Low Stomach Acid [ Hypochlorydria ] 

 

When gastric acid secretion is reduced, a condition known as hypochlorhydria, the stomach and upper small intestine become less acidic. This loss of acidity weakens a critical antimicrobial barrier, allowing ingested bacteria and oral flora to survive transit through the stomach. As a result, a greater number of bacteria can enter and colonize the small intestine, contributing to the development of SIBO.

 

Gastric acid is also essential for converting pepsinogen into pepsin, the enzyme that initiates protein digestion. Pepsin breaks dietary proteins into smaller fragments called peptides, which are then further digested into amino acids for absorption in the small intestine. When this process is impaired, larger protein molecules remain undigested, providing a nutrient source for bacteria in the small bowel.

 

Bacterial metabolism of these undigested proteins produces fermentation byproducts such as ammonia, hydrogen sulfide, and other metabolites. These substances can disrupt the local environment and create conditions that favor further bacterial proliferation. Over time, this cycle can sustain or worsen bacterial overgrowth in the small intestine. [4][5][25]

 

Poor Enzyme Output [ Enzymatic Maldigestion ]

 

The pancreas plays a central role in digestion by producing and secreting key digestive enzymes into the small intestine. These include:

 

• Amylase: which breaks down complex carbohydrates (starches) into smaller sugar units, such as glucose, for absorption.

• Lipase: which hydrolyzes dietary fats into free fatty acids and glycerol, enabling their absorption across the intestinal lining.

• Proteases: which cleave dietary proteins into smaller peptides and ultimately into amino acids.
   

When pancreatic enzyme output is reduced, a condition known as pancreatic insufficiency, the digestion of proteins, fats, and carbohydrates becomes incomplete. This leaves larger, undigested food particles in the small intestine.

 

These undigested substrates act as an abundant nutrient supply for bacteria, supporting their survival and growth in a region of the gut that normally contains relatively few microbes. Over time, this can facilitate bacterial overgrowth in the small intestine, perpetuating the cycle of maldigestion and SIBO. [2][6][19]

 

Impaired Bile synthesis [ Hepatic Insufficiency ] 

 

Liver insufficiency can contribute to SIBO development through its impact on lowering bile production and secretion. Bile contains bile acids that are essential for the emulsification / breakdown and absorption of dietary fats.

 

When liver detoxification or bile synthesis is impaired, there is a reduction in both bile acid concentration and bile flow into the small intestine. Inadequate bile relative to fat intake results in unabsorbed dietary fats remaining within the intestinal lumen.

 

These unabsorbed fat globules can:

 

• Alter intestinal pH, creating an environment less favorable for normal digestive processes.

• Slow intestinal transit, reducing the clearance of bacteria from the small bowel.

• Trigger mucosal inflammation, which can impair local immunity.
   

Collectively, these changes support the establishment and persistence of bacterial overgrowth. Additionally, some bacterial species possess enzymatic systems enabling them to utilize fats and fat-derived metabolites as an energy source. The presence of undigested fats therefore provides both a favorable environment and a direct nutrient supply for such bacteria, promoting their replication and contributing to the progression of SIBO. [4][19]

 

Parasitic or Worm Infection [ Helminth or Protozoa Infection ] 

 

​​Parasitic or Worm Infections, including helminths worms such as roundworms, hookworms, and tapeworms, or protozoa such as Giardia lamblia or Entamoeba histolytica, can be a significant contributing factor in SIBO pathophysiology.

 

When these organisms infiltrate the gastrointestinal  tract, they can trigger chronic enteric immune activation, meaning persistent stimulation of the gut’s immune defences. This ongoing immune engagement can divert immune resources away from other important functions, such as controlling bacterial populations in the small intestine. As a result, the ability to suppress or eliminate bacterial overgrowth is reduced.

 

In addition, the inflammation and mucosal irritation caused by these infections can impair the coordinated muscular contractions that move food through the digestive tract. This reduced motility slows the clearance of contents from the small bowel, giving dietary substrates, particularly sugars, more time to be metabolised by bacteria. This prolonged exposure supports bacterial proliferation and fermentation, producing gas and other metabolic byproducts that contribute to the symptom profile of SIBO. [4][7]

 

Sluggish Movements [ Hypomotility ] 

 

Motility refers to the coordinated contractions of the small intestine that propel contents forward. It is a cyclic, recurring pattern of electrical and muscular activity, which functions as the gut’s cleaning wave, sweeping residual food particles and bacteria from the small intestine toward the colon. This process helps maintain the small bowel’s normally low bacterial population by physically clearing organisms before they can establish colonies. If motility is impaired bacteria have more time to remain in place and replicate greatly increasing the risk of SIBO. [4][8][25]

 

Hypothyroidism 

 

Hypothyroidism slows down overall metabolic processes, including the neuromuscular activity of the gastrointestinal tract. Reduced thyroid hormone levels decrease muscle contractility, which in turn impairs the rhythmic contractions that move food and waste along the digestive tract. When bowel motility slows, digestive residues and bacteria remain in the small intestine for longer periods. This extended transit time gives bacteria more opportunity to replicate. Over time, this can facilitate bacterial overgrowth in the small intestine, increasing the risk of SIBO. [11]

 

Dysbiosis 

 

Dysbiosis refers to a disruption in the normal microbial balance of the gastrointestinal tract, characterised by an overgrowth of pathogenic or opportunistic bacteria alongside a reduction in beneficial commensal species. Within the small intestine, this imbalance undermines several protective mechanisms that normally inhibit bacterial overgrowth.

 

An example of this is beneficial microbes, such as Lactobacillus and Bifidobacterium, produce bacteriocins, which are antimicrobial peptides that suppress competing bacterial populations by disrupting their cell membranes or interfering with metabolic processes. Other beneficial species secrete compounds that modify the mucosal surface or compete for epithelial binding sites, thereby preventing pathogenic bacteria from attaching to and colonising the intestinal lining. In the absence of firm adhesion, pathogens are more easily cleared through coordinated intestinal motility.

 

Therefore, when dysbiosis develops, these protective mechanisms are diminished, enabling pathogenic bacteria to adhere, proliferate, and persist in the small intestine. Re-establishing a balanced microbiota can help reverse established SIBO and significantly reduce the risk of recurrence. [4][9][19]

 

Impaired GALT 

 

The gut-associated lymphoid tissue (GALT) is a specialised component of the intestinal immune system embedded within the lining. It plays a central role in maintaining microbial balance by orchestrating immune responses and activating protective mechanisms including:

 

• Secretory immunoglobulin A (sIgA) production, which binds to pathogens, blocking their adherence to epithelial surfaces.

• Macrophage activation, enabling rapid recognition and elimination of microbial threats.

• Regulatory T cell modulation, maintaining immune tolerance while suppressing excessive inflammation.
   

In the context of SIBO, impaired GALT function means that immune regulation of the small intestinal microbiota is weakened, reducing the ability to control opportunistic bacterial populations. This loss of immune-mediated microbial control promotes bacterial colonisation, persistence, and symptom development. [4][10]

 

High Stress [ SNS Hyperactivation ] 

 

Stress can contribute to the development of SIBO through multiple gut-brain axis mechanisms. Chronic psychological stress activates the HPA axis, leading to sustained release of stress hormones and neurotransmitters that impair mucosal immunity. This change reduces the host’s ability to control bacterial populations, thereby creating an environment conducive to small intestinal bacterial overgrowth. Experimental evidence suggests that stress can also directly affect the balance and diversity of the gut microbiota, promoting dysbiosis and inflammatory responses that further compromise gut function and encourage SIBO. [17]

 

Fermentable Carbohydrate Intake

 

Fermentable carbohydrates contribute to the development and persistence of SIBO because they serve as readily available substrates for bacterial fermentation in the small intestine, promoting excessive bacterial growth and metabolic activity. Their fermentation produces gases, which can cause bloating, pain, and altered motility, further impairing clearance of bacteria. This creates a self-perpetuating cycle where excess substrate availability sustains overgrowth and symptoms.

 

Such Fermentable Carbohydrates Include:

 

• Fructose 

• Galactooligosaccharides 

• Resistant Starches

 

Medications: 

 

Proton Pump Inhibitors (PPIs)

 

PPIs are commonly prescribed for the treatment of gastroesophageal reflux disease (GERD) and peptic ulcers. Long-term use of PPIs has been associated with changes in gut microbiota and alterations in gastric acid production, which may increase the risk of SIBO.[14]

 

Opioid Pain Medications

 

Opioids, such as morphine, oxycodone, and hydrocodone slow peristalsis and prolong small intestinal transit, increasing luminal stasis and allowing bacteria more time to proliferate. They also alter microbiota composition toward dysbiosis. These combined effects create an environment conducive to bacterial overgrowth in the small intestine. [15]

 

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

 

NSAIDs, including aspirin and ibuprofen, are commonly used to relieve pain and inflammation. NSAIDs have demonstrated to cause mucosal injury impairing barrier integrity. They also shift gut microbiota toward less protective species. This combination of barrier disruption and dysbiosis may facilitate bacterial overgrowth in the small intestine, particularly if motility or immune defenses are compromised.[16]