ECOLOGICAL BIOCHEMISTRY - Textbook - V. M. Isaenko 2005

Chapter 2. ECOLOGICAL AND BIOCHEMICAL INTERACTIONS OF PROKARYOTES, MICROSCOPIC FUNGI, AND ALGAE WITH HIGHER PLANTS AND ANIMALS

2.7. Human digestive tract microflora and its Functions

The normal microflora of an animal Organism is a complex of numerous microbiocenoses characterized by a specific composition and occupying a particular biotope within the host organism. The total number of bacterial Cells across all microbiocenoses exceeds the total number of cells in all Tissues and Organs of the macroorganism by hundreds of times (reaching a total of 10¹⁴). This enormous quantity and diversity of microbial cells (over 400 strains) enable the normal microflora to participate in various physiological Functions of the host organism. It has been established that the normal microflora is involved in: 1) regulating the gas COMPOSITION OF THE host's intestinal lumen; 2) producing Enzymes for the METABOLISM of Proteins, CARBOHYDRATES, Lipids, Nucleic Acids, and biologically active compounds (Vitamins, Antibiotics, toxins); 3) Water-Salt Metabolism; 4) maintaining the colonization resistance of the organism; 5) the recirculation of Bile acids, Cholesterol, Hormones, and other macromolecules; 6) the absorption of iron, calcium, and vitamin D; 7) performing immunogenic and mutagenic (or antimutagenic) functions; 8) the detoxification of exogenous and endogenous substrates; 9) providing energy for the host cells.

The digestive tract of animals is an open biological system colonized by microorganisms. The composition and density of the microbial flora depend on the specific section of the digestive canal and The Nature of the diet. The resident microflora of the digestive tract mainly comprises bifidobacteria, lactobacilli, bacteroides, enterococci, escherichia, and Yeast-like Fungi. In healthy monogastric animals, the vast majority of this flora (up to 80 — 90%) consists of bifidobacteria. The second largest and most physiologically significant group of eubiotic gastrointestinal flora is lactic acid Bacteria of the genus Lactobacterium. The transient microflora of the digestive tract may be represented by bacilli (primarily clostridia), staphylococci, Yeasts, and yeast-like fungi. Under certain conditions, transient microflora can cause a range of diseases.

The human Digestive System is characterized by a specific microflora content. The Esophagus generally lacks a permanent microflora, and any microorganisms present there represent the microflora of the Oral Cavity. The microbial spectrum of The Stomach is sparse, consisting of lactobacilli, streptococci, helicobacters, and acid-resistant yeast-like fungi, the normal content of which does not exceed 10² — 10³ CFU/ml.

The microflora of the Small Intestine is sparse; in the duodenum, it is represented by streptococci, lactobacilli, and veillonellae, while other sections contain higher numbers of microbes, peaking in the jejunum, which, alongside the aforementioned microorganisms, harbors Escherichia coli and anaerobes. The concentration of Microorganisms in the Large Intestine is high, reaching 10¹² CFU/g of feces.

The microbial biomass inhabiting the human intestine constitutes 5% of body weight. Normal microflora consists of 99% anaerobic bacteria, alongside a small proportion of aerobic and facultative bacteria. The foundation of the digestive tract microflora in animals and humans comprises bifidobacteria, lactobacilli, propionibacteria, peptostreptococci, enterococci, pentococci, and bacteroides.

Bifidobacteria are the most prominent bacterial representatives in the intestines of humans and animals. The majority of these bacteria reside in the large intestine, forming its primary mucosal and luminal microflora. They persist in the intestine throughout an individual's entire life, accounting for 90 — 98% of all microorganisms, and are found in the highest quantities in infants, particularly during breastfeeding.

Lactobacilli colonize various sections of the digestive tract, notably the Oral Cavity and rectum. Through their metabolic activity, they interact with other microorganisms, thereby suppressing putrefactive and pyogenic opportunistic microbes, primarily Proteus species, as well as pathogens of acute intestinal infections.

During metabolism, lactobacilli produce lactic acid, hydrogen peroxide, Lysozyme, lactocidin, plantaricin, reuterin, and lactolin, which exhibit antibiotic activity. They also play an immunomodulatory role, encompassing The stimulation of phagocytosis, the synthesis of IMMUNOGLOBULINS, and The production of interferon and interleukin-1. In the stomach and small intestine, they serve as a primary link in establishing colonization resistance.

In cases of reduced immunological resistance and disrupted microecological balance, lactobacilli can accumulate in high concentrations and trigger the onset and development of pathological processes, predominantly in the oral cavity (thrush in infants).

Propionibacteria are anaerobic bacteria that form a group of normal acid-producing microorganisms. They produce organic acids and lower the environmental pH, which imparts antagonistic properties against pathogenic and opportunistic bacteria.

Escherichia (coliforms) appear in the human intestine within the first days after birth and persist throughout life. Their main functions include lactose Hydrolysis, participation in vitamin synthesis, and the production of colicins—antibiotic-like substances that inhibit the growth of enteropathogenic strains of E. coli. These bacteria exhibit high immunomodulatory activity, helping to activate systemic humoral and local Immunity. Normally, Escherichia inhabit the large intestine and the distal small intestine. The detection of Escherichia or other enterobacteria in the oral cavity, stomach, duodenum, or bile indicates a disruption of the eubiotic state.

Enteropathogenic strains of E. coli may be detected in the intestinal contents of healthy animals and humans; when their population increases, they can cause escherichioses manifesting as cholera-like diarrhea or dysentery-like enterocolitis.

Peptostreptococci are non-fermenting anaerobic streptococci that produce hydrogen during their metabolic activity; in the intestinal lumen, this hydrogen is converted into hydrogen peroxide, which helps maintain the pH at 5.5 or lower. They participate in the proteolysis of milk proteins and the carbohydrate Fermentation. They inhabit the large intestine.

Enterococci are intestinal streptococci whose population should normally not exceed the total number of coliforms. In the event of decreased immunoreactivity of the organism, they become causative agents of infections in the large intestine and other organs.

Bacteroides are anaerobic, non-spore-forming microorganisms inhabiting the large intestine of animals; they participate in digestive processes, deconjugate bile acids, and take part in Lipid Metabolism.

Peptococci are anaerobic cocci of the intestinal contents that metabolize peptones and Amino Acids to produce Fatty acids. When translocated to uncharacteristic niches, they can cause purulent infections.

A decrease in the number of anaerobic Representatives of the indigenous microflora, which possess high antagonistic activity against pathogenic flora, creates favorable conditions for the proliferation of opportunistic microorganisms: enterobacteria, staphylococci, and fungi (Candida).

According to the theory of adequate Nutrition, the comprehensive provision of all vital functions of the organism is achieved not only through the intake of dietary nutrients, but also via regulatory substances that act as mediators in signaling and adaptive interactions between the organism and its environment. In accordance with this theory, There are two types of nutrients. Some of these (primary nutrients) enter from the environment as components of food, whereas others (secondary nutrients) are formed within the body from precursors under the action of digestive enzymes and Other forms of biotransformation and Biosynthesis (e.g., mediated by the gastrointestinal microflora). Nutrition based on secondary nutrients predominates in animals with symbiotic feeding, such as ruminants. However, even in humans, the production and utilization of secondary nutrients play a significant role. In particular, human gastrointestinal normoflora produces vitamins and amino acids, including essential ones.

Numerous studies and publications demonstrate that the symbiotic gastrointestinal microflora under normal conditions (absence of dysbiosis, adequate nutrition) is capable of significantly meeting the macroorganism's requirements for most known vitamins—B₁, B₂, B₃, B₄, B₅, B₆, B₉, B₁₂, H, K, etc. (acting as Cofactors for enzyme systems)—as well as influencing the assimilation of these and other vitamins and Vitamin-like substances, such as vitamins A, C, E, P, D, and F (which participate in antioxidant and hormonal systems).

During gastrointestinal dysbiosis, dietary polyunsaturated fatty acids (linoleic, linolenic acids, etc.) can be transformed into saturated fatty acids (stearic acid). In this case, it can be assumed that similar processes may cause or serve as a contributing factor to the imbalance of lipid Metabolism in the Organism as a whole and in the Skin in particular. It has been established that patients with Chronic gastritis and enterocolitis harbor bacterial strains in their intestine that destroy Vitamin C. It should be borne in mind that under certain forms of dysbiosis, many vitamins and other dietary micronutrients may primarily satisfy the nutritional demands of the extraneous (including pathogenic) microflora of the digestive tract. Under such conditions, vitamins may not only fail to be absorbed but may even promote The Development of dysbiosis. For instance, clinical studies have established that under massive loads of vitamin B, toxopyrimidine appears in human urine, formed from thiamine under the Introduction/43.html">Action of Certain intestinal bacteria. This substance acts as an antagonist of vitamin B₆, inducing a deficiency state accompanied by a decrease in The activity of pyridoxal enzymes and a reduced amount of Pyridoxal phosphate in tissues.

The restoration of the vitamin-producing activity of the normoflora does not occur immediately, but over the course of 1 to 3 weeks under The Influence of dietary factors favorable to the normoflora that correct the diet—such as reducing elevated levels of animal proteins, increasing oligosaccharide content, eliminating monotonous thermally processed foods, antibiotics, and products with high concentrations of preservatives, etc. The reverse process (the decline of the vitamin-producing activity of the microflora) upon transitioning to a diet unfavorable to the

normoflora also occurs gradually over a similar period.

Main Functions of the microflora:

1. Influence on the Development of the intestine and certain other organs (differentiation of epithelial cells, crypts, and villi of the small intestine, MOTOR FUNCTION OF the digestive tract, size of the cecum, size and functions of the Pancreas, Thyroid Gland, Adrenal Glands, Liver, etc.).

2. Synthesis and regulation of vitamin absorption.

3. Absorption of salts, sorption, and excretion of metals.

4. Regulation of the metabolism of Certain amino acids (particularly Tryptophan).

5. Enzymatic Digestion of food masses.

6. Formation of immunity and nonspecific defense reactions in Postnatal development.

7. Ensuring the Stability of the normal microflora and creating a barrier against the invasion of pathogenic and opportunistic microorganisms.

Microflora also plays an active role in the activation and inactivation of various classes of drugs and Mechanisms of action (antibiotics, cardiovascular drugs, peptide and Steroid Hormones, laxatives and contraceptives, vitamins, etc.) as they pass through the digestive tract or undergo enterohepatic recirculation.

There is a close link between the intestinal microflora and liver function. This is primarily due to the liver's role in detoxifying numerous substances entering from the intestine via the PORTAL VEIN SYSTEM. However, the microflora of the mucous membranes and skin is the first to come into contact with all substances entering the body via water, food, or air.

Microbially mediated detoxification occurs through the microbial biotransformation of chemical compounds into non-toxic final products or less toxic compounds, with a portion of the incoming substances being excreted in the feces. Intestinal microorganisms are also involved in the sorption of compounds, notably heavy metal salts, phenols, and other xenobiotics.

Currently, there is sufficient convincing evidence that potentially hepatotoxic chemical compounds partially or completely lose their toxicity under the Influence of the enzyme systems of intestinal microorganisms.

It has been established that the synthesis, enterohepatic Circulation, and METABOLISM OF BILE acids, cholesterol, and steroid hormones occur with the participation of the intestinal microflora.

Intestinal bacteria are also involved in the metabolism of bile pigments. Under the influence of microbial β-glucuronidase in the digestive

tract—most actively in the distal small intestine and the cecum—conjugated bilirubin undergoes deconjugation.

Microflora is of paramount importance for the normal functioning of the animal organism. For instance, germ-free animals exhibit a decline in hematopoietic function, manifested by a reduced count of leukocytes and lymphocytes in the Blood. Such animals show alterations in the size and function of the adrenal glands and pancreas, as well as the weight of The Thyroid Gland and Ovaries. Gut microflora plays a crucial role in the functional development of pituitary FS-cells. In germ-free rats, plasma and tissue concentrations of Insulin and gastrin are significantly lower than in animals with a normal gut microflora.

Studies on germ-free (conventional) animals and gnotobiotics with a defined microbial composition have demonstrated a correlation between microbial status, food intake, and lifespan.

It has been found that germ-free animals have underdeveloped Lymphoid organs, with a markedly lower number of lymphocytes (especially epithelial ones) and plasma cells compared to conventional animals. Germ-free animals are characterized by attenuated exudative and proliferative processes during inflammation due to an insufficient amount and activity of cytokines and inflammatory mediators produced by leukocytes.

Studies on the phagocytic capacity of granulocytes in germ-free and conventional animals indicate that the uptake of Salmonella and Escherichia coli by granulocytes in vitro and in vivo occurs only when the leukocytes are harvested from conventional rats. Granulocytes from germ-free animals are incapable of capturing and digesting microorganisms.

A substantial body of data indicates that the gastrointestinal microflora plays a vital role in regulating the sorption and excretion of ions such as sodium, potassium, calcium, magnesium, zinc, iron, copper, manganese, phosphorus, and chlorine.

Observations of elderly individuals consuming milk fermented with L. acidophilus also point to the ability of certain gut microflora members to regulate Mineral Metabolism in the host organism. It was revealed that long-term consumption of live acidophilus lactobacilli leads to a significant increase in serum total calcium, its ionized form, and total phosphorus, without affecting magnesium levels. It is believed that in adult humans, gut microorganisms process up to 50 kg of endogenous material annually.

Bacteria are capable of interacting with and binding significant amounts of Metal Ions from aqueous solutions. Feces serve as the primary route for The excretion of copper, thallium, lead, zinc, cadmium, iron, and mercury, and to a lesser extent, bismuth, tin, and silver.

It has been established that lactic acid bacteria stimulate the production of interferon and interleukins in vitro and in vivo. Lactobacilli also nonspecifically activate macrophages, resulting in enhanced phagocytic activity, increased phosphatase activity, oxidative capacity, and cytostatic activity against leukemic cells. Macrophage activation by the host microflora explains the increased resistance of conventional and gnotobiotic animals to Salmonella infection compared to germ-free ones. This is also linked to the higher antitumor resistance of such organisms following oral administration of lactobacilli.

Certain strains of bifidobacteria, specific strains of lactobacilli, and yeasts sharply enhance Cell proliferation in Lymph Nodes.