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Physicians Gastrointestinal Imbalance & Chronic Disease

The gut is home to trillions of bacteria and other microbes (the gut microbiota) that support digestion and absorption of food, regulate the integrity and function of the gut lining, train and modulate the immune system, and communicate with the brain about energy uptake (via hormones and neurotransmitters) to affect mood and overall well-being.

When healthy and balanced, this ecosystem protects the body against infection while preventing tissue-damaging inflammatory responses to bacterial and foreign food antigens. Disturbance of this homeostatis in the gut is associated with many chronic diseases, at least partly stemming from immune system dysregulation triggered by infections, food sensitivity, maldigestion/malabsorption of food, intestinal dysbiosis, and/or intestinal permeability.

In fact, most functional gastrointestinal disorders including irritable bowel syndrome (IBS) comprise a number of different, often treatable, conditions that can be diagnosed or ruled out with the use of serum and fecal biomarkers.1-3 Such biomarkers give important clues into the underlying causes, information critical to the ability to effectively treat the disorder and restore the patient (and their gut) to a state of health, by means of dietary interventions, specific supplements, medications, and/or more targeted tests.

Salveo Diagnostics has created a streamlined program that incorporates scientifically supported, evidence-based tests along with an intuitive and informative lab report and professionally-trained clinical health educators, to help you personalize diagnosis and tackle this growing challenge head on. Our Gut Health Assessment will provide clinical information to help you treat the underlying cause of the disease rather than just the symptoms. The tests assess several broad areas of potential dysfunction:


Intestinal Dysbiosis

Dysbiosis is an undesirable shift in the composition of the microbiota that can lead to a plethora of chronic diseases if left unchecked.4,5 However,  potentially harmful microbes may coexist peacefully with beneficial ones if the overall balance of the microbiome is healthy. A high-fat, high-sugar (standard Western) diet may induce dysbiosis in the gut through the actions of bile which can affect the growth of some microbes. Chronic dysbiosis can alter the environment (e.g., pH) in the gut and thus invite pathogenic bacteria, fungi, or parasites to flourish. This can result in lower levels of beneficial bacteria, promoting intestinal hyperpermeability (“leaky gut”) and inflammation.

Firmicutes/Bacteroidetes Ratio                       Provides an estimate of the predominance of major phyla of gut bacteria; associated with dysbiosis and metabolic disorders.6

Short Chain Fatty Acids                                     Markers of dietary fiber fermentation in the gut; important for health of intestinal mucosa and protection against dysbiosis.7
(n-butyrate, propionate, acetate) 

 
Maldigestion/Malabsorption/Malnutrition

Maldigestion of food can cause GI symptoms such as bloating, abdominal pain, gas, constipation, or diarrhea, and can stem from issues such as low stomach acid, abnormal gut motility (either rapid or slow transit times), lack of bile acids, and exocrine pancreatic insufficiency (reduced secretion of digestive enzymes from the pancreas).8 Chronic maldigestion can promote bacterial/fungal overgrowth, which can compromise the intestinal barrier, allowing toxins, bacteria, and undigested food particles to enter the circulation and increase risk for food allergies, autoimmune disorders, and an overburdened liver.9

Malabsorption of nutrients can be a consequence of maldigestion and can also occur when infection or inflammation damages the intestinal mucosa or increases transit times.8 The resulting nutrient deficiencies can lead to other health complications such as anemia, skin and cognitive/mood disorders, impaired vision, and osteoporosis.10

Pancreatic Elastase        A pancreas-specific protease that passes unchanged through the intestine; an excellent marker of exocrine pancreatic insufficiency.11

Lipase                               Pancreatic enzyme for the digestion of dietary fat; marker of pancreatitis.12

Amylase                            Pancreatic enzyme for the digestion of dietary starch; marker of pancreatitis.12                                   

Prealbumin                       A prealbumin (transthyretin) test is often ordered to assess nutritional status and metabolic stress, and to help diagnose protein malnutrition or 
                                           underlying disease severity in patients with chronic illness.13

Vitamin D                          Vitamin D deficiency is associated with gut inflammation, autoimmunity, and increased susceptibility to GI disorders (e.g., colorectal cancer, IBD,                                                        diverticulitis, and IBS).14,15 Low serum vitamin D is linked to higher risk and severity of intestinal malabsorption syndromes (e.g., IBD and celiac                                                          disease).14

Gut Inflammation

Dysregulation of the normal homeostatic relationships between the gut microbiota and host immune system can lead to intestinal inflammation, and evidence suggests that luminal flora may be a central factor in the development of inflammatory bowel disease (IBD).16 Crohn’s disease and ulcerative colitis are immune-mediated conditions characterized by chronic inflammation of the small and large intestine.  The pathogenesis of these conditions is multifactorial, but they are generally thought to result from “an exaggerated immune response towards the gut microbiome/toxic luminal substances in a genetically susceptible individual.”17 

Possible triggers may include:

Candida (yeast) overgrowth — intestinal dysbiosis (imbalance) favoring yeast overgrowth disrupts the intestinal epithelium, causing hyperpermeability
Certain medications — chronic use of drugs such as antibiotics, aspirin, acid-reducing drugs, or nonsteroidal anti-inflammatory drugs (NSAIDs)
Food additives and inflammatory foods — gluten, emulsifiers, excess sugar/alcohol consumption, and dairy
Stress and age

Calprotectin                                    A neutrophil-derived calcium-binding protein, calprotectin is a highly sensitive and specific marker for intestinal neutrophil activity and 
                                                          gastrointestinal inflammation; can be used for distinguishing IBD from IBS.18

Eosinophil-Derived Neurotoxin    A glycoprotein that is released from eosinophil granulocytes, commonly in allergic response to certain foods or intestinal parasites.                                                                            Increased fecal levels may reflect infection, inflammation, and/or severity of tissue damage.19,20

Secretory IgA                                  The major antibody produced in tears, saliva, and the intestinal mucosa in response to harmful or antigenic substances. Elevated fecal levels 
                                                          may indicate an upregulated immune response in the intestinal mucosa. Low sIgA can signal chronic stress in the GI tract and can be a factor                                                           in the development of food allergy or intolerance. 21

Vitamin D                                         Vitamin D deficiency is associated with gut inflammation, autoimmunity, and increased susceptibility to GI disorders (e.g., colorectal cancer,
                                                           IBD, diverticulitis, and IBS).14,15  Low serum vitamin D is also linked to higher risk and severity of intestinal malabsorption syndromes (e.g.,                                                                   IBD and celiac disease).15

C-reactive protein (hs-CRP)           A nonspecific acute-phase protein whose serum levels can be elevated in response to inflammation, infection, or tissue injury.22

Intestinal Permeability

The permeability of the intestinal epithelium is finely regulated by the presence of tight junctions—molecular complexes that seal the spaces between the epithelial cells, guiding passage of select molecules (e.g., nutrients) through the transcellular spaces. The epithelial cells produce mucus and antimicrobial molecules to further protect against toxins or infectious agents. Breakdown of this barrier can cause a disruption of normal mucosal immune homeostasis and uncontrolled inflammation, allowing increased passage of undigested food particles, microorganisms, and their immune-stimulating antigenic products (e.g., lipopolysaccharide) into the circulation.23 The integrity  of the epithelial cells themselves can also affect intestinal barrier function; if disrupted, tight-junction components and regulatory proteins will appear in the stool.

Zonulin                                           A protein that modulates the permeability of tight junctions between cells of the wall of the digestive tract and can be elevated due to 
                                                        microbial overgrowth or food triggers (e.g., gluten). Because elevated zonulin signifies impaired gut barrier function, healing the gut lining is                                                                key to preventing systemic entry of antigens, inflammation, and autoimmunity.24

Gastrointestinal Bleeding

The immunochemical fecal occult blood test (iFOBT) detects the presence of hidden blood in the stool, which may indicate a benign or cancerous growth, IBD, or other damage to the gut lining.25,26

Immunochemical Fecal Occult  Blood Test (iFOBT)        Hidden blood in the stool could indicate benign or malignant polyps, ulcers, or inflammatory bowel diseases.     

Gastrointestinal Pathogens

Intestinal parasites, pathogenic bacteria, and viruses can be a significant source of GI illness.27 If the immune system does not manage to clear them or keep them in check, they may start to cause patient symptoms. We perform immunoassays for H. pylori Antigen and Blastocystis spp. Antigens, and molecular diagnostic tests for the following common pathogenic causes of infectious gastroenteritis.28                                       

Parasites                                           Cryptosporidium spp.,  Cyclospora cayetanensusGiardia lamblia, Entamoeba histolytica

Bacteria and Bacterial Toxins        Campylobacter spp., C. difficile (toxin A/B), Plesiomonas shigelloidesE. coli O157, Enteroaggregative E. coli (EAEC), Enteropathogenic E.                                                                   coli  (EPEC), Enterotoxigenic E. coli (ETEC), Shiga-toxin-producing E. coli  (STEC),  SalmonellaShigella/Enteroinvasive E.                                                                                                  coli (EIEC),  Vibrio spp., Vibrio cholerae cholera toxin gene (ctx), Yersinia enterocolitica

Viruses                                               Adenovirus F40/41, Astrovirus, Norovirus GI/GII, Rotovirus A, Sapovirus (I, II, IV, and V)

Systemic Autoimmunity

Autoimmune disorders are often triggered or made worse in genetically susceptible individuals by intestinal dysbiosis and a dysregulated gut inflammatory response (often with increased intestinal permeability) to stress, toxins, infections, nutrient insufficiencies, and various foods.29,30

Antinuclear Antibodies by IFA        Antinuclear antibodies (ANA) are a key feature of systemic or other autoimmune conditions.31,32 This test has high negative predictive value 
                                                            for ruling out suspected connective tissue disorders.33 The presence of ANA in asymptomatic patients may indicate subclinical  
                                                            autoimmunity and/or increased  risk for future autoimmune disease.34

Yeast Detection

While the human microbiota is made up mostly of bacterial species, everybody carries some fungal species too — a much smaller component of the microbiota, separately referred to as the “mycobiota.”35,36 In healthy individuals, these fungi cause no problem. However, when the gut microbiota is upset by antibiotics, chemotherapy, or immunosuppressive drugs, or the immune system is compromised, certain fungi can become opportunistic and pathogenic. Diseases caused by overgrowth of indigenous yeast species, such as Candida albicans (C. albicans), are a significant cause of illness and death in critical care settings, and also play a significant role in a growing number of chronic diseases affecting the general population.36

Yeast Culture                                              Semi-quantitative, accurate, and rapid identification of yeast in the stool (Candida albicans and other Candida species versus non-                                                                               Candida species) using microbiological and colorimetric enzymatic methods.37,38

Anti-Candida Antibodies                          High titers may indicate opportunistic Candida overgrowth, intestinal dysbiosis, and damage to the gut lining, often exacerbated                                                                                   by immune system depletion, certain medications, metabolic disease, or sugar-rich diet.37,

Celiac Disease Antibodies

Celiac disease or gluten-sensitive enteropathy is an autoimmune disorder characterized by chronic inflammation of the small-intestinal mucosa in response to ingested gluten (the storage protein of wheat, rye, and barley) in genetically predisposed individuals.39 In this condition, undigested gliadin peptides—the toxic component of gluten—leak through the intestinal barrier, where they are deamidated by tissue transglutaminase (tTG) to form deamidated gliadin peptides (DGP), triggering an inflammatory immune reaction in the process.

Anti-tTG (IgA and IgG)                                 Tissue transglutaminase antibodies are highly sensitive and specific for the diagnosis of celiac disease.40

Anti-DGP (IgA and IgG)                               Combined testing for anti-tTG and anti-DGP (deamidated gliadin peptides) provides the best diagnostic accuracy for celiac disease.40

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