bubble_chart Overview

The gastrointestinal tract of healthy individuals harbors a diverse array of microorganisms, collectively known as the gut microbiota. These microbial communities exist in specific proportions, mutually constraining and depending on each other, forming an ecological balance in terms of both quality and quantity. However, when internal or external environmental changes occur—particularly with the prolonged use of broad-spectrum antibiotics—sensitive intestinal bacteria are suppressed, allowing unchecked bacteria to proliferate. This disruption leads to an imbalance in the microbiota, where the normal physiological composition is disturbed, giving rise to a pathological configuration. The resulting clinical symptoms are termed intestinal dysbacteriosis (alteration of intestinal flora). The incidence of this condition is approximately 2–3%.

bubble_chart Etiology

(1) Dietary Factors: Studies using bacterial enzyme assays to investigate microbial metabolic activity have shown that diet can significantly alter fecal microbiota. Fiber-deficient diets promote bacterial translocation. Spaeth G's rat experiments demonstrated that dietary fiber maintains the normal ecological balance of gut microbiota, and the end products of bacterial fiber metabolism have trophic effects on small intestine epithelium. Fiber also supports normal metabolism and cell kinetics of intestinal mucosal cells. Hosoda et al. reported that low-residue diets supplemented with fiber effectively preserve intestinal structure and function, though whether this protective effect occurs through direct mucosal stimulation or induced release of trophic gastrointestinal hormones remains unclear. Dietary fiber reduces bacterial translocation but cannot fully restore barrier function to normal levels.

(2) Microbial Population Variation Factors: While microbiota composition varies between individuals, it remains remarkably stable within a single individual over extended periods. The ecological niche of each bacterial species is determined by host physiology, interbacterial interactions, and environmental influences. Under equilibrium conditions, all ecological niches are occupied. Temporary colonization by bacteria can alter this ecological balance.

(3) Drug Metabolism Factors: Gut microbiota play crucial roles in metabolizing various drugs including lactulose, sulfasalazine, and levodopa. Any antibiotic can alter colonic microbiota, depending on its antimicrobial spectrum and intestinal concentration. Clindamycin and ampicillin can create an ecological vacuum in the large intestine, allowing Clostridium difficile overgrowth. H₂ receptor antagonists like cimetidine may cause drug-induced hypochlorhydria and gastric bacterial overgrowth.

(4) Age Factors: Intestinal microbiota balance changes with aging - bifidobacteria decrease while Clostridium perfringens increases. This bifidobacterial reduction may weaken immune stimulation, while clostridial increase elevates toxin production that suppresses immunity. Maintaining youthful gut microbiota composition in elderly individuals might enhance immune function.

(5) Gastrointestinal Immune Dysfunction Factors: Normal GI immune function derives from mucosal lamina propria plasma cells producing abundant immunoglobulins, particularly secretory IgA - the primary defense against bacterial invasion. Impaired mucosal synthesis of monomeric/dimeric IgA or secretory component leads to deficient secretory IgA in GI fluids, causing small intestinal aerobic/anaerobic bacterial overgrowth and subsequent dysbiosis with chronic diarrhea. Even asymptomatic IgA-deficient individuals may develop small intestinal bacterial overgrowth. The high incidence of neonatal dysbiosis may relate to immature immune system development.

bubble_chart Pathological Changes

(1) Bacterial Overgrowth: Anatomical and physiological abnormalities of the gastrointestinal tract can lead to the proliferation of colonic-type flora in the proximal {|###|}small intestine{|###|}, resulting in various metabolic disorders, including steatorrhea, vitamin deficiencies, and carbohydrate malabsorption. It may also occur concomitantly with {|###|}small intestine{|###|} pseudo-obstruction, scleroderma, diabetic autonomic neuropathy, chronic malnutrition, and other conditions. Bacterial overgrowth in the {|###|}small intestine{|###|} involves various anaerobic bacteria (primarily Bacteroides, Bifidobacteria, Veillonella, Enterococci, and Clostridia), which can hydrolyze conjugated bile salts, leading to impaired micelle formation, liver cirrhosis, and hypochlorhydria without significant metabolic disturbances. Changes in colonic flora can cause D-lactic acidosis due to extensive {|###|}small intestine{|###|} resection accompanied by neurological dysfunction. The use of broad-spectrum antibiotics, particularly clindamycin and ampicillin, can promote the proliferation of Clostridioides difficile, which produces a protein toxin, causing necrosis and ulceration of the colonic {|###|}membrane{|###|}, known as pseudomembranous colitis.

(2) Bacterial Production of IgA-Degrading Enzymes: Hemolytic streptococci, viridans streptococci, pneumococci, Haemophilus influenzae, Neisseria meningitidis, and Neisseria gonorrhoeae can produce proteases that degrade IgA, breaking down both serum IgA ₁ and secretory IgA in colostrum. The first two bacterial groups are major constituents of the oral flora, while the latter four are highly virulent pathogens that proliferate on mucosal surfaces. Thus, IgA protease is crucial for these bacteria to survive as commensals or act as pathogens on mucosal surfaces.

(3) Gut Flora and {|###|}Subcutaneous Node{|###|} Cancer: Colonic flora produce various metabolically active enzymes that mediate the conversion of natural products, food preservatives, dyes, additives, and pollutants into mutagenic substances. Prolonged exposure to substrates can enhance the activity of bacterial enzyme systems. If the substrate is a procarcinogen, long-term exposure may increase the production of carcinogenic substances.

bubble_chart Clinical Manifestations

Symptoms and Signs

This condition is primarily characterized by severe diarrhea or chronic diarrhea. During antibiotic treatment, if sudden onset of diarrhea occurs or existing diarrhea worsens, this condition may develop. The diarrhea is often pale yellow-green watery stools, sometimes resembling egg drop soup. Fungal infections may present as foamy loose stools with a foul odor, or bloody stools; staphylococcal infections may produce yellow-green loose stools, occurring 3 to over 20 times a day, accompanied by abdominal distension and fullness. Abdominal pain is generally mild, but severe vomiting and diarrhea may lead to dehydration, electrolyte imbalances, elevated blood urea nitrogen, and lowered blood pressure. Candida albicans infections usually start in the upper digestive tract, spreading to the small intestine or even the perianal area. Thrush is often the earliest sign of Candida enteritis. If the small intestinal mucosa becomes eroded or ulcerated, it can cause frequent, odorless mucopurulent stools, sometimes presenting as watery diarrhea, accompanied by indigestion. If treatment is inadequate, the infection may spread to the respiratory tract, urinary tract, or even brain tissue. Pseudomonas aeruginosa infections can produce blue-green fluorescent pigments, giving stools a green hue, though diarrhea is not always present. In some cases, stools may appear powdery. Abdominal pain is generally mild, with a few cases accompanied by nausea and vomiting. Most cases involve water and electrolyte imbalances, and severe cases may lead to shock. Some travelers may experience intestinal flora imbalance due to changes in climate and environment, commonly referred to as non-acclimatization. In recent years, with the widespread use of refrigerators, some households store large quantities of meat and vegetables for extended periods, leading to food spoilage. Consumption of such food can disrupt intestinal flora, causing vomiting and diarrhea, and in some cases, lack of concentration or even mental confusion.

Clinically common types of intestinal flora imbalance include:

(1) Candida albicans enteritis: The most common type of intestinal flora imbalance. It often occurs in weak infants, individuals with indigestion, malnutrition, diabetes, malignant tumors, or those on long-term antibiotic or hormone therapy.

(2) Staphylococcal enteritis: Frequently seen in elderly patients or those with chronic sexually transmitted diseases who have undergone long-term antibiotic treatment (e.g., tetracyclines, ampicillin) or adrenal corticosteroid therapy, or intestinal surgery.

(3) Clostridium perfringens acute necrotizing enteritis: The β-toxin produced by Clostridium perfringens can cause acute necrotizing tumors. Infections are most likely to occur in cases of wasting diseases or with the use of antibiotics and corticosteroids.

(4) Pseudomonas aeruginosa intestinal infection: Pseudomonas aeruginosa is an opportunistic pathogen, often causing secondary infections. It is most likely to occur in infants, the elderly, individuals with certain malignant tumors or wasting diseases, or those using antibiotics or corticosteroids.

(5) Proteus intestinal infection: Under certain conditions, Proteus can act as an opportunistic pathogen. For example, Proteus vulgaris, Proteus mirabilis, and Morganella morganii can cause food poisoning, while Proteus inconstans can lead to summer diarrhea in infants.

(6) Klebsiella pneumoniae intestinal infection: When the body's resistance is weakened or due to other factors, the normally present Klebsiella pneumoniae in the intestines can cause infections, particularly severe diarrhea in children.

bubble_chart Auxiliary Examination

(1) Microbiota Analysis: This is the primary examination method, consisting of two types: qualitative analysis and quantitative analysis.

1. Qualitative Analysis: Similar to general microbiological examinations. For example, in staphylococcal enteritis, Gram staining of fecal smears may reveal clusters of Gram-positive staphylococci and polymorphonuclear neutrophils, while fecal cultures may show abundant growth of staphylococci. For Candida albicans enteritis, pathological specimens can be directly smeared, treated with potassium hydroxide solution, and Gram-stained. Microscopic examination may reveal clusters of oval-shaped Candida albicans, which are Gram-positive with uneven intracellular staining. Bacterial cultures may form smooth, cream-colored bacterial colonies with a yeast-like odor. However, except for Grade III dysbiosis (i.e., microbial succession), other degrees of imbalance are difficult to analyze. Therefore, in addition to qualitative testing, further quantitative testing is necessary to determine whether the values are normal.

2. Quantitative Analysis: First, the fecal sample must be homogenized and diluted in a certain ratio. After culturing, colony counts of various bacterial types must be calculated to determine the total bacterial count. This process is cumbersome and rarely adopted by general laboratories. The culture media used for normal microbiota analysis require high selectivity, such as S medium for enteric pathogens, eosin methylene blue (EMB) medium for aerobic Gram-negative bacilli in the intestines, 7.5% sodium chloride agar for staphylococci, and Sabouraud agar for fungi. In addition to aerobic culture, anaerobic culture may also be necessary when required. Aerobic culture follows standard bacterial culture methods, while anaerobic culture employs biological anaerobic methods or anaerobic jar techniques.

(2) Colonoscopy: The intestinal mucosa shows diffuse congestion, edema, and indistinct or obliterated vascular branching. There are scattered erosions, ulcers, and hemorrhages, sometimes with yellow pseudomembranes attached.

bubble_chart Treatment Measures

(1) Systemic Support Therapy: For patients undergoing major surgery, attention should be paid to nutritional supplementation before the operation, and gamma globulin can also be injected intramuscularly to enhance immune function. Studies have shown that intramuscular injection of immunoglobulin in patients with ulcerative colitis can increase the number of Lactobacillus and Bifidobacterium in the colon and reduce certain opportunistic pathogens. Transfer factor, immune ribonucleic acid, thymosin, etc., can also be tried. Interleukin-2 can also be used, with 50,000 U injected intramuscularly each time for a 10-day course, which can be applied continuously.

(2) Etiological Treatment: For example, excessive proliferation of enterococci caused by megacolon or cholecystitis; reduction or disappearance of enterococci due to vitamin deficiency; or excessive yeast due to rapid small intestine motility—these underlying causes must be eliminated before normal flora can be restored to achieve efficacy.

(3) Adjustment of Flora Therapy:

1. Dietary Adjustment: For fermentative diarrhea, carbohydrate intake should be restricted; for putrefactive diarrhea, protein intake should be limited. To enhance the local defensive barrier function of the intestinal mucosa and prevent bacterial translocation, fiber-rich foods should be increased.

2. Antibacterial Drugs: The original antibiotics should be discontinued immediately. Based on flora analysis and antibacterial sensitivity tests, appropriate antibiotics should be selected to suppress overgrown bacteria, thereby indirectly supporting undergrown intestinal bacteria. Additionally, broad-spectrum antibiotics can be used to eliminate most intestinal bacteria, followed by the administration of a suspension of normal intestinal flora to restore balance.

3. Live Bacterial Preparations: Currently commonly used live bacterial preparations include Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus lactis, Lactobacillus sporogenes, Bifidobacterium bifidum, Streptococcus faecalis, large intestine bacillus, fecal bacillus, and Bacillus subtilis. Among these, Bifidobacterium bifidum preparations show the best efficacy. Bacillus subtilis preparations also perform well, possibly because this aerobic bacterium absorbs oxygen, reduces the redox potential in the intestinal lumen, and supports the growth of anaerobic bacteria (e.g., Bacteroides, Lactobacillus), thereby indirectly restoring normal flora. A compound formula of live bacterial preparations made from normal human stool suspension can also be used to treat pseudomembranous colitis caused by Staphylococcus, with good results. Lactasin, made from Streptococcus lactis, is widely used clinically with good effects. Preparations made from resistant strains of undergrown normal intestinal flora can also be used to facilitate colonization, which is an effective method for adjusting intestinal flora imbalance. The latest biological product, Lizhu Chang Le (Huichunsheng Capsule), is a live Bifidobacterium preparation (bifidobiogne). Pharmaceutical studies indicate that this preparation has barrier effects, controls endotoxemia, provides nutritional support, exhibits antitumor activity, enhances immunity, and has anti-aging effects.

4. Flora Promoters: Oral flora promoters can also achieve the goal of restoring normal flora. For example, lactose can be used to support intestinal bacilli, folic acid to support enterococci, and bifidus factors are commonly used in children to promote the growth of Bifidobacterium bifidum. The application of galactoside-fructose, which is broken down by bacteria to form lactic acid or vinegar acid, lowers pH, inhibits other bacteria, and supports Lactobacillus growth.

5. Drug-Resistant Enterococcus Preparations: Japanese researcher Meguro et al. used a thickened serial culture method to obtain a strain of enterococcus—Streptococcus BIO-4R—resistant to streptomycin, erythromycin, tetracycline, and ampicillin. Animal and human trials have shown that this strain is resistant to multiple antibiotics, thereby preventing abnormal proliferation of other flora, overcoming flora imbalance, and improving abnormal stool characteristics. It is more effective and faster than traditional antibiotic therapy alone and can prevent the transfer of resistance factors from Streptococcus faecalis BIO-4R to large intestine bacillus K-12. {|107|}

6.Chinese medicine Chinese medicinals：Chinese medicine believes: "The root of diarrhea lies invariably in the spleen and stomach." Acute diarrhea diseases are mostly excess syndromes, attributable to the spleen and stomach; chronic diarrhea diseases are often deficiency syndromes, frequently involving the spleen and kidneys. The former should be treated by clearing heat and resolving dampness, while the latter requires strengthening the spleen and kidneys. Heat-clearing and detoxicating medicinals in Chinese medicine affect humoral immunity. For example, Dandelion and Hedyotis can promote antibody production, and Heartleaf Houttuynia Herb can increase the concentration of properdin. The properdin system, composed of properdin, ₃, and Mg⁺⁺, has a certain bactericidal effect on gram-negative bacilli such as dysentery bacillus, Salmonella, and Pseudomonas aeruginosa. This system represents an important non-specific immune defense function before the body produces antibodies. When using Chinese medicine's pattern identification and treatment for intestinal flora imbalance, the effects of the aforementioned medicinals should be considered. Combining them appropriately in methods such as clearing heat and resolving dampness, tonifying qi and invigorating the spleen, harmonizing the stomach and eliminating dampness, or warming the kidneys and strengthening the spleen can yield relatively ideal results.

bubble_chart Prognosis

Intestinal flora imbalance symptoms generally have a good prognosis, except in cases of severe vomiting, diarrhea, dehydration, blood loss, toxemia, or even shock, where the prognosis is poorer.

bubble_chart Prevention

Use antibiotics appropriately. For the elderly, physically weak individuals, and those with chronic debilitating diseases, strictly adhere to indications when using antibiotics or hormones. It is best to conduct drug sensitivity tests to select the most effective antibiotics. For the elderly, infants, and those weakened by illness, consider combining antibiotics with probiotics like lactobacillus or live bifidobacterium preparations, along with B vitamins or vitamin C, to prevent intestinal flora imbalance. Before major surgeries, ensure comprehensive supportive therapy, such as improving nutrition, blood transfusions, intramuscular gamma globulin injections, and vitamin supplementation.