Helicobacter pylori Infection 

 

Helicobacter pylori is a gram-negative bacterium that colonizes the gastric mucosa and contributes to low-grade chronic inflammation through activation of the NF-κB signaling pathway and disruption of vagal neural signaling. These mechanisms are implicated in the development of dyspeptic symptoms. H. pylori is strongly associated with 70 - 90% of peptic ulcers and has also been detected in up to 50% of patients with functional dyspepsia (FD), suggesting a pathogenic role in many FD cases." [3][7][9]

 

Helicobacter pylori is the first point of investigation. Testing can be authorised by your doctor.

 

Low Stomach Acid [ Hypochlorydria ] 

 

Low stomach acid, also known as  hypochlorhydria, has been increasingly recognized as a contributing factor in functional dyspepsia. In studies using the endoscopic gastrin test, hypochlorhydria was defined as gastric acid secretion of less than 2.1 mEq over 10 minutes. 

 

Individuals with this condition were found to have significantly higher dyspeptic symptom scores, highlighting that insufficient acid production impairs normal digestion, potentially leading to symptoms such as bloating, fullness, and discomfort. Contrary to the common belief that excess acid causes dyspepsia.[18]

 

It is important to note that Helicobacter pylori infection significantly alters gastric acid secretion. In the acute phase, H. pylori induces a temporary suppression of stomach acid, which facilitates the bacterium’s survival and establishment within the gastric mucosa. Over time, as infection becomes chronic, acid secretion may still remain low, depending on its placement in the stomach. [19]

 

Hypothyroidism

 

Hypothyroidism can contribute to symptoms of FD by impairing gastrointestinal motility, particularly through delayed gastric emptying, which affects 25% of FD patients [4]. Thyroid hormone T3 plays a vital role in maintaining normal gut motility by stimulating smooth muscle contractions and supporting the function of the autonomic nervous system. 

 

In hypothyroid states, reduced hormone levels lead to a generalized slowing of GI transit, including the stomach’s ability to empty its contents efficiently. This delay can result in the buildup of gastric contents, causing early satiety, postprandial fullness, bloating, nausea, and epigastric discomfort. 

 

Additionally, hypothyroidism may impair gastric accommodation due to diminished vagal activity, physically affecting muscle and nerve function. Clinical studies have demonstrated that many patients with untreated hypothyroidism exhibit delayed gastric emptying on scintigraphic testing, and that these symptoms often improve with appropriate thyroid support. [4][12]
 

Chronic Stress [ Sympathetic Dominance ]

 

Stress and anxiety play a major role in FD, especially by affecting how the stomach relaxes and holds food after eating. In people with FD, both short-term stress and long-term stress can make this stomach reflex work poorly. This means the stomach doesn't expand properly after meals, which can lead to feelings of fullness, bloating, and discomfort.[15]

 

Furthermore, vagal nerve activation (induced on relaxation) is associated with enhanced GI function including digestive secretions and motility. Conversely, poor vagal tone caused by persistent stress and subsequent sympathetic nervous system (SNS) activity, is linked to disturbed motility, altered gut signalling (visceral hypersensitivity) and chronic low-grade gut-derived inflammation each of which is associated with FD.[4]

 

To further this, a study of over 250 FD patients found that those with anxiety had weaker and slower stomach relaxation after eating. Their stomachs also took longer to return to normal. Even healthy people, when made anxious in the test showed similar stomach changes, supporting the idea that anxiety can immediately impair digestion.[15]

 

High Blood Sugar [ Impaired Glucose Tolerance ]

 

Elevated blood glucose levels can independently slow gastric emptying, even in individuals who do not have diabetes. The underlying mechanisms are multifactorial. Hyperglycemia disrupts vagal nerve signaling, which is essential for coordinating stomach contractions and gastric accommodation. It also alters the release of gastrointestinal hormones such as GLP-1 and motilin, both of which regulate the pace of gastric emptying. Additionally, high glucose levels can impair the function of interstitial cells of Cajal, the gastric pacemaker cells responsible for generating peristaltic waves. The net results are reduced contractions and delayed gastric emptying, creating symptoms of dyspepsia. 

 

Clinical studies using glucose infusions in healthy volunteers have shown that short-term blood sugar elevations can delay gastric emptying within hours, confirming its direct, independent effect.

This delay is also dose-dependent, the higher the blood glucose, the slower the gastric emptying. [13]

 

Epstein Barr Virus Latency

 

Epstein-Barr virus, best known for causing glandular fever, is a latent (life-long) infection that is implicated in gastrointestinal motility disorders, including delayed gastric emptying. This is due to EBV neurotropic properties, where it can affect the autonomic nervous system, particularly the vagal nerve and the enteric nervous system, both of which are essential for coordinating normal gastric motility. Therefore infection can lead to impaired contractions and delayed emptying. 

 

Additionally, EBV may trigger immune-mediated gastric dysfunction through persistent low-grade mucosal inflammation, characterized by cytokine overexpression and T-cell infiltration, which can disrupt neuromuscular coordination [13]

 

Dysbiosis 

 

Evidence suggests that the microbiome of the duodenum, the first part of the small intestine following the stomach, plays a pivotal role in the pathogenesis of FD. Patients with FD often exhibit increased levels of pro-inflammatory bacteria, such as Streptococcus, Staphylococcus and Clostridium, which can produce enterotoxins that provoke low-grade inflammation. In parallel, there is often a loss of beneficial bacteria which normally support anti-inflammatory activities that support maintenance of mucosal integrity.[22]

 

FD patients also frequently display duodenal infiltration by immune cells, such as eosinophils and mast cells, which can release inflammatory mediators that sensitize enteric nerves, induce pain, and disrupt gastric motility. Emerging evidence suggests that these immune changes may be driven by dysbiosis, as certain bacterial species associated with FD are known to trigger immune responses.[21]

 

Furthermore, dysbiosis influences gut-brain communication through neuroimmune signaling, hormonal pathways, and microbial metabolites. An imbalanced duodenal microbiota can alter the production of key neuromodulators, which play crucial roles in gastrointestinal sensations, which can in turn heighten visceral hypersensitivity, and ultimately exacerbate the severity of FD symptoms.[22]

 

Candidiasis  

 

In a clinical study involving 111 individuals, including both healthy participants and those with dyspeptic symptoms, Candida albicans was found to be 40% more prevalent among those with dyspepsia. Notably, a specific genetic variant of C. albicans, known as DST1593, which exhibits a stronger ability to colonize the gastric mucosa, and was detected in 60% of dyspeptic patients, compared to just 15% of healthy individuals.[23]

 

Protozoa Infection: Giardia 

 

Protozoal parasitic infections, particularly Giardia, have been implicated in the development of functional dyspepsia. During acute giardiasis, the parasite adheres to the section of the intestines directly after the stomach, leading to epithelial damage and villous atrophy. Even after successful eradication of the parasite, these mucosal alterations may persist, contributing to chronic low-grade inflammation, immune dysregulation, and visceral hypersensitivity, all of which are key mechanisms in FD pathophysiology. 

 

Additionally, Giardia-induced disruption of gut-brain axis signaling and alterations in the microbiota may further impair gastric motility and sensory function. These changes help explain why some patients continue to experience dyspeptic symptoms long after the acute infection has resolved [4]
 

High Histamine [ Mast Cell Activation ] 

 

Mast Cell Activation involves the release of inflammatory chemicals such as histamine, which inappropriately, triggering chronic, multi-system symptoms, often including nausea, bloating, early fullness, and upper abdominal discomfort that closely mimic FD.

 

In a large study of over 2,000 participants with functional gastrointestinal disorders, including both IBS and FD, 85% showed symptoms consistent with a possible Mast Cell Activation. These mast cell-driven symptoms are often overlooked, leading to delays in diagnosis and ineffective treatment with medications for FD, highlighting the need for targeted mast cell therapy in applicable patients. [16][17]

 

Irritable Bowel Syndrome (IBS)

 

IBS and FD commonly coexist, with studies suggesting up to 40% overlap. IBS-related motility abnormalities and visceral sensitivity may extend to the upper GI tract, resulting in symptoms like postprandial fullness, bloating, and nausea [2][4][5].
 

Gallbladder Removal 

 

Gastric Accommodation is the stomach’s ability to relax and expand in response to a meal, and is critical for a healthy well functioning stomach. After gallbladder removal the continuous and unregulated flow of bile into the small intestine may disrupt normal digestive signaling and alter vagal reflexes, potentially interfering with gastric accommodation. This disruption can exacerbate or trigger FD symptoms in susceptible individuals. [4].
 

Diet + Lifestyle:

 

• High Fat Foods: The presence of fats in the duodenum triggers bile acid release, in order to digest fat, which is ordinarily asymptomatic. However, in patients with FD, fatty foods can exacerbate symptoms due to increased duodenal sensitivity, and acid exposure aggravation, which provokes the symptoms associated with FD [4].

 

• Caffeine: Caffeine stimulates gastric acid secretion and may worsen epigastric pain. [4]

 

• Alcohol: Alcohol irritates the gastric mucosa and stimulates acid production. Chronic intake contributes to gastritis, mucosal barrier breakdown, and inflammatory signaling activation, which can exacerbate FD. Alcohol also impairs gastric motility, slows emptying, and can affect vagal regulation[4][5]

 

• Food Poisoning: Food Poisoning infections are a well-established consequence of bacterial gastroenteritis. This can cause up to 30% of FD cases, with mechanisms involving mucosal inflammation, disruption of barrier integrity, and enteric nerve sensitization. [4][9]

 

• Intolerances: Food intolerances, such as reactions to gluten or dairy can provoke dyspeptic symptoms in the absence of structural disease. The mechanism likely involves gut-brain axis responses and immune activation [5].

 

• Smoking: Smoking is associated with mucosal damage, worsening ulcer risk, and may impair gastric healing [4].

 

Medications:

 

• NSAIDs: NSAIDs such as Ibuprofen, Aspirin and Diclofenac, amongst others, impair prostaglandin production, compromise gastric mucosal integrity, and are a leading cause of gastritis and ulcerations that contribute to Dyspepsia  [5][6].

 

• ADHD Medications: Methylphenidate based ADHD medications, such as Ritalin significantly increases the risk of certain gastrointestinal adverse events that mi. Specifically, it is associated with a 266% increased risk of decreased appetite and increases the likelihood of abdominal pain by about 61% [14]