The Intestinal Microbiome in Humans: Its Role for a Healthy Life and in the Onset of Diseases

Abstract

The discovery of human microbiota shed a different perspective regarding human homeostasis and immune regulation. Gut microbiota comprises a multitude of microorganisms, its composition being host-specific and evolving throughout the lifetime, being subjected to both endogenous and exogenous factors. This subject gained significant interest after the improvement of metagenomic and metabolomic studies. The gut microbiome displays several roles, such as modulating gut permeability, digestive processes, metabolic pathways, and immune responses. Any dysregulation in the complex symbiosis mechanism between humans and the intestinal microbiome might lead to variable diseases. Environmental factors and diet play a very important role in maintaining a healthy gut microbiota. In this chapter, one aims to discuss the core microbiome of healthy subjects and how different stages of dysbiosis can play a role in the initiation and progression of pathogenic mechanisms leading to several diseases, such as gastrointestinal disorders (irritable bowel syndrome, inflammatory bowel diseases, infections or diarrhea associated with antibiotics, and colon cancer), metabolic disorders, obesity, diabetes, and allergies. We underline the importance of diet and environmental factors in modulating gut microorganism concentrations. We shed light on new possible perspectives regarding the modulation of gut microbiota for improving the health status of the host.

1. Introduction

Although the terms “microbiota” and “microbiome” are frequently used interchangeably, there are some distinctions between the two. The term “microbiota” refers to the live microorganisms found in specific environments, such as the gut and oral microbiota. The term “microbiome” refers to collecting all genomes within the microbiota, along with microbial structural elements, metabolites, and environmental conditions [1].

More than 100 trillion microorganisms, such as bacteria, yeast, and viruses, compose the human gut microbiota [2]. The gastrointestinal tract (GI) is considered to be the largest interface (250–400 m²) between the host, environmental factors, and antigens in the human body [2].

The composition of gut microbiota expands along the gastrointestinal tract, reaching its highest concentration at the colon level. This can be explained by the rare resistance of bacteria to the acidic medium or enzymes found in the stomach and proximal duodenum [3]. The bacterial density in the stomach is about 10 bacteria per gram, 10³ per gram in the duodenum, 10⁴ per gram in the jejunum, 10⁷ per gram in the ileum, and 10¹² per gram in the colon [4].

About 1000 bacterial species can be found in the colon, comprising approximately three million genes [5].

The bacteria that colonize the adult human gut are grouped into 7 major phyla: Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Euryarchaeota, Proteobacteria, and Verrucomicrobia. The dominant bacterial phyla are Firmicutes and Bacteroidetes, accounting for 90% of the gut microbiota [2, 6]. Moreover, the gut microbiome encodes over 100 times as many genes as the human genome [6]. The gut microbiome is often referred to as a “superorganism” due to its microbial diversity and its symbiotic relationship with the human body [7, 8]. In the last years, stool analysis techniques have facilitated researchers to analyze the components of the GI microbiota, with 16S ribosomal RNA gene sequencing being the most useful technique for describing gut microbial strains [6].

Gut bacteria is a key part of the digestion process. Commensal bacteria can extract and synthesize essential amino acids, vitamins, and short-chain fatty acids (SCFAs), helping digest dietary components that the human body alone cannot process, such as polysaccharides [9]. Intestinal bacteria also play a key role in maintaining immune and metabolic homeostasis and protecting the host against pathogen colonization [10].

Microorganisms interconnect with one another, having symbiotic reactions, generating various effects on population composition and activity within the gut microbiome. The interactions can be between microorganisms from the same species as well as from different ones. The interplay can be categorized as mutualism, synergism, commensalism, or, with a negative effect, amensalism (parasitism, antagonism, and competitiveness). Nevertheless, secondary metabolites are of high importance in maintaining a well-functioning ecosystem [1].

Colonic bacteria can digest complex carbohydrates and create metabolites like short-chain fatty acids (SCFAs) by producing enzymes that are active on carbohydrates [2]. Propionate, butyrate, and acetate are the three main SCFAs that are typically found in the gastrointestinal system in a ratio of 1:1:3 [2]. These SCFAs are swiftly absorbed by the enteral epithelial cells and are involved in the regulation of cellular processes such as gene expression, chemotaxis, differentiation, proliferation, and cellular death [2]. The gut microbiota is also implicated in the synthesis of essential vitamins, which the host is unable to manufacture [2]. Through its structural components and metabolites, the gut microbiota stimulates the host to produce various antimicrobial compounds [2]. These include AMPs like cathelicidins, C-type lectins, and prodefensins that are produced by the host Paneth cells via a pattern recognition receptor-mediated mechanism [2]. The other method through which the gut microbiota inhibits pathogen overgrowth is by inducing mucosal secretory immunoglobulin A [2].

The human microbiome is seen an essential therapeutic objective in the area of personalized medicine by providing fascinating therapeutic keys for a multitude of conditions. Its composition can be influenced by diet modulation, by adding prebiotics, probiotics, or synbiotics or by even taking into consideration microbiome transplants, of which fecal transplant is drawing more attention [1].

Intestinal microorganisms can influence the immune or metabolic pathways of several diseases, making the host vulnerable or immune to certain pathogens [2].

The relevance of a healthy gut microbiome can be reflected by the gut–brain, gut–lung, or even gut–liver axis, making the study in this field an increasingly alluring research topic [1].

There is growing evidence in the literature regarding the bidirectional connection between the human gut bacteria and the brain. The microbiota has effects on the central nervous system through neuroendocrine- and immune-mediated mechanisms, while the brain can act on the gut microbiota through the autonomic nervous system. SCFAs can modulate the intestinal barrier function, the secretion of mucosal neurotransmitters, the sympathetic nervous system, or the concentrations of neurotransmitters, such as GABA, serotonin, histamine, melatonin, and acetylcholine. Additionally, gut microbes can alter afferent sensory nerves by inhibiting calcium-dependent potassium channels. They can also have an impact on the role of immunity [3]. By regulation of gastrointestinal motility and mucus production and change of the intestinal permeability and immunological functions, the brain affects the gut microbiota [3].

This review aims to summarize our current understanding of the development of gut microbiota and the changes that arise during different stages and conditions.

2. The core microbiome of a healthy individual

The core microbiome refers to a set of stable components across populations. The taxa that compose the core microbiota must be present in most subjects in appreciable amounts [11]. However, both researchers and international projects strived for decades to define this set of components [12, 13]. The core microbiome comprises a group of strains that are transferred from the mother before birth and continue to evolve over the first few months of life based on the infant’s nutrition and environmental factors [14]. The ability of the core microbiome to resist changes brought on by perturbations and to return to an equilibrium state following concerns is one of its key characteristics [15]. This chapter aims to define the core microbiome and how it fluctuates across different age groups.

2.1 Early childhood development of the microbiome

There is conflicting evidence regarding whether or not the microbiome is influenced before birth by the microbial colonization of the placenta [16]. The presence of bacteria in the placenta, the amniotic cavity, the umbilical cord, and meconium has led some scientists to support the theory that infant gut colonization begins in utero [17, 18, 19, 20, 21, 22, 23, 24].

However, other studies agree that gut colonization starts at birth, and this microbial challenge leads to the development of the immune system [25]. Current data has demonstrated a significant increase in facultative anaerobes and obligate anaerobes after birth [26].

Studies suggest significant differences in intestinal microbial composition in infants born vaginally and infants delivered via C-section (Figure 1) [27].

Figure 1.

Factors contributing to the development of the microbiota in early life. Created with Biorender.com.

Vaginal delivery is associated with early colonization with microbes normally found in the vaginal tract, such as Lactobacillus, Prevotella, and Sneathia spp. [28]. The intestinal microbiome of infants born via C-section is influenced by bacteria typically found on the mother’s skin, oral microbiome bacteria originating from the mother’s stool, and even bacteria found on hospital surfaces [27, 29]. This leads to a flora dominated by Staphylococcus, Corynebacterium, and Propionibacterium [29]. Moreover, in the first months of life of infants born vaginally, there tends to be an increase in the proportion of Bifidobacteria and Bacteroides. In contrast, this proportion remains low in infants delivered via C-section [29, 30]. This is of great importance considering that both Bacteroides and Bifidobacteria are considered health-promoting bacteria [31]. On the other hand, increased numbers of potentially pathogenic, proinflammatory bacteria such as Klebsiella and Enterococcus seem to be present in the intestinal flora of children born by C-section [30, 32, 33]. In addition, studies have correlated these differences in the gut microbial composition with a predisposition to infections, allergies, and inflammatory diseases [28, 30, 34, 35].

Another factor that influences the gut microbiome development is the infant diet. Specifically, the intestinal microbiota of infants that are breast-fed is dominated by Lactobacillus, Staphylococcus, and Bifidobacterium. In contrast, the gut microbiome of formula-fed infants mainly consists of bacteria such as Roseburia, Clostridium, and Anaerosipes [16, 27, 36]. Interestingly, after breastfeeding cessation, the gut microbial composition rapidly swifts toward a composition closer to the adult microbial flora [27]. In preterm infants, delayed colonization and low diversity are representative for the intestinal microbiome. Moreover, some studies have shown that in preterm infants, the levels of potential pathogenic bacteria and facultative anaerobic bacteria are increased. In contrast, the levels of mandatory anaerobic bacteria seem to be decreased [37, 38, 39]. These differences in terms of microbial composition have been associated with several disorders such as gastrointestinal infections and necrotizing enterocolitis [40, 41].

In the first year of life, the infant’s gut microbiome matures and becomes more complex. This time period seems to depend on several environmental factors like antibiotic treatment, living with household pets, and growing up with siblings [36]. Antibiotic exposure leads to changes in the intestinal microbial population, such as a less diversity of the microbiota. It also increases the risk of allergies, asthma, and metabolic disorders [36, 42]. Between the ages of 1–3 years old, microbial diversity increases, and at 3 years old, it becomes more stable and resembles the composition of the adult gut microbiota [43].

2.2 The adult healthy microbiome diversity

The gut microbial community composition in adults is highly variable in the same individual and among individuals [44]. Microbial richness and diversity are characteristic of a healthy gut microbiome. The composition of the gut microbiome depends on age, sex, dietary habits, antibiotic use, physical activity, and weight.

Three bacterial phyla dominate the healthy adult gut microbiota, Firmicutes (Lachnospiraceae and Ruminococcaceae), Bacteroidetes (Bacteroidaceae, Prevotellaceae, and Rikenellaceae), and Actinobacteria (Bifidobacteriaceae and Coriobacteriaceae). The Firmicutes/Bacteroidetes (F/B) ratio plays a major role in maintaining homeostasis, and variations in this ratio have been correlated with several pathologies. An increased number of Firmicutes and a reduced population of Bacteroidetes have been observed in obese patients. In contrast, a decrease in the F/B ratio has been associated with the development of inflammatory bowel disease [45, 46].

The MetaHIT consortium proposed classifying the gut flora by enterotypes, Enterotype 1, characterized by a high abundance of Bacteroides; Enterotype 2, characterized by a high abundance of Prevotella; and Enterotype 3, which has a high concentration of Ruminococcus [47]. An enterotype represents a functional association of bacteria of different species with specific ways of generating energy from fermentable dietary components found in the colon [48]. Bacteria from enterotype 1 generate energy by degrading carbohydrates and proteins, and bacteria clusters of enterotypes 2 and 3 degrade mucin glycoproteins of the gut mucosal layer [48].

One of the challenges in defining a healthy microbiome comes from the fact that most studies on microbiome composition have included participants from socioeconomically developed countries from Europe and North America. The microbiomes of people from nonindustrialized and industrialized regions differ in composition, with a nonindustrialized microbiome being adapted to fiber degradation. In contrast, an industrialized microbiota is adapted for mucin degradation due to antibiotic and different drug exposure [49]. For example, the microbiota of Hadza hunter-gatherers of Tanzania is characterized by a greater phylogenetic and carbohydrate-active enzyme diversity than that of Western populations [50]. In addition, a study that compared the gut microbiota of 106 Japanese subjects with the gut microbiota of subjects from 11 different countries showed significant differences between the two groups. Namely, the Japanese gut microbiota is characterized by a higher abundance of the phylum Actinobacteria due to its high quantity of Bifidobacterium species, a remarkable depletion of the archaeon Methanobrevibacter smithii, and an overall depletion of genes responsible for methanogenesis and increased levels of anaerobic acetogens such as Blautia species. The Japanese gut microbiota also has a high carbohydrate metabolism capacity, which translates into higher levels of SCFAs and hydrogen end products, positively affecting host health [51].

Decreased microbial diversity has been correlated with several chronic illnesses, such as diabetes and obesity [52].

Increased diversity has been associated with longevity in some studies on Asian populations [53, 54]. Moreover, when comparing the gut microbiome of long-living Chinese patients to the microbiomes of a group of long-living Italians, it was demonstrated that although the groups differed in composition, diversity was the common characteristic. They also discovered that the long-living Chinese have higher concentrations of a particular bacterial genus, Clostridium cluster XIVa, which is renowned for producing SCFAs [52].

2.3 The microbiome in elderly and age-related dysbiosis

The gut microbiota changes substantially in diversity and microbial composition with age, especially in people over 70 years old [55]. Most of the elderly experience comorbidities associated with gut microbiota; thus, it is difficult to define the healthy gut microbiome in this age group.

The reduced microbial diversity and the differences in the gut microbial composition of the elderly compared to healthy adults have been attributed to lifestyle changes, dietary schedule, reduced mobility, weakened immune strength, decreased intestinal function, altered gut morphology and physiology, infections, and increased hospitalizations and medication [11, 52, 55, 56, 57, 58]. Reduced gut microbial diversity of the core microbial groups has been associated with increased frailty and reduced cognitive performance [59].

The gut microbiota of the elderly is generally characterized by reduced amounts of commensals like Bacteroides, Bifidobacteria, and Lactobacilli and increased amounts of opportunistic bacteria such as Clostridium perfingens, Clostridium difficile, and enterobacteria [11, 60, 61, 62, 63]. At a phylum level, the microbiota of elderly subjects is dominated by Bacteroidetes, while the microbiota of healthy adults is dominated by the Firmicutes phylum [55]. In addition, studies have demonstrated that increased levels of Proteobacteria are common in the microbiota of elderly and long-living subjects [54].

In addition, the microbiota of the elderly is characterized by a reduced metabolic capacity with lower SCFAs levels [64]. The lower levels of SCFAs are closely related to the so-called “inflamaging” process that appears in the intestine of aged people [65]. Compared to younger subjects, the intestinal bacterial metabolism shifts from predominantly saccharolytic to a predominantly putrefactive metabolism in older subjects. This might account for the changes in bacterial metabolism and the production of bacterial metabolites [66].

Numerous researchers have looked at the microbiota of centenarians to characterize the healthy microbiome of the elderly [53, 54, 58, 67]. This research set out to identify the distinctive features of the centenarian microbiome that enable them to adapt to the accumulating oxidative alterations and chronic inflammatory processes that define the extreme aging phenotype. These features are represented by increased diversity of microbial populations, and enriched populations of beneficial bacteria such as Akkermansia and Clostridium XIVa, known as SCFAs producers [53, 54]. Additionally, the microbiota of centenarians presents an increased abundance of facultative anaerobes such as Escherichia coli and a decrease in Faecalibacterium prausnitzii [68].

3. Dysbiosis, stages of dysbiosis, and disease onset

An individual in a healthy state possesses all bacterial phyla in a specific equilibrium, providing a colonization resistance for exogenous bacteria and preventing the overgrowth of potentially pathogenic bacteria. This state is called eubiosis. Any disruption in this equilibrium is known under the general term of dysbiosis. Dysbiosis occurs due to the loss of beneficial bacteria, which leads to the overgrowth of potentially pathogenic bacteria. The final result of these two evolving stages is the loss of bacterial diversity [69].

3.1 Shannon index and stages of dysbiosis

The Shannon Diversity Index (sometimes called the Shannon–Wiener Index or, erroneously, Shannon-Weaver Index) is used for measuring the diversity of species in a community. The Shannon index considers the percent of each species in an ecosystem [70].

Shannon index is also noted as H is calculated with a certain formula, using the proportion of the whole community, which is made up of species. The H value is proportional to the degree of diversity in a certain community. The index statistically depicts biodiversity regarding abundance, uniformity, and dominance. It can differentiate the degree of variation between populations with the same number of alleles. The loss of rare alternative forms easily influences Shannon index and provides more information than allelic abundance or an ordinary number of alleles [71].

The human gut has over 1000 bacterial species, both beneficial and harmful microorganisms. In physiological conditions, the interactions between gut microbiota and the host can maintain homeostasis and a normal commensal relationship, limiting the possible development of pathogenic bacteria [72].

Dysbiosis appears when homeostasis is altered. In this case, several changes occur: alteration of the bacterial composition of microbiota, modified bacterial metabolic activity, and abnormal distribution of bacteria in the gut. The three stages of dysbiosis are loss of beneficial organisms, excessive growth of potentially harmful microorganisms, and loss of overall microbial diversity. However, these three types usually occur simultaneously. Dysbiosis has several consequences on the host’s general health, even associated with obesity, diabetes, autism, inflammatory bowel disease, autoimmune conditions, neurological disorders, or neoplasia [72].

Levy et al. classified type types of dysbiosis: “bloom of pathobionts, loss of commensals, or loss of diversity” [69], while Vangay et al. described four types (“loss of keystone taxa, loss of diversity, shifts in metabolic capacity, or blooms of pathogens”) [73].

Dysbiosis is influenced by inflammation, infections, diet, xenobiotics, genetics, and environmental factors. An abnormally structured microbiota can affect innate and adaptive gut immunity. These immune pathways affect the colonization niche of gut microbiota by influencing antimicrobial peptides and IgA antibody secretion. Although dysbiosis is associated with many immune-related conditions, it is still needed to be determined if it is, indeed, a cause or a consequence of the disease [69].

3.2 Irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder affecting 11% of the global population, and it is defined by recurrent abdominal pain associated with stools of abnormal consistency or frequency, occurring for at least 6 months [74, 75]. According to the Bristol stool form scale, there are four clinical subtypes regarding the bowel habits of the patients: IBS-D (diarrhea-predominant IBS), IBS-C (constipation-predominant IBS), IBS-M (mixed IBS), and IBS-U (unsubtyped IBS) [76, 77].

Although the exact pathogenesis of IBS remains unclear, evidence suggests that gut microbiota could be an important tool in mediating this gastrointestinal disease [76, 78]. Studies showed that patients with IBS can have different bacterial composition and richness of the gut microbiota than healthy individuals. Some possible mechanisms involved in IBS pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, emotional distress, genetic alterations [79], and, most recently, gut microbial dysbiosis [80]. Dysbiosis is the term used to describe an unbalanced gut microbiota, frequently discovered in postinfectious IBS [81]. Consequently, dysbiosis can be considered an initiating factor of IBS [81].

The “microbiota–gut–brain” axis theory has been brought forth, confirming the critical part that microbial dysbiosis plays in the emergence of IBS symptoms [78, 82]. According to this theory, environmental variables change the gut microbiota in genetically predisposed people, compromising the integrity of the intestinal epithelial barrier [83]. Following the breach of the intestinal barrier, bacteria engage with the host’s immune system, set off a chain of immunological reactions, and cause low-grade mucosal inflammation in the gut wall [83]. Consequently, changes in sensitivity and motility appear, leading to the onset of IBS symptoms like abdominal pain, bloating, and changes in bowel habits [79].

The latest research by Su et al. on irritable bowel syndrome microbiota alterations revealed new data that could improve the future approach to treating and preventing this gastrointestinal disease [84]. The study showed a significant reduction in bacterial diversity of the gut microbiome in patients with IBS-D and IBS-U but not in those with IBS-C when compared to control groups. IBS-D subjects also suffered a decrease in bacteria richness compared to controls. IBS-D and IBS-U had similar compositional alterations, such as depletion of Firmicutes, Actinobacteriota, Verrucomicrobiota, and Campilobacterota and enrichment of Proteobacteria. Subjects with IBS-C showed different phylum abundance: Verrucomicrobiota and Desulfobacterota as pathogenic bacteria. Escherichia/Shigella were found to increase in all three IBS subtypes, but specifically in IBS-D, where they exhibited the strongest positive correlation with hydrogen sulfide production. Bacterial genera like Sutterella, Faecalibacterium, Bifidobacterium, Prevotella, or Ruminococcus showed decreased levels in all IBS patients [84].

The functional changes described in this study revealed that pathways related to palmitoleate biosynthesis were elevated in IBS-C. In contrast, LACTOSECAT pathway involved in the degradation of lactose and galactose was decreased in IBS-D and IBS-U but increased in IBS-C [84].

The data suggested that IBS patients with depression in all three subtypes had lower levels of Bifidobacterium, Sutterella, Butyricimonas, and Butyricicoccaceae UCG009. Compared to IBS patients without depression, higher levels of Proteus in the gut microbiota analysis and depletion of several pathways involving the production of SCFAs were identified [84]. SCFAs are known for inhibiting inflammatory reactions and malignant growth [80]. A growing body of research supports the relationship between microbial dysbiosis and the emergence of anxiety and depression. For instance, gamma-aminobutyric acid (GABA) is known to be produced by several species of the Lactobacillaceae and Bifidobacteraceae family of bacteria. The central nervous system’s primary inhibitory neurotransmitter, GABA, is crucial in the pathophysiology of mood disorders [85, 86]. Additionally, it has been discovered that bacteria from the genera Bacillus and Escherichia create additional neurotransmitters linked to mood and behavior, including dopamine, serotonin, and norepinephrine [87, 88].

Other studies focused on the importance of the serotonin system as a potential target for IBS treatment [89]. Serotonin synthesis from colonic enterochromaffin cells is encouraged by secondary bile acids and SCFAs, which are mostly generated by Eubacterium, Bacteroides, and Clostridium (clusters IV, XI, XIII, and XIVa) [85]. In addition to its other roles, serotonin is a crucial neurotransmitter that controls gastrointestinal motility [90]. IBS-D patients’ serum serotonin levels were found to be higher, and in IBS-C patients, the serum serotonin levels were lower [91].

The study by Su et al. also confirmed the preexisting data that young age and female gender determine more microbiome alterations in all three IBS subtypes [79, 84]. Nevertheless, the microbiota difference between IBS patients and controls decreased with age in the case of IBS-D and increased in the IBS-C subtype [84].

The dietary factors like alcohol, lactose, whole grain, eggs, red wine, or seafood were considered in the IBS patients microbiota study. The results showed that in all three IBS subtypes, subjects who took lactose daily or regularly (3–5 times per week) exhibited larger microbiome alterations than those who never had lactose intake. In contrast, those who drank red wine achieved the opposite effect [84].

3.3 Inflammatory bowel disease

Inflammatory bowel disease (IBD) is a multifactorial autoimmune intestinal disease comprising Crohn’s disease (CD) and ulcerative colitis (UC) [92]. UC is a long-lasting inflammatory and superficial ulcerative disease of the colon. In contrast, CD is a transmural disease of any part of the gastrointestinal tract, often associated with granuloma formation [92, 93, 94].

InBD has clinical periods of remission and relapse, with its onset at any age, but it is usually diagnosed between 20 and 40 years [95].

InBD’s cause is still unknown, although, in genetically predisposed people, it seems to be maintained by a weakened immune response to gut microbes [95]. This aberrant immunological response is linked to dysregulation of both innate and adaptive immune responses [95]. Specific intestinal epithelial barriers are breached in the case of InBD, and non-resolving mucosal damage is considered a key aspect of the illness [96]. Although the exact etiology is uncertain, it may be linked to an infectious pathogen [97], a chemical substance [98], or a metabolic change most likely caused by diet-mediated dysbiosis [99]. According to recent data, the loss of immunological tolerance caused by gut dysbiosis may cause or exacerbate inflammatory bowel disease [100].

Studies have clarified that the composition of the gut microbiota is different in patients with InBD versus healthy individuals and has its differences in patients with CD versus UC [101, 102]. In the gut microbiota of individuals with UC or CD, the abundance of Roseburia and Phascolarctobacterium was dramatically reduced, but Clostridium levels were elevated [103]. Compared to the InBD groups, the control group had a significantly higher concentration of microorganisms such as Gemmiger formicilis and those from the order Clostridiales [104]. Similarly, Ruminococcaceae family microbial organisms, specifically Ruminococcus species, showed noticeably higher prevalence in controls than in InBD [104]. On the contrary, the gut microbiota from patients with InBD was much more enriched in Blautia producta and Clostridium ramosum than that from the control group [104].

Cohort studies observed that the genus Coprococcus 2, Oxalobacter, and Ruminococcaceae UCG014 were associated with a higher risk of InBD. In contrast, genus Eubacterium ventriosum group and Enterorhabdus were associated with a lower risk of InBD [105]. Genus Coprococcus 2 and the Eubacterium ventriosum group were specifically causally related with UC, Lachnospiraceae UCG001, Ruminococcaceae UCG014, and Oxalobacter were specifically causally connected with CD, according to the analysis from Liu et al. [105]. Similar results have also been reported in mucus samples, where CD patients have a significantly higher abundance of aggressive bacteria, such as the genera Escherichia, Ruminococcus (R. gnavus), and Fusobacteria species, compared to healthy controls, and a significantly lower abundance of bacteria from the genera Faecalibacterium, Coprococcus, and Roseburia [106, 107, 108, 109].

In the past, studies utilizing fecal samples revealed dysbiosis in InBD, which is indicated by an overall reduction in the phylum Firmicutes (for example, Faecalibacterium, Roseburia, and Ruminococcus) and an increase in the phylum Proteobacteria (for example, Enterobacteriaceae) [107, 110, 111, 112]. These alterations in gut microbiota are more frequently encountered in the cases of CD than in those of UC [113].

Various digestive disorders lead to a depletion of F. prausnitzii. However, CD patients exhibit this depletion more frequently [104]. Similar microbial species decrease in CD patients as was confirmed by the investigation of Sankarasubramanian et al. [104]. It did, however, show a divergent abundance in the UC patients. Notably, F. prausnitzii also produces butyrate, an increase of which in UC patients may signify an adaptive advantage, as butyrate is a short-chain fatty acid that is necessary for intestinal epithelial cells to function properly [104].

3.4 Infections or diarrhea associated with antibiotics

Antibiotic administration is a major cause of dysbiosis, particularly a lowered microbial diversity [12, 114, 115].

The resistome is a group of antibiotic resistance genes (ARG) that coexists with the gut microbiome since early childhood [115, 116]. The multidrug-resistant bacteria, which show an increasing prevalence worldwide, are acquiring these ARGs, which helps them adapt to antibiotics [117]. ARGs are responsible for developing multidrug-resistant pathogens, especially after recurrent treatment with antibiotics in the first years of life [116]. Studies nowadays focus on understanding how the resistome interferes with the microbiome in different stages of life or in specific events like acute or chronic infections, as well as on how the quantity, identity, and function of ARGs could provide more perspective into new therapeutic management of the microbiome [115]. Research suggests that human gut resistome tends to enrich after antibiotic consumption. Still, its dimension is already notable even before intake, meaning that a transfer from environmental ARGs to host is happening even before exposure to antibiotic treatments [118].

Antibiotics can interfere with metabolic pathways and can decrease gut microbiome diversity [114, 119]. For instance, anaerobes that produce SCFAs may disappear due to antibiotic-induced alterations in the gut microbiota, which may also disturb the metabolism of carbohydrates and bile and cause an osmotic imbalance [120]. Following antibiotic intake, all three intestinal barriers are affected: the epithelial intestinal cells, the mucus and antimicrobial peptides layer, and the immunoprotective layer composed of different immune cells and various biomolecules. This event can interfere with the production of mucin, cytokines, and antimicrobial peptides, dysregulating intestinal function and leading to other infections or even causing recurrent episodes of infections [116].

Antibiotic-associated diarrhea (AAD) is a condition with a prevalence between 5 and70% in adults caused by overgrowth of pathogenic or opportunistic strains in the gut microbiome following antibiotic intake [116]. These microorganisms have each very different disease manifestations and affect specific mechanisms in the gut, but they are all linked to dysbiosis and structural damage of the intestinal wall [120].

Clostridoides difficile infection is the most common cause of nosocomial antibiotic-associated diarrhea in the adult population [121]. Risk factors include age over 65 years, long hospitalization in intensive care, and administering antibiotics (fluoroquinolones, clindamycin, cephalosporins, and beta-lactams in particular) or proton pump inhibitors [122, 123, 124, 125, 126, 127, 128].

Traveler’s diarrhea (TD) is defined as 3 or more liquid stools over 24 hours in patients traveling and has three degrees of disease severity. Mild TD characterizes as 3 unformed stools without other symptoms and does not interfere with the ability of the travelers to continue their activity. In the case of moderate TD, patients suffer from 3 to 5 or more unformed stools a day, without other symptoms, compared to severe TD that consists of more than 5 stools in 24 hours associated with abdominal cramps, fever, vomiting, tenesmus, or blood in feces [129].

Bacteria, viruses, protozoa, and fungi can all cause TD. In addition, enteroaggregative E. coli, other E. coli pathotypes, noroviruses, rotaviruses, Salmonella spp., Campylobacter jejuni, and Shigella spp. could also be responsible for TD. Recent papers have suggested that enteropathogenic E. coli and enteroaggregative E. coli are more common than enterotoxigenic E. coli—producing heat-labile or heat-stable toxin, which was previously thought to be the most frequent cause of TD [129].

Studies regarding the alterations in the diversity and composition of gut microbiota after antibiotic consumption confirm that F/B radio and Enterococcus levels increase [130]. Consequently, diet and food supplements like probiotics or prebiotics can improve gut health by restoring the balance between the species forming the intestinal microbiome [131].

3.5 Colon cancer

Colorectal cancer (CRC) is one of the most frequent cancers, and it carries a major health burden around the globe. It is the third most frequent cancer worldwide and the second in mortality among all cancers [76]. As it is with the majority of cancers, tumor formation in the colon depends on both genetic and environmental factors. Recent studies have suggested that the microbiota is an important environmental factor for some cancers, and it might play an important role in oncogenesis [132].

The theory that microorganisms might be involved in carcinogenesis has been demonstrated as early as the early sixties, using carcinogens in germ-free and conventional mice [133]. Human studies have shown that dysbiosis is also present in the microbiota of CRC patients and that there are metagenomic differences between the gut microbiota of patients diagnosed with CRC and that of healthy subjects. These studies have shown that compared to controls, the microbiota of CRC patients presented reduced microbial diversity, a higher richness in genes, increased amounts of procarcinogenic bacterial taxa (Bacteroides, Escherichia, Fusobacterium, and Porphyromonas) and reduced numbers of health-promoting taxa (e.g., Roseburia) [134, 135, 136, 137]. Apart from Fusobacterium nucleatum, whose connection with CRC has been extensively described, studies have identified other strains of bacteria to be enriched in CRC microbiota, including Porphyromonas asaccharolytica, Poststreprococcus stomatis, Parvimonas micra, and Solobacterium moorei [134, 137, 138, 139, 140, 141, 142, 143]. Other specific bacteria, such as Bacteroides fragilis, E. coli, Enterococcus faecalis, and Streptococcus gallolyticus, have also been associated with CRC in several studies [144, 145, 146].

Conversely, several health-promoting bacteria appear to be depleted in CRC microbiota, such as Streptococcus termophilus and the butyrate-producing genus Roseburia and other butyrate-producing bacteria like Lachnospiraceae and Ruminococcaceae [147, 148, 149, 150].

It appears that certain bacteria not only are pro-oncogenic but also have the capacity to remodel the gut microbiota to promote CRC progression [140].

The mechanisms by which these pro-oncogenic bacteria promote tumorigenesis and cancer progression include the production of genotoxins, inflammation, and immune regulation [147]. The relationship between chronic inflammation and cancer has been established and intensively described. Inflammation leads to mutagenesis and accumulation of mutations Tp53 and other genes in the intestinal epithelial cells [151]. Chronic inflammation of the intestinal epithelial cells reduces the barrier function and exposes stem cells to genotoxins [151]. The link between inflammation and cancer is well exemplified by the increased risk patients with InBD have for developing CRC [152]. Interestingly, studies on colitis mouse modes have demonstrated that cancer did not originate in germ-free mice or in mice treated with antibiotics, underlying the microbiota’s important role in colitis-associated cancer [153, 154]. The pro-oncogenic bacterium Fusobacterium nucleatum promotes intestinal tumorigenesis by activating the nuclear factor-κB (NF-κB) pathway and recruiting tumor-infiltrating myeloid cells, as demonstrated in Apc(Min/+) mouse models [155]. Furthermore, enterotoxigenic Bacteroides fragilis secretes Bacteroides fragilis toxin through which it can induce cancer formation in colonic epithelial cells by activating the inflammatory cascade involving IL-17 signal transducer and activator of transcription 3 and NF-κB signaling [150].

Another carcinogenic mechanism that involves the gut microbiota is represented by the production of genotoxins that further damage the DNA and lead to tumor formation. For example, E. coli secretes colibactin via the pks genomic island, a toxin capable of causing DNA damage, inducing genomic alterations and promoting genomic instability [156]. A second genotoxin that can induce DNA damage is the cytolethal distending toxin produced by pathogenic E. coli strains and Campylobacter spp., as studies have demonstrated [157, 158].

The major role the gut microbiota plays in the development and progression of CRC underlines the importance of further studies that focus on modulating the microbiota to prevent CRC and improve treatment outcomes. Secondly, understanding the changes in the CRC microenvironment can help select microbial biomarkers useful in early diagnosis and treatment evaluation.

3.6 Metabolic syndrome

Metabolic syndrome (MetS) has an alarming increasing prevalence around the world. Its complications are cardiovascular and can also concern nonalcoholic fatty liver or obstructive sleep apnea [5]. The pathophysiology behind MetS comprises a perpetual state of chronic inflammation, insulin resistance, autonomic system dysfunction, and oxidative stress [159, 160].

The term was first used in 1970, but in 1988, Gerald Reaven changed the name of MetS to “syndrome X,” adding insulin resistance to the concept [161]. Over the years, several attempts were made to define the MetS. It is now known that it comprises central obesity, hyperglycemia, dyslipidemia, and arterial hypertension, but more attention is lately drawn to gut microbiome [162].

An important, rather newly, investigated risk factor for MetS is the imbalance in the gut microbiota composition, with significant structural differences compared to the healthy subjects. The pathophysiological chain in MetS involves low-grade inflammation, alteration of the intestinal barrier, and production of metabolites that alter the metabolism and hormone synthesis, leading to a continuous cycle that further only favors MetS [5].

In patients with MetS and high levels of gamma-glutamyl transpeptidase (GGT) versus those with only MetS, with normal levels of GGT, the gut microbial composition was significantly different, noting the presence of unfavorable bacteria in higher concentrations (Megamonas hypermegale, Megamonas funiformis, Klebsiella pneumoniae, and Fusobacterium mortiferum) and low concentrations of “good” bacteria, such as Faecalibacterium prausnitzii, Eubacterium eligens, Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bacteroides dorei, and Alistipes putredinis [163].

3.7 Obesity

Due to the expanding western lifestyle, obesity rates among young individuals are expanding. The gut microbiota of obese individuals is significantly different from that of healthy ones. For instance, a study on animals fed with high-fat diets revealed high levels of Firmicutes, Proteobacteria, and Verrucomicrobia phylum and low levels of Bacteroidetes. It was reported that these changes were reversed after the cessation of a high-fat diet [164].

Overweight subjects possess an augmented F/B ratio when compared to normal-weight subjects. Firmicutes bacteria can digest long-chain carbohydrates, generating significant amounts of nutrients, and higher energy uptake, favoring weight gain and obesity [165, 166]. The microbiota of obese subjects can store more energy from diet compared to normal-weight controls [167].

Low levels of Ruminococcaceae and Clostridia were noted in obese subjects [168, 169]. Consistent data showed a high abundance of Bacilli and its families Streptococcaceae and Lactobacillaceae and diminished accumulations of Clostridia (Christensenellaceae, Clostridiaceae, and Dehalobacteriaceae) [169].

Operational taxonomic units belonging to the Firmicutes phylum had the most significant associations with adipose tissue. Still, one must keep in mind that Firmicutes, however, is the phylum that dominates the human gut. Interestingly, Oscillospora, Lachnospira, and Ruminococcus operational taxonomic units suggested a protective cardiovascular role, negatively associated with visceral fat mass, while Blautia operational taxonomic units proved the opposite [170]. Blautia genus was noticed as a risk factor, being positively associated with visceral fat [168].

A randomized, double-blind, placebo-controlled trial that concerned daily oral administration of Akkermansia muciniphila for 3 months in obese or overweight individuals led to enhanced insulin sensitivity and lower levels of insulin and total plasma cholesterol [171].

In animal subjects with high-fat diets, oligofructose influenced appetite and body weight by controlling the production of gut peptides. Metabolites resulting from fiber fermentation lead to the production of endogenous glucagon-like peptides 1 and 2 (GLP1, GLP2), GLP1 providing beneficial effects on glucose metabolism. At the same time, GLP2 is involved in the stability of epithelial tight junctions [172, 173].

3.8 Diabetes

Either elevated fasting glucose or type 2 diabetes mellitus (T2DM) belongs to MetS. Chronic inflammation is linked to obesity and insulin resistance. However, not only type 2 diabetes but also type 1 diabetes is influenced by the gut microbiome [174].

The major source of energy for the gut microflora is carbohydrates. T2DM patients usually consume less fiber, dietary fiber being associated with high microbial diversity [175]. Fiber consumption is responsible for a stable microflora [176], favors the fermentation of gut microbes, and amplifies the production of SCFAs. This is essential in host metabolism since SCFAs are in glucose homeostasis [177].

The gut microbiota of subjects with T2DM is characterized by a certain degree of dysbiosis [5]. The gut microbiota in T2DM is mainly composed of Bacteroides, Faecalibacterium, Akkermansia, Ruminococcus, and Fusobacterium, with lower levels of Roseburia [178].

At the debut of T2DM, some evidence suggests the rich presence of Bacteroidetes and diminished populations of Firmicutes [179].

In T2DM patients, gut microbiota is significantly lower in Firmicutes, but nevertheless, it is rich in Gram-negative bacteria belonging to Proteobacteria and Bacteroidetes [180]. The Bacteroidetes/Firmicutes and Bacteroides-Prevotella/C. coccoides-Eubacterium rectale ratios were higher in T2DM patients and positively correlated with glycemic levels [180, 181]. Excessive populations of Actinobacteria and Bacteroidetes phyla can be found in T2DM subjects [182]. However, evidence suggests that reduced concentrations of Lactobacillaceae are associated with GLP1 resistance [183].

However, it is worth mentioning that low levels of Bifidobacteria and F/B ratio were noted in type 1 diabetes [182]. In T2DM, there are lower levels of butyrate-producing bacteria, such as Bifidobacterium, Akkermansia, and Faecalibacterium and also diminished concentrations of the Firmicutes phylum, Clostridiaceae, and Peptostreptococcaceaea families [182].

Butyrate, a short-chain fatty acid, is an important result of dietary fiber fermentation in the gut. It is energy fuel for intestinal epithelial cells; it can favor satiety, lower inflammation, oncogenesis, and oxidative stress and enhance gut barrier function. Furthermore, butyrate has a role in the defense against obesity and insulin resistance [184]. Butyrate is also important in diabetes since it promotes the normal function of pancreatic beta cells [185].

Higher concentrations of proinflammatory bacteria, such as Escherichia coli, and lower concentrations of antiinflammatory bacteria, such as Faecalibacterium prausnitzii, were noted in T2DM [186, 187].

In T2DM, SCFA production is affected, being influenced by low Faecalibacterium prausnitzii concentrations [187]. Altered production or absorption of propionate was mentioned to elevate the risk for T2DM [188].

Lipopolysaccharides are secreted by Gram-negative gut bacteria, leading to low-grade inflammation by acting on type 4 toll-like receptors, amplifying the likelihood of insulin resistance [189].

3.9 Autoimmune conditions and allergies

An unbalanced immune system, which loses its ability to distinguish self from nonself antigens accurately, is involved in autoimmune diseases. The human gut microbiota plays an essential role since it can maintain the homeostasis of the immune system. It is involved in gut functional integrity, barrier stability, and permeability, determining immune response and the progression of inflammatory conditions [190].

Autoimmune conditions involve excessive or improper production of autoantibodies. Immunity can be altered by either genetic or environmental factors. There is growing evidence that gut microbiota can be applied in autoimmune diseases. The modulations of host immune response through antigen-presenting cells may bring forth antigen presentation and cytokine secretion, influencing the differentiation of T cells and leading to an altered balance between T helper 17 and T regulatory cells. As a result, self and nonself antigen similarity and activated pathogen-derived autoreactive T and B cells generate and promote autoimmunity. Moreover, the gut permeability is modified since the expression of tight junction proteins is altered. Weakened gut barrier integrity is important in the pathophysiology of autoimmunity because this way, the immune system interacts with commensal intestinal bacteria [190].

T helper 17 cell activation can be determined by gut microbiota, such as Enterococcus gallinarum and Bifidobacterium adolescentis [191, 192, 193].

Unfortunately, the incidence of allergic reactions has continually expanded over the past years, especially in developed countries. The pathogenesis is complex, including genetic, epigenetic, and environmental factors. Recently, gut microbiota has become an interesting topic in these afflictions [194].

The most common allergens are represented by pollens, dust, insect bites, foods, and drugs resulting in rhinitis, eczema, asthma, or even more severe reactions leading to anaphylactic shock [195].

The gut microbiota plays a major role in immunity, regulating the tendencies of immune reactions, type 2 immunity, and basophil hematopoiesis and preserving the gut barrier function [196].

Neutral bacteria can transform from probiotics to pathogenic bacteria, influenced by the environment or the health status [196].

SCFAs can modulate local gut FOXP3+ regulatory T cells, influencing immune homeostasis [197].

Food allergies are debated worldwide, with the exact cause still uncertain. There is no clear bacterial profile linked to food allergies. However, some evidence suggests that milk allergy in children with abundant Clostridia and Firmicutes after birth disappeared after some time [198].

The gut microbiota of children allergic to milk was rich in Lachnospiraceae and Ruminococcaceae, according to Canani et al. [199]. In young children with food sensitization to at least one nutriment, Haemophilus, Dialister, Clostridium, and Dorea genera were diminished. In contrast, Citrobacter, Oscillospira, Lactococcus, and Dorea genera were also reduced but strongly associated with food allergies [200].

In egg allergy kids, there was a decrease in Leuconostocaceae families and an increase in Streptococcaceae and Lachnospiraceae genera [199, 201].

Respiratory allergies (allergic rhinitis, and asthma) can also be connected to gut dysbiosis [199].

It was also underlined that dietary fiber intake amplified the concentrations of Bacteroidetes and Actinobacteria and lowered Firmicutes and Proteobacteria, diminishing allergic symptoms in allergic rhinitis [202].

Ege and collaborators evaluated almost 500 children in rural and urban Germany, indicating that concentrations of Acinetobacter, Lactobacillus, and Staphylococcus were inversely correlated with asthma and hay fever [203].

Administration of Bifidobacterium longum IM55 and Lactobacillus plantarum IM76 in animal subjects lowered seric IgE concentrations and interleukin 4 and 5 in the upper respiratory tract [204].

Bifidobacterium breve and nondigestible oligosaccharides inhibited inflammation in the lower respiratory tract of murine models by influencing T cell response [205].

In allergic asthmatic children, low Faecalibacterium prausnitzii and Akkermansia muciniphila were observed. It was suggested that these bacteria could promote the production of anti-inflammatory cytokines (interleukin 10) and prevent the release of proinflammatory cytokines (interleukin 12), thus inhibiting inflammation [205].

Atopic dermatitis is an inflammatory condition characterized by pruritus and eczematous lesions, estimating people of all ages, although predominantly children. The scarcity of Bifidobacterium, Akkermansia, and Faecalibacterium was noted in kids prone to asthma and atopic dermatitis [206].

The gut microbiome of children with atopic dermatitis has an inversely correlated diversity with butyrate-producing bacteria concentrations. It is also characterized by an abundance of Clostridia and low levels of Coprococcus eutactus (butyrate producer) [207].

In what concerns nickel allergy, the administration of probiotic Lactobacillus reuteri strains diminished gastrointestinal and cutaneous manifestations [208]. At the same time, another study pointed out the improvement of nickel sensitivity and ameliorated gut dysbiosis after Lactobacilli or Bifidobacteria administration [209].

4. Diet and environment in modulating the intestinal microbiome

To better understand the systemic connections linking the microbiota to human health, many researchers have resorted to studying the impact of dietary components on the microbiota [210]. Host nutrition is a recognized predictor of gut microbiota dynamics and function [211].

Different nutritional ingredients can change the human gut microbiota extremely quickly and in various ways, resulting in shifts in the population of microorganisms found in the digestive tract. Diet, including the consumption of prebiotics and probiotics, has a significant impact on both the gut microbiome’s composition and the intestinal barrier’s function, as noted in the review by Tamang et al. [212]. Probiotics are defined as live microorganisms that, when administered in adequate amounts, will confer a health benefit on the host (according to WHO). At the same time, prebiotics represent a group of biological nutrients that can be processed by the gastrointestinal microorganisms to produce beneficial SCFAs [213, 214].

Several studies compared the Mediterranean diet (MD) to the high-fat Western diet (WD) and found, firstly, that subjects who ate an MD, rich in healthy bioactive compounds, polysaccharides and polyphenols, had a higher gut microbiota diversity than those who ate a WD and, secondly, that more SCFAs are produced in the case of MD, while WD subjects showed increased risk of metabolic disease, such as obesity and hyperlipidemia [215, 216, 217, 218, 219, 220, 221, 222].

Studies suggest that a prolonged high-fat diet can increase the abundance of Ruminococcus, Dorea, Coprococcus, and Adercreutzia and decrease Anaeroplase and Turicibacter. These changes in the gut microbiota were also associated with obesity and insulin resistance [223].

Polyphenols found in tea leaves showed great results in inhibiting the growth of harmful bacteria in the gut, like Enterobacteriaceae or Bilophila, while enhancing the number of Bacteroides and Bifidobacterium and also promoting the production of SCFAs, which are beneficial for health [224, 225, 226].

Other dietary compounds, like polysaccharides, found, for instance, in the purple potato, can modulate the gut microbiota by increasing the population of Oscillospira and Lachnospiraceae while decreasing Suttella, a harmful bacteria [227]. The microbiota has carbohydrate-active enzymes that can digest polysaccharides, use their metabolites for energy production, and maintain health [228, 229].

Dietary carotenoids administration can modulate the gut microbiota by inhibiting the growth of harmful bacteria like Proteobacteria, Dialister, or Enterobacter and increasing the abundance of Bifidobacterium and, in high doses, raising the number of Lactobacillus strains [230]. Carotenoids are natural pigments that can be found in fruits and vegetables, but they can also be consumed in food or beverages colored with the help of carotenoids or even just as supplements [230, 231].

Nevertheless, microbiome-targeted nutritional interventions with measurable impacts on the microbiome remain elusive due to the microbiome’s highly individualized character and diet [212, 232].

As past studies have shown, physical exercise can also interfere with gut microbiome diversity. Sustaining physical activity determined the increase in Bacteroidetes and a decrease in Firmicutes in the intestinal microbiome, as well as promoted the production of SCFAs, which further enhance the body’s metabolism [233, 234, 235, 236].

Other studies suggested that sedentary individuals have a reduced gut microbiota diversity, which can lead to a wide range of health problems [237, 238]. These conclusions offer new approaches to managing and preventing metabolic disorders, stating that early planning of a proper diet and moderate exercise can reduce the burden on the health system [239].

5. Future perspectives

The hope for the future is to reach a time when personalized microbiome medicine can change how we treat specific diseases, when targeted agents can be used against particular microbiome constituents, with minimal side effects and great results (Figure 2) [115].

Figure 2.

Modulation of gut microbiota. Interventions are supposed to be a combination of dietary lifestyle and additional therapeutic measures. Created with Biorender.com.

The genetic manipulation of barrier protein function in animal models through dietary interventions, including the consumption of probiotics, to establish the causal association between gut microbiome changes and epithelial permeability is a provocative but promising subject [212].

The genetic manipulation of gut bacteria can facilitate a deeper molecular understanding of the interrelation between the microbiome and the host. It can even broaden the treatment options for metabolism alterations and associated conditions [240, 241].

Gut microbiota can serve as a new treatment target for metabolic syndrome. Further research is needed to enforce the necessary measures for the treatment and even prevention of one of the increasingly frequent pathologies of the century.

6. Summary

The authors’ goal in this chapter is to highlight the many methods for modifying gut microbiota in relation to various illnesses. The gut microbiota’s function in the human body is explained in great detail, along with the phyla that make up this “superorganism” as a whole. The unique changes the gut microbiota experiences throughout life, from infancy to adulthood and beyond in elderly adults, are shown in a timeline. This page focuses on dysbiosis, which is the dysregulation of the diversity of species and the proliferation of harmful microorganisms. Studies on various diseases have looked at the function of dysbiosis and its consequences on the development of pathogenic conditions. Understanding the stages of dysbiosis development in the body is made easier by the Shannon index’s explanation and its role in the variety of the microbiota population. In relation to the development and therapy of gut dysbiosis, diseases including irritable bowel syndrome, inflammatory bowel syndrome, colon cancer, infections, or diarrhea linked to antibiotics are examined. Obesity, autoimmune diseases, allergies, and metabolic syndrome are a few more illnesses that offer insight into the systemic effects of gut microbiota imbalance in the body. The authors also concentrated on disseminating knowledge regarding dietary interventions that can control the microbiota, a topic that is very hot and constantly evolving in this particular field. Environmental variables were also considered as potential contributors to the changes that may harm the microbiome.

The importance of a C-section versus a regular delivery as a factor in altering the composition of the gut microbiota was covered by the authors in the second chapter. The infant’s diet, including whether or not it was breastfed, is another significant element that is taken into account quickly. The pertinent findings were made when babies who stopped being breastfed had a microbiota that was similar to that of adults. Preterm or C-section babies were discovered to have more pathogenic bacteria in their guts and to be more prone to gastrointestinal infections or inflammatory illnesses in the future. Later, up until the age of three, babies have a tendency to acquire a gut microbe composition that is more stable and similar to that of an adult, being similar. However, a number of circumstances, like exposure to antibiotics, having pets around, or growing up with siblings, influence this process. The authors then went on to discuss the various theories surrounding a healthy adult gut microbiome, bringing to light some assessment tools, like diversity, which are directly tied to the microbiota’s state of health. The differences in the geriatric microbiota are another topic covered in the second chapter of this publication. The capacity of adaptation and evolution of the intestinal microbiota throughout life is emphasized, the microbial diversity decreasing with advancing age and changing dietary habits.

The third chapter examines dysbiosis from two angles: as a process that is explained in all of its stages and defined using the Shannon Index and as a contributor to numerous illnesses. The first pathology discussed that is thought to be influenced by dysbiosis is irritable bowel syndrome (IBS). The notion of the microbiota–gut–brain axis was highlighted as a crucial element in the emergence of microbial dysbiosis. In this thorough assessment of the literature, specific information about microbial changes in the gut flora as well as IBS symptoms were presented. In order to discover the impact on serotonin metabolism, specific focus was given to the changes in microbiota diversity for persons with IBS because psychological alterations like anxiety or depression were associated with the condition. Both ulcerative colitis and Crohn disease were taken into account while discussing inflammatory bowel illnesses in an effort to establish connections between dysregulations of the gut microbiota and particular strains of bacteria that are predominant in each of the cases in question. Another repercussion of dysbiosis is diarrhea brought on by antibiotic treatment. Researchers are accusing the mechanism through which antibiotics influence the host as the origin of microbial dysregulation. Additionally, several types of diarrheas are mentioned, including infection with Clostridium difficile and traveler’s diarrhea, both of which are distinct conditions than antibiotic-related diarrhea but are intricately related to one another. The authors emphasize that numerous bacteria can be pro-oncogenic and contribute to the development of the disease when they proliferate to abnormal levels that favor tumor genesis as they move on in their discussion of colorectal cancer from the point of dysbiosis. Understanding the changes in the gut microbiota of patients with colorectal cancer may result in groundbreaking findings in the area of the microbial-level therapeutic options for cancer that may improve classic therapies. The researchers also focused on metabolic conditions including obesity, diabetes, and even metabolic syndrome that might result from dysbiosis. Each pathology’s altered mechanisms or the most significant changes to the gut microbiota composition are described, and the differences between them are outlined. In this chapter, along with autoimmune diseases, allergies are also covered as a topic that is of recent interest. The importance of dietary components or specific diets in altering the gut flora is covered in the fourth chapter. Probiotics are described as a dietary therapeutic agent that significantly reduces dysbiosis. The relationship between exercise and a healthy bacterial population in the human gut was brought up once more at this point. On this note, according to the authors, following intestinal dysbiosis, sedentary people are more prone to infections and metabolic diseases.

The purpose of this review is to highlight the importance of research on the topic of dysbiosis and to provide insight into the mechanisms of several disorders that may be associated with the gut microbiome dysregulation, in addition to highlighting the need for customized microbiome therapeutics in the future.

Conflict of interest

The authors declare no conflict of interest.

Acronyms and abbreviations

AAD	antibiotic-associated diarrhea
ARG	antibiotic resistance genes
CD	Chron’s disease
CRC	colorectal cancer
F/B	Firmicutes/Bacteroidetes
GABA	gamma-aminobutyric acid
GGT	gamma-glutamyl transpepidase
GI	gastrointestinal
GLP 1, 2	glucagon-like peptides 1 and 2
IBS	irritable bowel syndrome
InBD	inflammatory bowel disease
MD	Mediterranean diet
MetS	metabolic syndrome
SCFAs	short-chain fatty acids
T2DM	type 2 diabetes mellitus
TD	traveler’s diarrhea
UC	ulcerative colitis
WD	Western diet