Latest Review Date: January 2024

Category:  Laboratory/Pathology                                         

POLICY:

Fecal analysis of the following components is considered investigational as a diagnostic test for the evaluation of intestinal dysbiosis, irritable bowel syndrome, malabsorption, or small intestinal overgrowth of bacteria:

• Triglycerides
• Chymotrypsin
• ISO-butyrate, ISO-valerate, and n-valerate
• Meat and vegetable fibers
• Long chain fatty acids
• Cholesterol
• Total short chain fatty acids
• Levels of Lactobacilli, bifidobacteria, and Escherichiacoli and other “potential pathogens,” including Aeromonas, Bacillus cereus, Campylobacter, Citrobacter, Klebsiella, Proteus, Pseudomonas, Salmonella, Shigella, Staphylococcus aureus, and Vibrio
• Identification and quantitation of fecal yeast (including Candida albicans, Candida tropicalis, Rhodotorula, and Geotrichum)
• N-butyrate
• Beta-glucuronidase
• pH
• Short chain fatty acid distribution (adequate amount and proportions of the different short chain fatty acids reflect the basic status of intestinal metabolism)
• Fecal secretory IgA

DESCRIPTION OF PROCEDURE OR SERVICE:

Intestinal dysbiosis may be defined as a state of disordered microbial ecology that is believed to cause disease. Laboratory analysis of fecal samples is proposed as a method of identifying individuals with intestinal dysbiosis and other gastrointestinal disorders.

Fecal Markers of Dysbiosis

Laboratory analysis of both stool and urine has been investigated as markers of dysbiosis. Commercial laboratories may offer testing for comprehensive panels or individual components of various aspects of digestion, absorption, microbiology, and metabolic markers. Representative components of fecal dysbiosis testing are summarized in Table 1.

Table 1. Components of the Fecal Dysbiosis Marker Analysis

a Fecal calprotectin as a stand-alone test not addressed in this policy.

A related topic, fecal microbiota transplantation (FMT), the infusion of intestinal microorganisms to restore normal intestinal flora is not addressed in this policy. FMT has been rigorously studied for the treatment of patients with recurrent Clostridioides difficile infection.

KEY POINTS:

The most recent literature review was updated through October 24, 2023.

Summary of Evidence

For individuals with gastrointestinal conditions such as suspected intestinal dysbiosis, irritable bowel syndrome (IBS), malabsorption, or small intestinal bacterial overgrowth who receive fecal analysis testing, the evidence includes several cohort and case-control studies comparing fecal microbiota in patients who had a known disease with healthy controls. Relevant outcomes are test validity, symptoms, and functional outcomes. The available retrospective cohort studies on fecal analysis have suggested that some components of the fecal microbiome and inflammatory markers may differ across patients with IBS subtypes. No studies were identified on the diagnostic accuracy of fecal analysis versus another diagnostic approach or that compared health outcomes in patients managed with and without fecal analysis tests. No studies were identified that directly informed the use of fecal analysis in the evaluation of intestinal dysbiosis, malabsorption, or small intestinal bacterial overgrowth. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

American Gastroenterological Association

The American Gastroenterological Association (AGA) published clinical practice guidelines (2019) on laboratory evaluation of functional diarrhea and diarrhea-predominant irritable bowel syndrome (IBS) in adults. Related to fecal analysis, the AGA suggests the use of fecal calprotectin or fecal lactoferrin to screen for IBS in individuals presenting with chronic diarrhea (conditional recommendation; low-quality evidence).

In 2020, the AGA published a clinical practice update on small intestinal bacterial overgrowth (SIBO). On the topic of fecal analysis, the guideline states, "there is insufficient evidence to support the use of inflammatory markers, such as fecal calprotectin to detect SIBO." No other fecal markers are explicitly mentioned.

U.S. Preventive Services Task Force Recommendations

No U.S. Preventive Services Task Force (USPSTF) recommendations have been identified.

KEY WORDS:

Comprehensive Digestive Stool Analysis 2.0, Fecal Analysis, Intestinal Dysbiosis, Genova Diagnostics, Stool Analysis, comprehensive stool analysis, The Gastrointestinal Microbial Assay Plus (GI-MAP)

APPROVED BY GOVERNING BODIES:

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). Laboratories that offer laboratory-developed tests must be licensed by the CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of comprehensive testing for fecal dysbiosis.

Some U.S commercially available fecal dysbiosis tests are listed below in Table 2.

Table 2. Commercially Available Fecal Dysbiosis Tests by CLIA Certified Laboratories

CLIA: Clinical Laboratory Improvement Amendments

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP:  Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING:

CPT Codes:

The following CPT codes may be used to identify individual components of fecal analysis of intestinal dysbiosis:

REFERENCES:

1. Andoh A, Kuzuoka H, Tsujikawa T et al. Multicenter analysis of fecal microbiota profiles in Japanese patients with Crohn's disease. J Gastroenterol 2012; 47(12):1298-307.
2. Collins SM, Denou E, Verdu EF, et al. The putative role of the intestinal microbiota in the irritable bowel syndrome. Dig Liver Dis 2009; 41(12):850-3.
3. De Palma G, Nadal I, Medina M et al. Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiology 2010; 10: 63.
4. Emmanuel A, Landis D, Peucker M, et al. Faecal biomarker patterns in patients with symptoms of irritable bowel syndrome. Frontline Gastroenterol. Oct 2016; 7(4):275-282.
5. Genova Diagnostics. 2022; https://www.gdx.net/tests/prep/gi-stool-profiles. Accessed October 26, 2022.
6. Genova Diagnostics. 2023; https://www.gdx.net/tests/prep/gi-stool-profiles.
7. Goepp J, Fowler E, McBride T, et al. Frequency of abnormal fecal biomarkers in irritable bowel syndrome. Glob Adv Health Med. May 2014; 3(3):9-15.
8. Hoveyda N, Heneghan C, Mahtani KR, et al.  A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome.  BMC Gastroenterol 2009; 9:15.
9. Hungin AP, Mulligan C, Pot B et al. Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice -- an evidence-based international guide. Aliment Pharmacol Ther 2013; 38(8):864-86.
10. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
11. Jeffery IB, Das A, O'Herlihy E, et al. Differences in Fecal Microbiomes and Metabolomes of People With vs Without Irritable Bowel Syndrome and Bile Acid Malabsorption. Gastroenterology. Mar 2020; 158(4): 1016-1028.e8.
12. Jonkers D, Penders J, Masclee A et al. Probiotics in the management of inflammatory bowel disease: a systematic review of intervention studies in adult patients. Drugs 2012; 72(6):803-23.
13. Joossens M, Huys G, Cnockaert M et al. Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut 2011; 60(5):631-7.
14. Langhorst J, Elsenbruch S, Koelzer J et al.  Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel disease: performance of fecal lactoferrin, calprotectin, and PMN-Elastase, CRP and clinical indices.  Am J Gasteroenterol 2008; 103(1):162-9.
15. McFarland LV and Dublin S.  Meta-analysis of probiotics for the treatment of irritable bowel syndrome.  World J Gastroenterol 2008; 14(17):2650-61.
16. Nikfar S, Rahimi R, Rahimi F et al. Efficacy of probiotics in irritable bowel syndrome: a meta-analysis of randomized, controlled trials. Dis Col Rectum 2008; 51(12):1775-80.
17. Otten CM, Kok L, Witteman BJ et al.  Diagnostic performance of rapid tests for detection of fecal calprotectin and lactoferrin and their ability to discriminate inflammatory from irritable bowel syndrome.  Clin Chem Lab Med 2008; 46:1275-80.
18. Pimentel M, Chow EJ and Lin HC.  Eradication of small intestinal bacterial overgrowth reduces symptoms of irritable bowel syndrome.  Am J Gastroenterol 2000; 95(12):3503-6.
19. Quigley EMM, Murray JA, Pimentel M. AGA Clinical Practice Update on Small Intestinal Bacterial Overgrowth: Expert Review. Gastroenterology. Oct 2020; 159(4): 1526-1532.
20. Schoepfer AM, Trummler M, Seeholzer P et al. Discriminating IBD from IBS: comparison of the test performance of fecal markers, blood leukocytes, CRP, and IBD antibodies. Inflamm Bowel Dis 2008; 14:32-9.
21. Smalley W, Falck-Ytter C, Carrasco-Labra A, et al. AGA Clinical Practice Guidelines on the Laboratory Evaluation of Functional Diarrhea and Diarrhea-Predominant Irritable Bowel Syndrome in Adults (IBS-D). Gastroenterology. Sep 2019; 157(3): 851-854. 
22. Sobhani I, Tap J, Roudot-Thoraval F et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One 2011; 6(1):e16393.
23. Tana C, Umesaki Y and Imaoka A.  Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome.  Neurogastroenterol Motil 2010 May; 22(5):512-9.
24. Vanner SJ, Depew WT, Paterson WG, et al.  Predictive value of the Rome criteria for diagnosing the irritable bowel syndrome.  Am J Gastroenterol 1999; 94(10):2912-7.
25. Walters B and Vanner SJ.  Detection of bacterial overgrowth in IBS using the lactulose H2 breath test: Comparison with 14C-D-xylose and healthy controls.  Am J Gastroenterol 2005; 100(7):1566-70.
26. Whorwell PJ, Altringer L, Morel J, et al.  Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome.  Am J Gastroenterol 2006; 101(7):1581-90.
27. Wilhelm SM, Brubaker CM, Varcak EA, et al.  Effectiveness of probiotics in the treatment of irritable bowel syndrome.  Pharmacotherapy 2008; 28(4):496-505.

POLICY HISTORY:

Medical Policy Group, February 2010 (2)

Medical Policy Administration Committee, February 2010

Available for comment February 23-April 8, 2010

Medical Policy Panel, February 2010

Medical Policy Group, June 2010 (2): Key Points and References updated

Medical Policy Panel, February 2013

Medical Policy Group, February 2013 (2): 2013 Updates to Key Points and References; no change in policy statement

Medical Policy Panel, February 2014

Medical Policy Group, February 2014 (1): Update to Key Points and References; no change in policy statement

Medical Policy Panel, February 2015

Medical Policy Group, February 2015 (3):  2015 Update to Key Points and References; no change in policy statement.

Medical Policy Group, November 2015:  2016 Annual Coding Update; added CPT code 82542 to current coding. Created previous coding section and moved CPT code 82491 from current coding to previous coding.

Medical Policy Panel, December 2015

Medical Policy Group, January 2016 (3): Updates to Description, Key Points, and Approved Governing Bodies; moved deleted CPT code 82492 from current coding to previous coding.

Medical Policy Panel, December 2016

Medical Policy Group, December 2016 (3): 2016 Updates to Description, Key Points, Key Words & References; no change in policy statement

Medical Policy Panel, December 2017

Medical Policy Group, January 2018 (3): 2017 Updates to Description and Key Points; no new references added; no change in policy statement.

Medical Policy Panel, December 2018

Medical Policy Group, January 2019 (9): Updates to Description, Key Points, Approved by Governing Bodies, and References.  No change to policy statement.

Medical Policy Panel, December 2019

Medical Policy Group, December 2019 (9): 2019 Updates to Description, Key Points. Deleted Previous Coding Section Dated 2016. Added code 82271 to Current Coding Section. No change to policy statement.

Medical Policy Panel, December 2020

Medical Policy Group, December 2020 (9): 2020 Updates to Description, Key Points, References (updated references, no new references added). No change to policy statement.

Medical Policy Panel, December 2021

Medical Policy Group, December 2021 (9): 2021 Updates to Description, Key Points, References. Removed CPT code 82656 from policy. Policy statement updated to remove “not medically necessary,” no change to policy intent.

Medical Policy Panel, December 2022

Medical Policy Group, December 2022 (9): 2022 Updates to Description, Key Points, References. No change to policy statement.

Medical Policy Panel, December 2023

Medical Policy Group, January 2024 (5): Updates to Description, Key Points, Approved by Governing Bodies, Benefit Application, and References. No change to Policy Statement.

Medical Policy Group, March 2024 (5): Update to Key Words to include: The Gastrointestinal Microbial Assay Plus (GI-MAP). No change to Policy Statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.