential technique for the characterization of microbial communities is sequencing the gene coding for the 16S ribosomal RNA (rRNA) component of the ribosome. All microbial cells contain ribosomes, consisting of a rRNA and protein portion. In phylogeny, ribosomal RNA genes have several desirable properties, including a relatively constant function, a conserved structure which allows for the inference of phylogenetic trees, and that their sequences can be aligned and characters scored at the same time. Additionally, the 16S rRNA sequences of members of all known prokaryotic phyla are recovered from a single DNA amplification step. These genes have regions which are highly conserved across species interspersed with regions of hypervariability allowing for discrimination between closely related species [4].
There are two ways to conduct 16S rRNA sequencing. In direct sequencing, 16S sequences are recovered from environmental samples, and they are then phylogenetically classified. Because they reflect the state of the environment at the time they were recovered, they are often described as “in situ.” In comparison, in enrichments, the microbial community’s activity is influenced by artificially created conditions (e.g., carbon source or growth temperature). These samples are then processed through imaging, phospholipid analyses, or kinetic studies followed by 16S rRNA sequencing. Because they are often analyzed without genetic sequencing, they are described as “ex situ” [5].
2.1. 16S rRNA Sequencing
The gut microbiome, an intricate and diverse community of microorganisms inhabiting the gastrointestinal tract, has gained significant attention in recent years due to its crucial role in maintaining the overall health of the host. It consists of a wide range of bacteria, viruses, archaea, fungi, and other eukaryotes, which collectively outnumber human cells and carry unique genetic information [6]. Advances in high-throughput sequencing technologies and bioinformatics tools have enabled researchers to explore the gut microbiome’s complex structure and function with high resolution and throughput. While most of our knowledge about the gut microbiome has been derived from studies of its bacterial component, other groups of microbes, like viruses, archaea, and fungi, also populate the gut environment.
The 16S rRNA gene, a highly conserved gene among all bacteria, has been widely used to investigate the composition and diversity of bacterial communities through a culture-independent approach known as 16S rRNA sequencing. The progress in sequencing technologies and the general acceptance of bioinformatics methods for analyzing 16S rRNA data have facilitated the global investigation of bacterial communities and their roles in the gut environment across diverse populations of human and non-human species [7]. Although there are well-established protocols for 16S rRNA sequencing studies, some important steps may significantly impact the outcome and interpretation of the results.
3. The Gut Microbiome and Digestive Health
The gastrointestinal (GI) tract represents one of the largest interfaces between the host, environmental factors and antigens in the human body. The collection of bacteria, archaea and eukarya colonising the GI tract is termed the ‘gut microbiota’ and has co-evolved with the host over thousands of years [1]. The number of microorganisms inhabiting the GI tract has been estimated to exceed 10 14 , which encompasses ∼10 times more bacterial cells than the number of human cells. It is primarily a bacterial ecosystem comprising ∼500–1500 species of microorganisms and represents a unique and complex ecosystem in terms of microbiota diversity compared to other anatomical sites. On a species level, the human gut microbiota appears to be more similar between subjects than on a genetic (strain) level. Some gut commensals are associated with the human enterotype as a function of the individual microbiota. The microbiota offers many benefits to the host, such as strengthening gut integrity, harvesting energy, protecting against pathogens, and regulating host immunity. However, there is potential for these mechanisms to be disrupted as a result of an altered microbial composition, known as dysbiosis. The gut microbiota is thought to play a central role in metabolic control, and metabolic diseases such as obesity and type 2 diabetes are associated with unbalanced gut microbiota compositions.
The gut microbiota has a central role in digestion. Unlike many mammalian species, humans have a comparatively low fibre fermentation capacity in the upper GI tract, and only ∼5% of dietary fibre is fermented in the stomach and jejunum. This is primarily due to the human gastric juice with a high pH and insufficient activity of pancreatic enzymes. Therefore, the majority of dietary fibre is subjected to gut fermentation [2]. During gut fermentation, gut microbiota utilize dietary fibre and release SCFAs. These microbes also produce a variety of metabolites that ultimately modulate gut function and host physiology. In general, gut microbes digest polysaccharides into monosaccharides and then ferment mono- and oligosaccharides to SCFAs and gases. The balance between different microbial species may impact digestive function on a biochemical level. The gut microbiota can digest polysaccharides until SCFAs, while the host can convert SCFAs into other products.
3.1. Role of Gut Microbiota in Digestion
The intricate and diverse collections of gut microbiota are responsible for a variety of biochemical processes that are integral for digestion and for the utilization of nutrients [1]. Different microbial populations occupy different substrates in the digestive system like the stomach, small intestine or large intestine. Each niche represents a different selective environment which offers distinct carbohydrate and nitrogen sources for microbial metabolism. Microbial metabolism is responsible for crucial components of nutrition, energy harvesting and absorption of carbohydrates, proteins and lipids that would otherwise be indigestible or nonbioavailable. More specific contributions of microbial communities to digestion, protection from allergens, pathogenic bacteria and inflammation are also recognized and are considered to be equally important [2]. Increasing evidence also implicates the gut microbiome in the regulation of metabolism and storage of fats and in the control and development of further disorders such as obesity or diabetes. However, this knowledge remains often associative while more mechanistic understanding is required to further explore the role of the gut microbiome for the digestion and overall health.
4. The Gut Microbiome and Immune Function
The gut microbiome, a community of trillions of microorganisms residing in the gastrointestinal tract, interacts intimately with the host across the gut epithelium and is thought to play an important role in shaping both the innate and adaptive immune systems. Dysbiosis is defined as a change of microbiota composition from eubiosis and a significant decrease in microbiota diversity is a typical sign of dysbiosis. The cross-talk between the gut microbiome and the immune system and dysbiosis-linked disorders of the immune system have been extensively investigated [8]. Oral ingestion of antigens is important for the development of tolerance. Environmental factors including the gut microbiome are important for establishing tolerance and shaping T cell immunity. Studies have shown that gut microbiome-derived microbial metabolites, microbial markers, and certain microorganisms induce intestinal Tregs, and alter the differentiation and activation of Th17 and Th1 cells [9]. However, gut microbiome composition differs among individuals, and dysbiosis leads to the development of various immune-mediated disorders. With the development of sequencing technology, animal models, and bioinformatics resources, numerous studies have revealed the correlation between gut microbiota and the immune system. This review discusses the role of the gut microbiome in activating T cells, and the development and promotion of autoimmune diseases and various cancers.
4.1. Interactions with the Immune System
The gut microbiome, consisting of the substantial community of microbial cells in the intestinal tract, actively interacts with the human immune system to influence immune development and response. Commensal microbes account for the colonization of gut microbiota, which involves the co-development of the gut microbiome and the immune system [10]. Even during early life, microbial presence and complexity relate to immunity, gut maturation, and growth, with differences in gut microbiome diversity correlating with the maturation of the immune system. The development of the immune system in germ-free organisms was impaired, with reductions in microfold cells, dendritic cells, IgA-producing plasma cells, and production of anti-inflammatory cytokines (such as IL-10), as well as increases in pro-inflammatory cytokines (such as IL-6) [9]. Adaptive immune system development was less pronounced in germ-free mice with reduced T- and B-cell formation and responsiveness. The presence of microbiota also contributes to the formation of gastrophilic IELs, IgA-producing plasma cells, and SCFA role in inducing Treg differentiation. The composition of gut microbiota activities and fermentation of SCFA and peptidoglycan to specific gut mucosal immune cells was also identified. A large number of immune-associated signaling pathways, including the NF-κB, MAPK, and NOD pathways, were induced by peptidoglycan. Overall, these findings support the notion that gut microbiota contributes to the development of intestinal mucosal immune system components and the possible distinct mechanisms that occur with different types of gut microbes.
The noted interactions between gut microbiota and the immune system are complex and have profound implications for the understanding of how all components of the immune system work together. A fundamental question that has major implications for immune function is how systemic IgG responses are generated to the gut microbiome. Disruption of the microbiome drastically changes the composition and diversity of circulating IgG and IgA antibodies. Several mechanisms have been proposed for the generation of IgG responses to gut microbiota, which appears to depend on a complex interplay of host genetics, luminal microbial composition and activity, and distinct transport pathways for luminal antigens through the gut barrier to the systemic compartment. Such pathways include the transcellular transport of antigens by mucosal M cells in conjunction with dendritic cell sampling in the gut. Intestinal antigens may also cross through the gut epithelium via the paracellular route. It is plausible that no one particular pathway is responsible for IgG responses to the gut microbiome, but that unique mechanisms may operate depending on distinct environmental settings such as stress, diet, or inflammation.
5. The Gut Microbiome and Mental Health
The gut microbiome has been associated with the central nervous system and the development of neuropsychiatric diseases and is believed to play an important role in the life-long peripheral regulation and modulation of neurology, neuronal plasticity, cognition, and behavior [11]. Physiologically, the gut is connected to the central nervous system through a biochemical signaling pathway known as the gut-brain axis, involving the complex cross-talk between the gastrointestinal tract and the brain. The gut-brain axis seems to contribute to the baselines of emotional, cognitive, and behavioral development, and it is disrupted by virtually all neuropsychiatric disorders. MPG trauma-induced stress and dysbiosis impact this cross-talk through impaired neurotransmitter synthesis and availability, modulating gut and brain cellular metabolism and bioenergetics and impacting neurogenic niches and the integrity of the blood-brain barrier. Emerging but limited preclinical research indicated that the gut microbiome also influences neurodevelopment, cognition, and memory in a sex-dependent manner.
Understanding how the gut microbiome, a newly discovered organ, affects health and disease is one of contemporary medicine’s biggest challenges. This ecosystem of trillions of bacteria, viruses, fungi, and other microbes resides in a complex community in the gastrointestinal tract of all mammals, and it co-evolves with the host over long periods. In addition to finely tuned mechanisms that co-regulate gastrointestinal physiology, anatomy, immunology, and neurology, there is a gut-brain axis that has been understood for many years [12]. Nevertheless, new insights into the current state of research on the gut microbiome and brain alterations in the fields of neurology and psychiatry are reviewed here. Notably, emerging but limited preclinical studies suggest that gut microbes could alter human behavior and cognition through host-neuronal mechanisms rather than through peripheral pathways.
5.1. The Gut-Brain Axis
The gut-brain axis, or bidirectional communication between the gut and the brain, is an intricate and still-mysterious relationship that may have wide-reaching implications for everything from anxiety and depression to neurodegenerative diseases and brain injuries. While the brain clearly influences bodily functions such as digestion, new evidence suggests that complex signalling pathways link gut microbiota to processes as disparate as mood regulation and neuroprotection. The gut–brain axis may be involved in the emergence of neurological and psychiatric disorders, as well as in recovery from peripheral nervous system damage [11]. The term “gut-brain axis” (GBA) usually refers to functional and anatomical bidirectional communication and feedback between the gastrointestinal (GI) or gut system and the central nervous system (CNS) [13]. Several pathways may contribute to this inter-organ communication, including the autonomic nervous system (ANS), especially parasympathetic vagus nerves, the enteric nervous system (ENS), hormones, the immune system, and microbial factors (i.e., metabolites, proteins, and small RNAs) in the lumen of the GI tract. All these mechanisms may play a role individually or in combination. Dysregulation along the gut-brain axis could contribute to the pathophysiology of both GI and neurological disorders. The concept of “microbiota-gut-brain axis” was introduced in 2010 to emphasize the role of living microorganisms within the GBA. The gut microbiota may influence the brain and behavior through multiple mechanisms, including modulation of the gut barrier, the enteric nervous system, ANS signaling, the vagus nerve, production of neurotransmitters, and metabolic products such as short-chain fatty acids (SCFAs). These signalling pathways may affect plasticity, neurogenesis, and the immune response in the brain and may also modulate both local and systemic inflammatory processes.
6. Factors Influencing the Gut Microbiome
Gut microbiomes are influenced and modulated by both environmental and host factors [14]. Environmental factors include the mode of birth, diet, and exposure to microbial organisms, while host factors include genetics, age, and sex. Dietary choices directly affect the composition and function of gut microbiomes, which in turn can affect host physiology through mechanisms such as microbial metabolism, the production of metabolites involved in immune development, and stimulating the growth and differentiation of epithelial cells [2]. Consideration of dietary choices in study design, data analysis, and interpretation of gut microbiota variations leads to meaningful discoveries outside the scope of conventional investigations and illuminates modifiable factors that affect gut microbial communities. In this study, the impacts that diets high in animal protein, fat, carbohydrates, and polyunsaturated fats have on gut microbiomes and health are examined. These diets not only discuss their relationships with gut microbiomes and bodily functions but also elaborate on evidence-based dietary factors of potential use in sustaining or restoring healthy gut microbiomes.
6.1. Dietary Choices
Dietary choices are instrumental to gut microbiomes. Nutrition directly shapes the composition and dynamics of microbial populations within the gut environment; therefore, dietary composition affects microbiota composition, influencing microbe-derived metabolites and their signaling to the host [2]. Ingestion is the principal way through which gut microbial communities are established and maintained over a person’s lifetime. Commensal bacterial communities take root in the gut after birth, shifting as dietary inputs change, which is especially significant during transitions from breastfeeding to solid food. Diets can support or inhibit the outgrowths of particular strains; for instance, certain bacteria in human breast milk cannot be found in cow’s milk, resulting in microbiota differences as children ages. Additionally, ongoing dietary inputs further refine microbial diversity by either promoting or inhibiting specific taxa according to dietary composition.
Dietary fat content and sort affect gut microbiota configuration. High-fat diets strongly affect the composition and diversity of gut microbiomes, leading to shifts in microbial biogeographic patterns. Dietary fibers exert selective pressures towards the outgrowth of fiber-degrading bacteria, promoting community coalescence and species richness, and these shifts may be maintained over time. Emerging knowledge shows gut microbiomes are tightly linked with the broader metabolic network, potentially fundamental to host fitness. Other dietary factors identified to affect gut microbiota include complex carbohydrates, proteins, prebiotics, and probiotics. Thus, dietary composition is crucial for maintaining healthy gut microbiomes, and recent work indicates specific dietary components can restore microbiomes to a desirable state after disturbance.
7. Dysbiosis: Imbalance in the Gut Microbiome
The gut microbiome can be disrupted by a variety of factors. This disruption, called dysbiosis, can affect the gut microbiome balances between communities of different types. Diet is one of the factors mentioned and addresses the dietary components that are not digested by host enzymes may deliver a variety of growth-promoting and growth-inhibiting factors that influence the balance between microbial species [2]. Although daily diet greatly affects gut microbial balance, it also has important implications for physiology and health. This is because the gut’s processing of the human diet can regulate human responses to food types depending on the inhabitant’s microbiome. Consequently, dietary increase or decrease of certain nutrients can affect host health status by modulating the composition and diversity of the gut microbiome. Then, dysbiosis can lead to impaired digestion and absorption. And also may have important implications beyond the gut, contributing to the development of a wide range of extra-intestinal diseases including metabolic, cardiovascular, central nervous system, and depressive disorders [15].
7.1. Causes and Consequences
Dysbiosis, or an imbalanced gut microbiome, can arise from numerous factors. Diet plays a major role in shaping the gut microbiome, and diets high in refined sugars, saturated fats and artificial sweeteners can promote dysbiosis [2]. Additionally, a typical Western diet, containing excessive amounts of refined sugars and fats, can raise levels of microbes associated with metabolic disease and obesity. This diet usually leads to an overgrowth of microbes that take advantage of the food supply to produce substances that can foster low-grade inflammation, a well-recognized contributor to metabolic disorders. Conversely, diets high in fiber-rich foods can favour gut microbes that produce short-chain fatty acids (SCFA), such as acetate and butyrate. SCFA can induce anti-inflammatory responses and modify host metabolism, providing pathways through which dietary choices can positively affect host health. In addition to diet, the use of antibiotics can lead to dysbiosis, as antibiotics reduce the diversity of the gut microbiome and increase microbes that can thrive in the absence of competition from other species. Stress also has negative effects on the gut microbiome. Studies on childhood stress, including physical abuse or neglect, indicate that such experiences can reduce microbial diversity and promote overgrowth of inflammatory species in adulthood. While the consequences of these lifestyle choices can be insidious, they usually provide a pathway toward gradual increases in the levels of bacteria that dysregulate processes underlying overall health [1].
8. Probiotics and Prebiotics
Probiotics refer to living microorganisms, mainly bacteria and yeast, which can beneficially affect the host when administrated in sufficient amounts [16]. Probiotics have been in use for many years, mainly in dairy products for the treatment of gastrointestinal diseases. The beneficial action of the strain Lactobacillus casei Shirota was documented in 1930 and assumed that it improved human health through modification of gut microflora. Since then, probiotics have been used for the treatment of various diseases of the gastrointestinal tract. However, the most documented effects of probiotics have been associated with diarrhea, mainly antibiotic-related and infectious diarrhea. The health benefits of using probiotics in food and dietary supplements encompass the prevention and reduction of the severity of diseases such as obesity, insulin resistance syndrome, type 2 diabetes, and non-alcoholic fatty liver disease. Probiotics also prevent and control respiratory infections caused by viruses and bacteria. Furthermore, they augment the body’s immunity through the activation of dendritic cells and the increased production of immunoglobulin A. Probiotics can change the composition of the gut microbiota and prevent the progression of several diseases, including cancer. They outcompete pathogens for nutrients and adhesion sites and inhibit their growth by producing antimicrobial substances. Clinical studies have proven the effectiveness of probiotics for treatment of a number of diseases in humans. Some probiotic strains, however, can have pro-inflammatory effects and are not recommended for patients after transplantation. Commonly administrated probiotic strains are Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb12, Streptococcus thermophilus, or Lactobacillus reuteri. Recommended doses of probiotics differ and depends on the particular case. Tolerance and effectiveness of probiotics are strain-dependent, and different strains should be tested in treatment. Several prebiotics are utilized by intestinal microbiota and can modify the gut microbiome [17]. This modification can prevent diseases associated with gut microbiota composition imbalance. Probiotic and prebiotic supplementation can sustain the function of the gut microbiome in the well-state. Continuous consumption of functional foods containing probiotics and prebiotics is needed to prevent the development of diseases and to improve health.
8.1. Role in Gut Health
Gut health significantly depends on gut microbiota, and maintaining a healthy gut microbiome is important. Ingesting probiotics (live microbes) is an effective way of maintaining a good intestinal flora. Probiotics have positive effects on human health, as they reduce the side effects caused by antibiotic usage, prevent diarrhea and colitis, and decrease the incidence of certain strains of pathogens like Escherichia coli O157:H7 and Clostridium difficile [2].
Probiotics are most commonly ingested in food, dairy products, and fermented foods such as yogurt, cheese, and sauerkraut. Probiotic microbes used in dairy products may be normal gut commensal bacteria. Most of these probiotic microbes belong to the genera Lactobacillus, Bifidobacterium, or Streptococcus, and different strains of probiotic microbes have distinct health-promoting activities [17]. Probiotic microbes may produce a variety of antimicrobial compounds such as lactic acid, hydrogen peroxide, and bacteriocins; regulate local and systemic immune responses; promote absorption of nutrients; and produce different groups of vitamin B.
9. Therapeutic Potential of Modifying the Gut Microbiome
Modifying the gut microbiome promises to be a fascinating and novel approach to disease management. There have been simple physical approaches that assess diet intake, including supplements, prebiotics, and probiotics. Prebiotics are non-digestible or slowly fermentable carbohydrates, which selectively stimulate the growth and/or activity of beneficial bacteria. Probiotics are live microorganisms, which provide health benefits on their host when taken in adequate amounts [18]. Such microorganisms are currently used for the treatment of inflammatory bowel disease, lactose intolerance, diarrhea, constipation, obesity and diabetes. Targeted manipulation of the gut microbiome can also be achieved by designing specific simple chemical compounds, which alter the chemical environment in the gut sufficiently to alter bacterial activity.
Fecal microbiota transplantation (FMT) is a physical approach that aims to restore microbiota dysbiosis that occurs commonly in patients with inflammatory bowel disease and metabolic diseases. There is a growing interest in using FMT in treating diseases beyond the gut [19]. Almost all attempts to modify the gut microbiome have used experimental animal models or been based on case studies. It is now time to modify the gut microbiome more systematically and robustly and assess its therapeutic potential in treating an increasing range of diseases.
9.1. Fecal Microbiota Transplantation
Fecal Microbiota Transplantation is a relatively recent approach to modify the gut microbiome. This approach consists of transferring the entire fecal microbial community, including bacteria, archaea, fungi, viruses, and metabolites, from healthy donors to people afflicted with a specific disease associated with a dysbiotic microbiota [20]. This entire microbial community has the potential to restore a diseased dysbiotic microbiota and reduce the symptoms associated with the disease. FMT represents a more complex biotherapy than simply administering probiotics, which transfer only a few microbial species, while FMT transfers the entire gut micro-ecology as a proper organ. Importantly, FMT appears to be highly safe, not triggering an immune response or rejection.
The fecal matter used in this approach must come from selected donors that undergo microbiological tests, clinical exams, and anthropometric evaluations to assess the psychiatric, metabolic, and immunological profiles. The collected fecal stools are then processed and prepared following specific procedures. The preparation includes homogenization, filtration, resuspension in sterile saline, and centrifugation. The final fecal microbiota suspension is stored at -80°C until the day of transplantation. There are two methods to introduce fecal microbial communities into the diseased recipient: the upper gastrointestinal tract (via an upper endoscopy or a nasogastric tube) or the lower gastrointestinal tract (via an enema or a colonoscopy). Specific consideration needs to be given to this transplantation method, as it can modify the success of FMT.
10. Future Directions in Gut Microbiome Research
The gut microbiome is a complex community of microorganisms that resides in the gastrointestinal (GI) tract and plays an indispensable role in maintaining host health. The intricate interplay between gut microbes and host physiology is intimately linked to a variety of health conditions such as obesity, diabetes, inflammatory bowel disease, and colorectal cancer. Scientifically understanding the gut microbial world has dramatically advanced in the past 20 years, primarily with the development of next-generation sequencing technology, big data analysis, and bioinformatics. The gut microbiome has been investigated extensively in many health and disease conditions, uncovering a plethora of interesting concepts about its composition and diversity. Efforts are also being made to advance knowledge regarding the microbiome and related metabolites and paracrine signals and to identify driver microbes, leading to the development of nutraceuticals, probiotics, and food additives that mitigate the negative impact of certain foods or gut constituencies on human health. Additionally, advances in technologies such as pasteurization, fermentation, microencapsulation, and blending aim to facilitate the delivery of multiple beneficial ingredients within a single product. These advances pose opportunities for revolutionizing food processing and nutrition science, thus maximizing the impact of food on health [18].
With the increasing advancement of sequencing technologies, bioinformatics, automated analysis tools, and novel interventions, it is time to envisage the future of gut microbiome research. In addition to understanding its role in health and nutrition research, focus is needed on exploring the microbiome world beyond the human gastrointestinal tract. Technological innovations might lead to the exploration of gut microbiota-host interactions at even higher spatiotemporal resolutions. These include mining well-characterized genomes retrieved from the gut microbiome to identify the recycling of indigestible nutrients via fundamental functional pathways and the decryption of metabolites affecting host genes and cellular pathways. Automation to implement rapid sample processing of small biomasses from environmental sources and running an analysis pipeline may render microbiomic studies feasible in poorly accessible locations or in require, such as industrial processes [21].
10.1. Technological Advancements
The gut microbiome is made up of trillions of microorganisms, including bacteria, fungi, and parasites. Advances in scientific research have revealed its profound impact on overall health, affecting areas such as nutrition, metabolism, immunity, and mood. Within the gut microbiome, nutrients play a crucial role in shaping microbial diversity, as food is the primary energy source for microbes and has both prebiotic and selective effects. For instance, dietary fibers provide food to beneficial microbes, while high-fat diets harm gut ecosystems [21]. Differences in gut microbiota diversity also account for the heterogeneity of individual responses to diet, a phenomenon known as precision nutrition. Understanding the intricate interplay between the gut microbiome and its surroundings allows researchers to design nutritional strategies to harmonize microbial communities and promote gut health.
Over the past decade, the exploration of the gut microbiome has made significant strides using advanced chemicals, bioinformatics, and sequencing technologies. New academic disciplines and fields, including microbiome-related precision and personalized health, are emerging, as evidenced by the establishment of research funding agencies focusing on the microbiome in the United States and Europe. A paradigm shift in research approaches from “observing” the microbiome to “engineering” it has begun [22]. This microbial revolution not only signifies the scientific progress in revealing the role of microbes in health and diseases but also represents a transformative shift in healthcare, opening new perspectives for prevention and treatment.
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