Introduction
The term intestinal microbiota, or popularly, intestinal flora, defines the totality of symbiotic, commensal or pathogenic microorganisms that live in the human intestine.
The microbiota is described as a vital organ with multidirectional axes to other organs, which ensures the host-microorganism interaction and which is in constant communication with endocrine, neuronal, humoral, immunological and metabolic pathways. This is why imbalances in the microbiota are linked to numerous conditions such as anxiety, depression, cardiovascular diseases, hypertension, obesity, diabetes, irritable bowel syndrome and cancer.
In the following, we aim to describe some of the general characteristics of the intestinal microbiota and how it is involved in maintaining the health of the body.
Gut Microbiota: An Overview
The gut microbiota is a conglomerate of microorganisms (mostly non-pathogenic), including bacteria, viruses, fungi and protozoa, that coexist in the human gastrointestinal tract. This microbial community is extremely diverse, numbering approximately 100 trillion microorganisms, which far exceeds the total number of human cells in the body. Its diversity is influenced by numerous factors, including the host's genetic information, age, diet, lifestyle and environmental exposure. The diversity of the gut microbiota is a key indicator of general and intestinal health. This diversity reflects the adaptability of the microbiota to the specific conditions of the intestinal environment and the metabolic needs of the host.
Composition and Diversity of the Gut Microbiota
The gut microbiota represents a complex and diverse ecosystem, dominated mainly by two bacterial phyla, Firmicutes and Bacteroidetes , which account for more than 90% of all gut bacteria. These two large groups are accompanied by other important phyla, such as Actinobacteria and Proteobacteria , each of which has specific roles and contributes to the overall functionality of the microbiota.
Firmicutes and Bacteroidetes are not only the most abundant but also the most studied phyla in the gut microbiota. Due to their abundance, the Firmicutes : Bacteroidetes ratio is an indicator of intestinal homeostasis, dysbiosis, metabolic diseases such as diabetes and obesity, non-alcoholic fatty liver disease, or increased levels of inflammatory markers (interleukin-6). The Firmicutes group includes a variety of bacterial genera, such as Lactobacillus , Clostridium , and Bacillus , which are involved in important metabolic processes, including the fermentation of dietary fiber and the production of short-chain fatty acids. On the other hand, the Bacteroidetes , with genera such as Bacteroides and Prevotella , are essential for the breakdown of complex polysaccharides and lipid metabolism.
Actinobacteria , another important phylum, includes the genus Bifidobacterium , known for its probiotic properties and role in maintaining intestinal health. Proteobacteria , although representing a smaller proportion of the intestinal microbiota, include important species that can influence host health, some of which have pathogenic potential.
An important role for the health of the whole organism is played by bacteria producing short-chain fatty acids. These acids, acetic, butyric and propionic, are synthesized by bacteria through the degradation of dietary fibers and have a regulatory role in lipid, cholesterol and glucose metabolism, anti-inflammatory, in shaping the immune response and maintaining the integrity of the intestinal barrier. While the synthesis of acetate is carried out by several types of bacteria, that of propionate and butyrate is carried out only by certain groups. Thus, propionate is synthesized by Bacteroidetes , Negativicutes and Lachnospiraceae while for butyrate it is carried out by F aecalibacterium prausnitzii, Eubacterium rectale and Eubacterium hallii.
The balance between different bacterial phyla and species is also crucial for the optimal functioning of the microbiota. Imbalances in this composition, known as dysbiosis, can contribute to the development of a wide range of conditions, including inflammatory bowel disease, irritable bowel syndrome, obesity, diabetes, and even neurological disorders. Thus, maintaining a healthy balance within the gut microbiota is essential for the overall health of the body.
The composition and diversity of the gut microbiota are fundamental elements that contribute to maintaining health and preventing disease. A detailed understanding of these aspects provides a solid basis for developing personalized therapeutic strategies and optimizing gut and overall health.
The Role of Microbiota in Gut Health
One of the primary roles of the microbiota is to break down and metabolize nutrients that cannot be efficiently processed by human digestive enzymes. In terms of metabolic efficiency, the microbiota maximizes the caloric availability of ingested nutrients by extracting calories from indigestible oligosaccharides and by modulating the absorptive capacity of the intestinal epithelium for essential nutrients and minerals.
The microbiota also has a protective role by adhering to the intestinal mucosa and avoiding potential pathogens, by secreting antimicrobial peptides (bacteriocins) as well as by interacting with various components of the intestinal barrier and the immune response. Disruption of this symbiotic balance can be due to the use of antibiotics and can lead to the appearance of enteric pathogens such as Clostrium difficile .
Another role of the intestinal microbiota is trophic, through its modulatory and stimulatory effect on the proliferation of intestinal epithelial cells, its interaction with neuroendocrine pathways and its influence on the homeostatic regulation of the immune system.
Gastrointestinal disorders such as acute diarrhea, irritable bowel syndrome, and inflammatory bowel disease are linked to altered gut microbiota. Malabsorption syndromes have also been linked to the presence of excess colonic flora in the small intestine. Other research suggests that gut bacteria may initiate colon cancer by producing carcinogens.
The decrease in the number of lactobacilli and bifidobacteria in parallel with the increase in the number of enterobacteria, coliforms, bacteroids and firmicutes represent changes in the microbiota characteristic of irritable bowel syndrome. There are hypotheses that, for this condition, link an abnormal composition of the microbiota to the activation of the adaptive immune response, alteration of epithelial permeability and the enteric nervous system.
Another crucial aspect of the role of the microbiota is supporting the intestinal barrier. The microbiota contributes to the formation of a protective mucus layer and to maintaining the integrity of tight junctions between epithelial cells, thus preventing the entry of pathogens and harmful substances into the systemic circulation. In this way, the microbiota plays a key role in preventing bacterial translocation and systemic inflammation.
Inflammatory bowel diseases are considered to be the result of the interaction between the host (organism) and microorganisms including intestinal microbial factors, an abnormal immune response, and a damaged intestinal mucosal barrier. Imbalance in microbiota homeostasis leads to colonization and invasion of pathogens in the intestine and an immune response that promotes the development of these diseases.
In addition, the microbiota is involved in the synthesis of essential vitamins, such as vitamins B and K, and in the production of essential amino acids, thus contributing to the overall nutrition of the host. Intestinal microorganisms are also essential in the metabolism of bile acids, a process that influences the digestion and absorption of fats, as well as the excretion of cholesterol.
Microbiota and its Role in Metabolism
The gut microbiota plays a crucial role in the host's metabolism through the fermentation process of undigested food substrates in the small intestine. These substrates, especially dietary fiber, are broken down by the gut microbiota, which has specific enzymes for them, synthesizing short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate. These metabolites not only have beneficial effects on colon health, but also influence the overall metabolism of the body.
Butyrate, for example, is a crucial energy fuel for colonic epithelial cells, helping to maintain the integrity of the intestinal barrier and prevent inflammation. Butyrate also has anti-carcinogenic properties, stimulating apoptosis of tumor cells and inhibiting their proliferation. Propionate and acetate, on the other hand, are involved in the regulation of glucose and lipid metabolism in the liver and peripheral tissues, thus playing an important role in body weight control and obesity prevention.
In addition, SCFAs modulate immune responses both locally, in the gut, and systemically. They influence epithelial barrier function, mucus production, and the secretion of antimicrobial compounds, thus contributing to protection against pathogens. SCFAs can also influence the differentiation and function of immune cells, including regulatory T cells, and modulate the production of pro- and anti-inflammatory cytokines, thus balancing the immune response and preventing excessive inflammation.
In addition to these roles, SCFAs also interact with specific receptors on epithelial and immune cells, such as G protein-coupled receptors (GPCRs), thereby influencing a variety of cell signaling pathways. This interaction may have significant implications in the regulation of appetite, intestinal motility, and insulin sensitivity.
At the intestinal lumen, bacteria produce various metabolites and contain structural elements that act as signaling molecules for certain types of cells in the intestinal mucosa. These enteroendocrine cells in the intestinal mucosa secrete a series of hormones that play a role in regulating key metabolic processes, insulin sensitivity, glucose tolerance, fat storage, appetite. Many essential features of metabolic diseases (obesity, type 2 diabetes, cardiovascular disease and hepatic steatosis) have been shown to be modulated by microbial products and metabolites and scientific evidence supports a causal role of the intestinal microbiota in the development of these diseases.
The link between the microbiota and obesity, a metabolic disease, is not yet clear. However, clinical and laboratory studies have shown a reduction in alpha diversity in obese subjects compared to an increased level of Christensenellaceae bacteria in lean individuals.
Type 2 diabetes is a metabolic disease for which studies of the composition of the microbiota have been conducted. Low numbers of butyrate-producing bacteria including Faecalibacterium , Clostridium , Pseudoflavonifractor , Roseburia , Oscillibacter and Alistipes are characteristic of both prediabetic subjects and those under treatment for type 2 diabetes. Disruption of the dynamics of interaction between bile acids and intestinal microbiota leading to altered levels of bile acids in the blood has been associated with insulin resistance and type 2 diabetes.
At the same time, the global composition of the microbiome can be predictive of a large number of cardiometabolic blood markers such as pre- and postprandial glycemic index, lipid and inflammatory. Gut microbiota metabolites such as trimethylamine N-oxide (TMAO) and more recently phenyl acetyl glutamine are correlated with the incidence and evolution of cardiovascular diseases and bacterial DNA has been identified in atherosclerotic plaques. Damage to the intestinal barrier allows lipopolysaccharides (endotoxins) originating from Gram-negative bacteria to enter the bloodstream and which are recognized by receptors on the surface of immune cells leading to the release of proinflammatory cytokines. Blood concentrations of these lipopolysaccharides are indicators of major cardiac events for many patients with atrial fibrillation suggesting that endotoxin translocation has an impact on cardiovascular disease complications.
In conclusion, the gut microbiota and its metabolites play a vital role in maintaining the health of the intestinal mucosa and the metabolic homeostasis of the whole organism. A detailed understanding of these processes offers important insights for the development of therapeutic strategies in the management of metabolic, inflammatory diseases and even some forms of cancer.
The Interaction of the Microbiota with the Immune System
The gut microbiota plays a fundamental role in the development and proper functioning of the immune system. This complex interaction between commensal microorganisms and immune cells is crucial for maintaining the balance between immunological tolerance and effective immune response.
First, the gut microbiota is essential in the development of the immune system during the neonatal period and childhood. Commensal microorganisms are involved in “educating” the immune system, helping to differentiate immune cells and develop a balanced immune response. This includes influencing the development of regulatory T cells, which are essential for preventing autoimmune reactions and excessive inflammation.
The microbiota interacts with the immune system at both the innate and adaptive levels. Within the innate immune system, commensal microorganisms can activate immune cells, such as dendritic cells and macrophages, that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). This recognition is crucial for initiating appropriate immune responses.
On the other hand, in adaptive immunity, the microbiota influences the differentiation and function of T and B lymphocytes. For example, certain bacterial species in the intestinal microbiota can induce the production of specific antibodies or stimulate the development of certain T cell subpopulations, such as T helper cells or T regulatory cells. These interactions are essential for maintaining a balanced immune response and preventing the development of autoimmune or inflammatory diseases.
The gut microbiota also contributes to the formation of immunological tolerance, a process by which the immune system learns to distinguish between beneficial commensal microorganisms and potential pathogens. This tolerance mechanism is vital for preventing exaggerated immune reactions to normal components of the microbiota and foods, thereby reducing the risk of food allergies and inflammatory bowel diseases.
Bacterial fermentation products in the gut play a key role in host immune responses that maintain the integrity of the intestinal mucosal barrier by controlling luminal microbes. For example, TLR-5 (cell receptor) recognizes flagellin, a component of the bacterial flagellum, causing it to be perceived as an antigen and triggering the differentiation of B lymphocytes into IgA (immunoglobulin A)-producing cells. IgA binds to bacterial antigens, neutralizing pathogens and preventing infection.
The Impact of Internal and External Factors on the Microbiota
The gut microbiota is a highly dynamic ecosystem that can be significantly influenced by various factors. Among these factors, diet, medication use, stress, age, and other external influences play a crucial role in maintaining or disrupting the balance of this microbial community.
Diet: has a direct impact on the composition of the gut microbiota. Extreme diets such as those based entirely on plants or proteins can significantly alter the composition of the microbiota. Foods rich in fiber, such as fruits, vegetables and whole grains, favor the growth of beneficial bacteria, while a diet high in saturated fats and sugar can lead to an increase in potentially pathogenic bacteria. Probiotics and prebiotics in food can also positively alter the composition and functions of the microbiota.
Medications: Antibiotics in particular can have a dramatic effect on the gut microbiota. Antibiotics, while essential for treating bacterial infections, can destroy beneficial bacteria and promote the growth of antibiotic-resistant strains, leading to dysbiosis. Other medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors, can also have adverse effects on the microbiota.
Stress: both physical and psychological, can also influence the gut microbiota. The mechanisms by which stress affects the microbiota include changes in gastrointestinal motility, gastric acid secretion, intestinal permeability, and even the immune response. These changes can lead to an imbalance in the microbial community, favoring the growth of pathogenic bacteria or reducing microbial diversity.
Age: is a determining factor for the composition of the microbiota. In children and the elderly, the microbiota is characterized by a low concentration of bacteria, and the Firmicutes : Bacteroidetes ratio has values of 0.4 and 0.6 respectively. In comparison in adults, this ratio has a value of 10.9. Another indicator for the compositional profile of the microbiota of elderly people is given by the increase in the concentration of E. Coli and Bacteroidetes and the decrease in the concentration of butyrate-producing bacteria ( Faecalibacterium prausnitzii ).
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