A 69-year-old female presents with nausea and vomiting, abdominal pain, heart palpitations.  She describes herself as high strung and anxious.  Even the gut pain gives her anxiety leading her to worry about underlying cancers and other possible health issues.  When gut pain increases anxiety gets worse and anxiety remits as gut symptoms improve.  It is obvious the gut/brain axis is heavily involved in this case. It is discussed with the patient how the gut has more nerve endings than any other organ in the system and this is likely to be a key reason for the anxiety.  As we know, only 20-30% of the signal along the vagal nerve which connects brain to gut, comes from the brain.  Most of the signal is input coming from the gut.  This is part of a major channel of the gut-brain axis.  

The patient is on a PPI, which gives symptomatic relief, but can create certain long-term side effects.  Some potential side effects noted in the literature include decreased absorption of nutrients, increased risk of food sensitivities and allergies secondary to not fully degrading protein structures, and atrophy of the lining as PPIs increase ADMA that blocks local production of nitric oxide, decreasing blood flow. 

While it is generally agreed upon in the functional medicine space that dysbiosis as well as food irritants can play a role in gut-based symptoms that affect the CNS, it is not always clear which one should be addressed first, or if they should always be addressed together.  As is the case with all patient care, there is not one singular answer, but we will always be led by the patient’s history.  A good rule of thumb is that if we want to drive the fastest resolution to gut based irritation, we will work both on diet and dysbiosis at the same time.  Dietary interventions may be based around certain anti-inflammatory diets and/or food sensitivity testing.  Consider doing stool and food sensitivity testing together when we need to identify the most likely culprits of gut-based irritation and resolve inflammation most quickly.  Otherwise, working with a stool test first, implementing a lower inflammatory diet which emphasizes whole foods, decreasing sugar as that feeds a compromised microbiome, and removing other highly inflammatory foods such as gluten and dairy and then deciding if food sensitivity testing is needed is often the more clinically relevant approach.  

Stool testing was done, with evidence of dysbiosis including staph and strep which can both cause nausea and abdominal pain.  There was a virulent strain of H. pylori which can contribute to reflux. Even though H. pylori releases urease, which neutralizes HCL to help it survive, the parietal cells can begin to overproduce HCL to compete.  Eradication of H. pylori will support minimizing reflux.  Also, foods that increase IgG antibodies also increase reflux.  Additionally, IgG antibodies can in and of themselves increase permeability.  This is an example of how eradicating the pathogen as well as removing foods one is sensitive to will speed up outcomes.  In addition to H. pylori, patient stool testing shows Candida which will contribute to bloating and therefore reflux as well as low elastase production indicating poor pancreatic dysfunction.  

Low digestive enzymes will allow dysbiotic bacteria to form more biofilm making it more pathogenic.  This is why therapies directed at increasing bile solubility should not only be thought of for liver detoxification, cholesterol lowering but also to prevent and treat dysbiotic flora.  The patient also noted a history of gallbladder spasms and discomfort with fattier meals.  While there are many connections between the gut-brain axis, another is the connection of bile acids and the hypothalamic axis.  Dysregulation of bile acids directly affects the HPA axis and when the levels are abnormal, they cause disruption in cortisol.  They first cause a heightened cortisol response, and then overtime cause adrenal burnout, creating fatigue.  This is exactly the pattern that was observed in this patient.  Their cortisol was spiking throughout the day, resulting in an am cortisol that was too high, crashing at noon resulting in afternoon fatigue the patient noted, and then spiking at night interfering with sleep.  She responded well to GABAinergic therapies that competed with cortisol, such as GABA in the pm to help her sleep.  We now recognize that gallbladder issues may be contributing both to her dysbiosis as well as her dysregulated cortisol.  

The patient used DGL or deglycerized licorice to help wean off her PPI.  This strategy protects the tissue but also increases the strength of the lower esophageal sphincter (LES) if done in a chewable or powder.  This is because if it interacts with taste buds, it sends a signal to the LES to constrict, preventing reflux.  DGL also has research that shows eradication of H. pylori.  This was combined with sulforaphane from broccoli sprout which increases anti-bacterial peptides that kill H. pylori.  This also decreases risk of gastric cancers which helps to sooth the nerves of the patient while improving dysbiosis.  Sulforaphane also crosses the blood-brain barrier and has been shown to help with depression and anxiety.  Caprylic acid was used to address yeast.  

The patient notes discomfort with some of the gut-based treatments.  Die-off was discussed which is common, as LPS sheds from biofilm making people feel worse.  She was anxious to see improvement so she wished to push through and do interventions that would speed up the process.  At this point we measured foods she was sensitive to with the understanding that if she were to continue to eat foods that produce IgG, this would continue to make her gut permeable and keep her from healing.  Food removal was added to the protocol.   This reduced irritation allowed her to more easily tolerate her anti-microbials and the rebuilding of the gut microbiome.  

While an abnormal cortisol response is usually treated with adaptogens and nutrients such as B5, B6 and vitamin C, in this case, treatment of gallbladder disorders will help with cortisol regulation.  The patient began lipotropic factors including choline, MSM, taurine, and dandelion to increase solubility of the bile.  This is a key part of addressing her gut-brain axis in addition to addressing dysbiosis and food sensitivities that are also a part of her complete picture.  Also, the PPI that she was weaned off creates atrophy to the gut lining.  Use of nitric oxide therapies such as beet and spinach to repair atrophy secondary to the PPI will be helpful.  Interesting, the increased production of nitric oxide will also decrease adherence of bacteria, helping with underlying dysbiosis and gut lining repair in a multitude of ways. 

Petrescu AD, Kain J, Liere V, Heavener T, DeMorrow S. Hypothalamus-Pituitary-Adrenal Dysfunction in Cholestatic Liver Disease. Front Endocrinol (Lausanne). 2018 Nov 12;9:660. doi: 10.3389/fendo.2018.00660. PMID: 30483216; PMCID: PMC6240761.