PLMI Blog

Understanding the intricate interactions between various physiological systems is paramount for comprehending the root cause of health issues and devising effective treatment strategies. Much like a highway system engineered to allow multi-directional travel carrying goods and services, information, and waste between suburban neighborhoods and a central city hub, the digestive system relies on interactions with the nervous, endocrine, immune, and hepatobiliary systems to create a digestive supersystem (1).

A complex communication network utilizing biochemical agents, electrical signaling, and molecular messaging throughout the digestion supersystem supports the body in optimally digesting food, absorbing and assimilating nutrients, protecting against pathogens, and detoxifying harmful substances. When one or more peripheral systems experience dysfunction, digestion suffers, and gastrointestinal (GI) disorder symptoms may present in a patient in days, weeks, months, or even years after the complementary system breaks down (2). Disruptions in the balance of the GI microbiome are common occurrences when the digestive supersystem does not function as it should and fails to properly host the symbiotic species residing in the gut (3).

Effective clinical management of upper- and lower-GI dysfunction entails symptom recognition beyond the intestinal manifestations of diarrhea and constipation commonly reported in cases of irritable bowel disease (4). Detailed patient history-taking, including dietary habits, lifestyle factors, medication use, past medical history, and family history of GI disorders and related peripheral system signs, provides valuable insights into potential triggers and predisposing factors. Symptom analysis, including the nature, severity, duration, and timing of GI symptoms such as abdominal pain, bloating, diarrhea, constipation, reflux, and changes in bowel habits, helps elucidate the underlying pathology. When possible, a thorough physical examination focusing on abdominal assessment, looking for tenderness, distension, organomegaly, and abnormal bowel sounds, provides additional diagnostic clues. Examination of extra-abdominal signs, such as oral ulcers (5), dermatological manifestations (6), and signs of nutritional deficiencies (7), may also be informative in certain GI disorders. A keen eye for signs and symptoms along the side roads of the digestive supersystem highway will lead providers to root cause solutions and a holistic treatment approach to GI disease.

Many Roads Lead to the Digestion Supersystem Highway

Nervous System Interaction:  The digestive system maintains close communication with the nervous system, locally and centrally, to regulate digestive processes.

• The enteric nervous system (ENS), often referred to as the “second brain,” is a complex network of neurons within the digestive tract that locally regulates various digestive functions independently of the central nervous system (CNS) (8). However, the CNS significantly influences the ENS through the Sympathetic and Parasympathetic nerve branches. At the same time, the GI microbiome plays a role in the development and function of both the ENS and CNS (9).
• Centrally, the CNS regulates the secretion of digestive juices, controls peristalsis, and triggers the release of hormones that affect digestion and absorption (10).
• Dysregulation in the autonomic nervous system (ANS), often due to chronic stress or autonomic dysfunction, can lead to altered gastrointestinal motility, visceral hypersensitivity, and increased gut permeability, contributing to digestive disorders like irritable bowel syndrome (IBS) and functional dyspepsia (10).

Endocrine System Interaction:  Hormonal signaling from various endocrine glands, such as the stomach, pancreas, and small intestine, acts on target cells within the digestive tract to modulate digestive functions.

• The hormones gastrin, secretin, cholecystokinin (CCK), ghrelin, and insulin are intricately involved in regulating gastric acid secretion, pancreatic enzyme release, bile production and release, appetite stimulation, and glucose metabolism, respectively (11).
• Dysregulation in these hormonal pathways (often influenced by dietary factors, gut microbiota composition, and metabolic imbalances) can lead to metabolic syndrome, obesity, diabetes, gastrointestinal disorders like gastroesophageal reflux disease (GERD), and gallstone formation (11).

Immune System Interaction:  The digestive system is routinely exposed to potential pathogens and foreign antigens from food and the environment. The GI tract maintains a delicate balance between immune tolerance and immune defense against pathogens.

• The gut-associated lymphoid tissue (GALT), including Peyer’s patches and lymphoid follicles in the intestines, and the mucosal-associated lymphoid tissue (MALT) of the gastrointestinal endothelium, serve as crucial sites for immune surveillance and response within the digestive tract (12).
• Disruptions in gut barrier integrity, dysbiosis (imbalance in gut microbiota), and chronic low-grade inflammation can trigger immune-mediated disorders like inflammatory bowel disease (IBD), celiac disease, and food sensitivities (13).
• Immune cells such as macrophages, dendritic cells, and lymphocytes are present throughout the digestive system to detect and neutralize pathogens, preventing infections and maintaining gut homeostasis (14).

Hepatobiliary System Interaction: Comprised of the liver, gallbladder, and bile ducting pathways, the hepatobiliary system plays essential roles in digestion, nutrient absorption, metabolic regulation, and detoxification.

• The liver synthesizes bile to be stored and concentrated in the gallbladder. Upon release into the small intestine, bile becomes crucial for lipid digestion, fatty acid and fat-soluble vitamin absorption, and detoxifying harmful substances (15).
• Disruptions in hepatic bile synthesis, intestinal peristalsis and permeability, and mucosal receptor activity can affect the quantity and quality of bile acids, increasing the risk of extrahepatic pathologies (16).
• Dysfunction in the hepatobiliary system, often linked to poor dietary choices, excess alcohol consumption, toxin exposure, and metabolic disorders, can lead to impaired bile flow, gallstone formation, non-alcoholic fatty liver disease (NAFLD), and dysregulated lipid metabolism (17).

Understanding these intricate subsystem interactions with the digestive system allows clinicians to adopt a functional approach to assessing and addressing digestive health issues. By addressing underlying factors such as diet, lifestyle, stress management, gut microbiota balance, and metabolic health, they can promote optimal digestive function and overall well-being in their patients.

Repairing Significant Problems Generated by Digestive Supersystem Dysfunction

Advances in microbiome understanding have revolutionized assessing and managing upper- and lower-GI system disorders. Here’s how.

Upper Gastrointestinal Disorders:

Gastric Ulcers and Helicobacter pylori (H. pylori) Infection: The discovery of H. pylori as a causative factor in gastric ulcers led to targeted antibiotic therapies drastically improving treatment outcomes (18). Understanding the role of hypochlorhydria and gut microbiome imbalance in modulating H. pylori colonization and gastric mucosal inflammation has spurred research into betaine hydrochloride and probiotics as adjunctive therapies to enhance H. pylori eradication rates and promote mucosal healing (19).

Gastroesophageal Reflux Disease (GERD): Dysbiosis is implicated in the pathogenesis of GERD. Probiotics and dietary interventions to restore microbial balance and improve gut barrier function have shown promise in alleviating GERD symptoms and reducing esophageal inflammation (20).

Lower Gastrointestinal Disorders:

Inflammatory Bowel Disease (IBD): The gut microbiome plays a critical role in the pathogenesis and progression of IBD, with dysbiosis implicated in immune dysregulation and chronic intestinal inflammation. Personalized microbiome profiling and metagenomic analysis have provided insights into microbial signatures associated with IBD subtypes, allowing for more targeted therapeutic interventions. Fecal microbiota transplantation (FMT), a procedure aimed at restoring gut microbial balance, has emerged as a promising therapy for select patients with refractory IBD, particularly recurrent Clostridioides difficile infection and ulcerative colitis (21).

Irritable Bowel Syndrome (IBS): Alterations in gut microbiota composition and function have been observed in individuals with IBS, contributing to gastrointestinal symptoms such as abdominal pain, bloating, and altered bowel habits (22). Probiotics, prebiotics, and dietary modifications targeting the gut microbiome have effectively alleviated IBS symptoms and improved quality of life (23). Advancements in microbial-based diagnostics, including breath tests and stool analysis, have facilitated the identification of specific microbial biomarkers associated with IBS subtypes, enabling more personalized treatment approaches (22, 23, 24).

Colorectal Cancer (CRC): Dysbiosis and microbial dysregulation have been implicated in colorectal carcinogenesis, influencing tumor initiation, progression, and response to therapy (25). Strategies aimed at modulating the gut microbiome, such as dietary interventions, probiotics, and FMT, hold the potential for mitigating CRC risk and improving treatment outcomes. Microbiome-based biomarkers may serve as diagnostic and prognostic indicators for CRC, guiding therapeutic decision-making and surveillance strategies (26).

Advances in microbiome research have provided unprecedented insights into the pathogenesis and management of upper and lower GI disorders. By leveraging this knowledge, clinicians can implement targeted interventions to restore microbial balance, alleviate symptoms, and improve outcomes for patients with GI conditions.

Functional Assessment Tools for Locating the Problems

Functional Laboratory Testing assesses various aspects of GI function:

• Comprehensive stool analysis to evaluate microbial balance, digestive enzyme activity, inflammation markers, and occult blood (27).
• Breath tests for detecting small intestinal bacterial overgrowth (SIBO), lactose intolerance, and other malabsorption syndromes (28).
• Food sensitivity testing to identify potential triggers of immune-mediated reactions and gut inflammation (29).
• Comprehensive metabolic panels to assess nutritional status, liver function, and metabolic imbalances (30).
• Genetic testing to identify genetic predispositions and susceptibilities to GI disorders, such as celiac disease and hereditary colorectal cancer syndromes (31).

Imaging Studies:

• Imaging modalities such as abdominal ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic procedures (esophagogastroduodenoscopy, colonoscopy) may be utilized to visualize structural abnormalities, mucosal lesions, strictures, and tumors (32).
• Capsule endoscopy and double-contrast barium studies are used for evaluating small bowel pathology not readily visualized by conventional endoscopy (33).

Microbiome Analysis:

• Microbiome analysis utilizing next-generation sequencing techniques provides insights into the gut microbiota’s composition, diversity, and functional capacity. Microbiome testing aids in identifying dysbiosis, microbial imbalances, and potential microbial contributors to GI disorders, guiding targeted interventions such as probiotics, prebiotics, and dietary modifications (34).

When the digestive supersystem highway degrades beyond the capacity of nutritional intervention to repair the communication processes, integrating these assessment techniques can help clinicians understand the underlying factors contributing to GI disorders, facilitating individualized treatment plans to restore gut health and promote overall well-being.

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Are you interested in learning more about the latest research on functional medicine tools for managing GI disorders? Join PLMI as we learn from the leading experts on this critical topic during the first of a two-part, free, live, virtual webinar “Advances in the Management of Gastrointestinal Disorders: Upper and Lower GI Issues and their Relationship to the Microbiome.” Part 1 will be held on March 19, 2024, from 5-7 pm PST and Part 2 on March 26, 2024, from 5-7 pm PST. Registration is FREE and takes just a minute using the following links: Register for Part 1 and Register for Part 2

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