ECOLOGICAL BIOCHEMISTRY - Tutorial - V. M. Isaenko 2005

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

2.8. Human gastrointestinal diseases associated with imbalances in the normal microflora

Inflammatory processes and ulcers. The Role of Helicobacter pylori infection in The Development of inflammatory processes, erosions, and ulcers of the digestive tract is beyond doubt. Numerous studies have demonstrated a high degree of colonization by these microbes in patients with PEPTIC ULCER DISEASE, as well as Chronic gastritis, non-ulcer dyspepsia, and Gastric Cancer.

The effectiveness of anti-Helicobacter therapy in preventing disease relapses further Supports the role of Helicobacter in the Etiology of gastric and duodenal diseases.

Numerous studies have investigated the mechanisms underlying inflammatory and ulcerative processes induced by Helicobacter infection. It has been found that certain strains of Helicobacter produce cytokines and mucinase, which cause the proteolysis of mucin in the gastric mucosa and deplete the mucous layer, thereby amplifying the destructive action of gastric juice. The accumulation of ammonia resulting from bacterial urease activity is also significant.

Helicobacter species disrupt The regulation of prostaglandin and gastrin production, as well as other substances, and promote the release of cytokines, notably interleukin IL-8, which triggers epithelial Cell destruction. Their action leads to a localized accumulation of histamine in the gastric mucosa, which is known to stimulate gastric secretion.

Clinical manifestations of Small Intestine damage in chronic enteritis are primarily caused by The impact of toxic bacterial metabolites on the intestinal mucosa, as well as their absorption from the intestinal lumen into the bloodstream. Bloating, flatulence, and abdominal pain arise from intensified Fermentation and putrefactive processes in the small intestine.

Bacterial carbohydrate fermentation in the small intestine is accompanied by The production of large amounts of hydrogen, methane, carbon dioxide, volatile Fatty acids, and Other Compounds, leading to abnormal carbohydrate fermentation, incomplete Digestion, and malabsorption in the small intestine.

Anaerobic Bacteria metabolize dietary Proteins to produce ammonia and compete with the host Organism for incoming protein substrates. All of this leads to protein malabsorption syndrome, disruption of plastic processes in the body—including the regeneration of the intestinal epithelium—as well as weight loss and diminished pancreatic function. A deficiency of numerous Vitamins develops, particularly Vitamin B12, which is utilized by various anaerobic intestinal bacteria. Mineral absorption is also impaired, with some minerals, such as iron, becoming sorbed onto The surface of bacterial Cells.

It has been established that intestinal microorganisms can stimulate or inhibit intestinal peristalsis by producing bradykinin, morphine-like substances, and Prostaglandins, as well as by altering Bile acid METABOLISM and synthesizing serotonin, which regulates motility and smooth Muscle tone.

Despite the lack of direct data indicating a role for dysbiosis in the development of chronic constipation, alterations in the microbial flora of constipated patients are frequently observed. Experimental data have proven that germ-free mice exhibit slowed intestinal peristalsis, which increases following the administration of microorganisms.

Carcinogenesis. The most frequent sites for tumors of the Digestive System are The Stomach—in cases of reduced gastric secretion—and the Large Intestine, particularly the rectum, which are the Regions of the digestive tract most densely colonized by microorganisms.

Analysis of the microflora in patients with Various Forms of gastric cancer reveals significant qualitative and diverse quantitative differences in microorganisms—such as various associations of Escherichia, staphylococci, enterococci, pseudomonads, Candida, and other aerobic bacteria—compared to healthy individuals. A characteristic feature of the microflora in tumor patients is the presence of A large number of spore-forming aerobic bacteria in the gastric contents.

Aerobic and anaerobic microorganisms, permanently or transiently present in the host's digestive tract, are capable of metabolizing various exogenous and endogenous substrates not only to degrade and eliminate them from the body, but also to generate intermediate or final products that can stimulate tumor growth.

Experimental studies using various animal models (germ-free and with defined microflora) indicate a significant role of the microflora in the development of Liver and intestinal tumors. For example, nitrates are converted into nitrosamines—potent carcinogens—through the action of Enzymes produced by hemophilic bacteria, clostridia, peptococci, eubacteria, actinomycetes, propionibacteria, and bacteroides.

At the same time, microorganisms such as lactobacilli, bifidobacteria, and streptococci are weak producers of nitroreductases. The reduction of nitrates to nitrites begins already in the Oral Cavity under the Influence of the microflora. Similar processes can occur with Glycosides found in many plant-derived foods, which are not inherently carcinogenic. Under the action of bacterial glycosidases, certain plant glycosides are converted into derivatives with carcinogenic properties.

Furthermore, secondary bile acids have been found to exhibit strong toxicity toward the gastric mucosa. High mutagenic activity has been established for lithocholic and deoxycholic bile acids, and the higher their ratio, the greater the risk of developing colorectal and breast cancer.

There is evidence that the consumption of certain fats, as well as Cholesterol, correlates with the risk of breast and digestive system cancers. Normally, cholesterol entering the large intestine is metabolized by bacteria into coprostanol and coprostanone. However, the intake of a high-cholesterol diet leads to elevated levels of coprostanol and coprostanone, which may be one of the factors accelerating tumor growth.

The leading role of the intestinal microflora in the Circulation and metabolism of Sex Hormones has also been proven. Microbial enzymes deconjugate bound estrogens, As a result of which the hormones are easily reabsorbed from the intestinal lumen.

Pathogenic bacteria are likewise capable of converting hormone molecules into compounds with carcinogenic properties.

The intestinal microflora participates in The formation of carcinogens from Amino Acids, primarily Methionine, Tyrosine, and Tryptophan. While these Amino acids are not carcinogens themselves, they are converted by certain bacterial strains into metabolites exhibiting carcinogenic activity.

The human intestinal microflora can act as a factor that accumulates large amounts of various environmental toxic agents, functioning as natural sorbents, while on the other hand, it is capable of acting as a producer of carcinogens. In this context, the interaction between MICROORGANISMS AND THE epithelial Cells of the digestive tract mucosa is of critical importance.

The anticarcinogenic role of lactic acid bacteria has been well established. The anticarcinogenic action of lactobacilli is based on mechanisms such as the inactivation of procarcinogens present in food, the inhibition of mutagen-producing enzymes, The stimulation of immune mechanisms for antitumor defense, and the production of compounds (such as butyric acid) capable of inhibiting tumor cell proliferation. Lactobacilli reduce the fecal levels of tumor growth promoters, such as free amines, azoreductases, and nitroreductases. Lowering the pH of the intestinal contents reduces the Formation of secondary bile acids and decreases the incidence of cancer.

Bifidobacteria also exhibit antitumor activity. They are capable of binding heterocyclic carcinogenic amines formed in foods as a result of thermal Processing.

Allergy. Allergy-related disorders are extremely widespread. A wealth of research highlights the role of the microbial flora in the development of allergic processes. It has now been proven that many Representatives of the microbial world—such as streptococci, clostridia, and enterobacteria—have The ability to synthesize histamine and other amines, which affects the levels of these substances in the body's biological fluids and Tissues.

The role of Microorganisms in the development of allergic processes is supported by evidence that Probiotics have a positive therapeutic effect on allergic diseases, particularly those based on live microorganisms representing the normal intestinal microflora. The Treatment efficacy is driven by the ability of the normal microflora to stabilize the intestinal mucosal barrier, reduce inflammatory processes in the mucosa, normalize immunological imbalances, prevent the adsorption of food Antigens, and eliminate increased intestinal permeability. Furthermore, the antiallergic activity of lactobacilli, bifidobacteria, and certain Yeast strains has been proven.