It can be frustrating when you test negative for small intestinal bacterial overgrowth (SIBO) but still suffer from persistent gastrointestinal (GI) symptoms. However, the silver lining is that a negative SIBO test rules out one potential cause, bringing you closer to identifying the underlying issue. Before undergoing the SIBO test, you should have completed the test for intestinal methanogen overgrowth (IMO). With SIBO and, IMO ruled out, it’s time to explore other potential diagnoses. 

A negative SIBO breath test

According to the North American Consensus guidelines, a rise in hydrogen (≥20 ppm) in a breath test is considered positive for SIBO. If you have followed the preparation guidelines for hydrogen/methane breath testing (HMBT) – such as discontinuing antibiotics, promotility drugs, and laxatives and adhering to the required fasting period – a negative breath test generally means that SIBO is not the cause of your symptoms (1).  

If it’s not SIBO, what could it be?

It is now established that there is bidirectional communication between the central nervous system and the extensive network of nerves lining the gut (the enteric nervous system). This is known as the gut-brain axis (GBA), which links the brain’s thoughts and feelings to intestinal function (2). The GBA operates through complex signalling mechanisms that involve neural, immune, and hormone factors. Feeling emotional when you have an upset stomach, knowing when your stomach feels full, and recognising the need to go to the toilet are examples of the GBA system at work (3). Insights into the GBA axis have also led to the use of antidepressants for relieving GI symptoms, based on the idea that improving mood and reducing psychological distress can relieve gut discomfort (4). 

In the last blog, we described the roles of microorganisms residing throughout the GI tract – known as the gut microbiome – and how dysbiosis (an imbalance of beneficial and harmful microorganisms) is implicated in the development of neurological diseases, cancers, and immune deficiencies. Recent advances have confirmed the role of gut microbiota in influencing these gut-brain interactions and how excessive microbiome colonization can lead to disorders of the GBA (2).

There is emerging evidence to suggest that another potential cause of non-specific GI symptoms could be disorders of the GBA, which is estimated to affecting more than 40% of the population. The five most common disorders are irritable bowel syndrome (IBS), functional dyspepsia (chronic indigestion), functional constipation, functional diarrhoea, and functional bloating/distention (5). The term ‘functional’ indicates that although patients have ongoing symptoms, standard tests do not find any physical problems. It was once believed that these symptoms have no clear cause, but new understanding of the GBA has changed this perspective (6). 

GBA Disorders

The Rome criteria is currently the most widely accepted symptom-based, diagnostic methodology for GBA disorders (7). However, reaching a definitive diagnosis requires thorough history-taking supported by a comprehensive physical examination. Nuances in symptoms – such as onset (sudden vs gradual), duration (acute vs chronic), pain characteristics (location, quality, and continuous vs episodic), and accompanying symptoms (abdominal pain, nausea, bloating, and change in bowel habits) – as well as psychological and social factors that may be symptom-related need to be considered to reach a diagnosis (8). 

Figure 1. The microbiota-gut-brain axis is mediated through immune, nervous, and hormonal pathways. Impaired communication between the three parties can lead to disease onset (9).

Treatment of Gut Brain Axis Disorders

Dietary Interventions 

For those experiencing diarrhea-predominant symptoms, implementing a low-FODMAP diet can promptly and significantly improve diarrhea (10,11). FODMAPs are poorly-digested sugars that draw liquid into the intestines and promote bacterial fermentation, leading to excess gas, pressure build-up and diarrhea (12,13) A low-FODMAP diet is also suggested to improve abdominal pain, bloating, and quality of life for those with symptoms (14). Figure 2 summarizes foods that are high and low in FODMAP content (11). Following a low-FODMAP diet involves three steps (15). 

1. Restriction Phase: Adhere to the low-FODMAP diet as closely as possible for 6 weeks to assess its impact on GI symptoms.
2. Reintroduction Phase: Gradually reintroduce avoided foods one at a time, in increasing portions, to identify specific carbohydrates that cause symptoms.
3. Personalisation phase: Establish a personalized diet plan that includes both low-FODMAP foods and high-FODMAP foods that do not trigger symptoms.

Figure 2. Table of foods with high- and low-FODMAP content (16).

For those experiencing constipation-predominant symptoms, a fiber-rich diet can be effective in alleviating symptoms. Constipation is medically defined as difficult and infrequent bowel movements, typically characterized by having fewer than three bowel movements per week (17). You’ve probably heard that dietary fiber aids in bowel regularity, a fact supported by years of research, but do you know why (18)? First, let’s look into the different types of fiber. There are 2 main categories: soluble fiber (found in the inner flesh of fruits, most root vegetables, and legumes) and insoluble fibers (found in the outer skin of plants) (19). Insoluble fiber increases fecal mass and promotes food passage by stimulating the gut wall and peristalsis (the muscle contractions that propel food through the digestive tract). On the other hand, soluble fiber maintains the water content in stools, making them easier to pass (20). A combination of both fiber types is encouraged to improve constipation symptoms.

For those who do not have consistent bowel habits and struggle with both diarrhea and constipation along with other GI symptoms, treatment can be challenging. Mixed symptoms are multifactorial and there is yet to understand what conditions cause the symptoms to change. Ongoing research aims to uncover the various mechanisms behind changes in gut sensitivity, motility, and microbiome dysbiosis (21). Maintaining general well-being to limit microbiome overgrowth and dysbiosis is key. Patients are advised to:

• Eat regular meals with a healthy, balanced diet and adjust their fiber intake according to their symptoms.
• Maintain adequate fluid intake.
• Engage in 30 minutes of moderate-intensity physical activity at least 5 days a week.
• Identify and manage any stress, depression, or anxiety

Stress-reducing Interventions

Gut directed hypnotherapy:

Gut-directed hypnotherapy is a form of hypnosis focused on the digestive system. Through guided relaxation and calming imagery, it helps the gut “settle” and supports patients in learning self-hypnosis techniques to manage IBS symptoms. Studies show that around 70% of IBS patients respond, with relief lasting several years for many, and it may also help with anxiety and depression which is associated with IBS (22). In one trial, hypnotherapy produced improvements comparable to those seen with the low FODMAP diet over six months (23). 

In the UK, gut-directed hypnotherapy is available through some NHS gastroenterology centres, such as York and Manchester, or privately with qualified hypnotherapists following Professor Whorwell’s protocol. Courses are typically weekly over 6–12 weeks, and many patients continue using self-hypnosis at home afterwards. 

Cognitive Behavioural Therapy (CBT):  

Cognitive Behavioural Therapy (CBT) helps you identify and adjust patterns of thinking, behaviour, and emotion that can worsen IBS symptoms. IBS-focused CBT often includes relaxation techniques and strategies to reframe anxious thoughts, teaching skills to reduce “alarm” signals between the gut and the brain. 

Research shows that 60–70% of patients respond, with benefits lasting a year or more. CBT doesn’t cure IBS but can reduce the frequency and intensity of flare-ups, performing similarly to hypnotherapy. 

In the UK, CBT is available through NHS Talking Therapies (IAPT) via GP or self-referral. While IAPT often focuses on anxiety and depression, therapy can be adapted for IBS-related stress. Some regions also offer IBS group CBT or access through GI psychologists. It is best to speak to your doctor to find the best approach for you.  

Physical Therapies: Yoga & Exercise

Many people with IBS find that gentle physical activity can support symptom management. Yoga combines movement with relaxation and stress reduction. Certain poses may stimulate digestion in constipation or help calm the gut in diarrhoea. 

Evidence for yoga is mixed. Some small studies have shown improvements in IBS symptoms and anxiety, but larger analyses found no significant difference between yoga and control interventions for symptom severity or quality of life (24). Still, yoga is generally safe, may ease stress and muscle tension, and some people report it helps them feel better overall. 

You can read more about the connection between yoga and gut health in our dedicated blog post: Yoga for IBS. 

If the first-line dietary advice and lifestyle changes are ineffective, patients can consider referral to a clinician for further evaluation. In some cases, patients can be prescribed antimotility drug for persisting diarrhoea, laxatives for constipation or antispasmodic drug for ongoing abdominal pain and spasms (25).  Subsequent treatments are also likely to involve multidisciplinary groups with primary physicians, gastroenterologists, and specialist nutritionists.

How can OMED help

We understand that GI symptoms can be distressing and impact your quality of life. It’s important to be patient and give each change time to show results. We recommend implementing one change at a time and allowing it to take effect. The OMED app  can assist you in tracking your symptoms and any lifestyle changes to evaluate their effectiveness. Additionally, although you have tested negative for SIBO and IMO, these conditions can flare up, potentially worsening your symptoms. We suggest using the OMED Health Breath Analyzer to regularly monitor your hydrogen levels (used for SIBO diagnosis) and methane levels (used for IMO diagnosis). Still unsure? Book in a consultation appointment with an OMED Health doctor via the app. 

References

1. Rezaie A, Buresi M, Lembo A, Lin H, McCallum R, Rao S, et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. Am J Gastroenterol. 2017 May;112(5):775–84. doi: 10.1038/ajg.2017.46
2. Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol Q Publ Hell Soc Gastroenterol. 2015;28(2):203–9.
3. York and Scarborough Teaching Hospitals NHS Foundation Trust – Inflammatory Bowel Disease at York Hospital [Internet]. [cited 2024 Aug 21]. Available from: https://www.yorkhospitals.nhs.uk/our-services/a-z-of-services/inflammatory-bowel-disease-at-york-hospital/
4. Acharekar MV, Guerrero Saldivia SE, Unnikrishnan S, Chavarria YY, Akindele AO, Jalkh AP, et al. A Systematic Review on the Efficacy and Safety of Selective Serotonin Reuptake Inhibitors in Gastrointestinal Motility Disorders: More Control, Less Risk. Cureus. 14(8):e27691. doi: 10.7759/cureus.27691
5. Sperber AD, Bangdiwala SI, Drossman DA, Ghoshal UC, Simren M, Tack J, et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology. 2021 Jan;160(1):99-114.e3. doi: 10.1053/j.gastro.2020.04.014
6. Fikree A, Byrne P. Management of functional gastrointestinal disorders. Clin Med. 2021 Jan;21(1):44–52. doi: 10.7861/clinmed.2020-0980
7. Zhou Q, Verne GN. Are the Rome Criteria a Sound Standard for Gastrointestinal Disorders Worldwide? Gastroenterology. 2020 Apr 1;158(5):1212–4. doi: 10.1053/j.gastro.2020.02.016
8. Tome J, Kamboj AK, Loftus CG. Approach to Disorders of Gut-Brain Interaction. Mayo Clin Proc. 2023 Mar 1;98(3):458–67. doi: 10.1016/j.mayocp.2022.11.001
9. Loh JS, Mak WQ, Tan LKS, Ng CX, Chan HH, Yeow SH, et al. Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases. Signal Transduct Target Ther. 2024 Feb 16;9(1):1–53. doi: 10.1038/s41392-024-01743-1
10. Yoon SR, Lee JH, Lee JH, Na GY, Lee KH, Lee YB, et al. Low-FODMAP formula improves diarrhea and nutritional status in hospitalized patients receiving enteral nutrition: a randomized, multicenter, double-blind clinical trial. Nutr J. 2015 Nov 3;14:116. doi: 10.1186/s12937-015-0106-0
11. Guerreiro MM, Santos Z, Carolino E, Correa J, Cravo M, Augusto F, et al. Effectiveness of Two Dietary Approaches on the Quality of Life and Gastrointestinal Symptoms of Individuals with Irritable Bowel Syndrome. J Clin Med. 2020 Jan 2;9(1):125. doi: 10.3390/jcm9010125
12. Healthline [Internet]. 2018 [cited 2024 Aug 21]. FODMAP 101. Available from: https://www.healthline.com/nutrition/fodmaps-101
13. About FODMAPs and IBS | Monash FODMAP – Monash Fodmap [Internet]. [cited 2024 Aug 21]. Available from: https://www.monashfodmap.com/about-fodmap-and-ibs/
14. Schumann D, Klose P, Lauche R, Dobos G, Langhorst J, Cramer H. Low fermentable, oligo-, di-, mono-saccharides and polyol diet in the treatment of irritable bowel syndrome: A systematic review and meta-analysis. Nutrition. 2018 Jan 1;45:24–31. doi: 10.1016/j.nut.2017.07.004
15. Gentle low FODMAP diet [Internet]. Kent Community Health NHS Foundation Trust. [cited 2024 Aug 20]. Available from: https://www.kentcht.nhs.uk/leaflet/gentle-low-fodmap-diet/
16. Three step FODMAP Diet – Monash Fodmap [Internet]. [cited 2024 Aug 21]. Available from: https://www.monashfodmap.com/3_step_fodmap_diet/
17. nhs.uk [Internet]. 2017 [cited 2024 Aug 21]. Constipation. Available from: https://www.nhs.uk/conditions/constipation/
18. Yang J, Wang HP, Zhou L, Xu CF. Effect of dietary fiber on constipation: a meta analysis. World J Gastroenterol. 2012 Dec 28;18(48):7378–83. doi: 10.3748/wjg.v18.i48.7378
19. Akbar A, Shreenath AP. High Fiber Diet. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Aug 21]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK559033/
20. Di Rosa C, Altomare A, Terrigno V, Carbone F, Tack J, Cicala M, et al. Constipation-Predominant Irritable Bowel Syndrome (IBS-C): Effects of Different Nutritional Patterns on Intestinal Dysbiosis and Symptoms. Nutrients. 2023 Mar 28;15(7):1647. doi: 10.3390/nu15071647
21. Nee J, Lembo A. Review Article: Current and future treatment approaches for IBS with diarrhoea (IBS-D) and IBS mixed pattern (IBS-M). Aliment Pharmacol Ther. 2021 Dec;54 Suppl 1:S63–74. doi: 10.1111/apt.16625
22. Nation Health Service (NHS). Gut Directed Hypnotherapy For Brain Gut Axis Disorders [Internet]. York and Scarborough Teaching Hospitals NHS Foundation Trust.; 2007 [cited 2025 Nov 7]. Available from: http://www.yorkhospitals.nhs.uk/your-visit/patient-information-leaflets/
23. Peters SL, Yao CK, Philpott H, Yelland GW, Muir JG, Gibson PR. Randomised clinical trial: the efficacy of gut-directed hypnotherapy is similar to that of the low FODMAP diet for the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2016 Sept;44(5):447–59. doi: 10.1111/apt.13706
24. Saab O, Al-Obaidi H, Algodi M, Algodi A, Rashid Y, Al-Sagban A, et al. Yoga for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Official journal of the American College of Gastroenterology | ACG. 2022 May 12;10.14309/ajg.0000000000003524. doi: 10.14309/ajg.0000000000003524
25. Scenario: Management | Management | Irritable bowel syndrome | CKS | NICE [Internet]. [cited 2024 Aug 21]. Available from: https://cks.nice.org.uk/topics/irritable-bowel-syndrome/management/management/