Case Study 1: SIBO Improves Without Antibiotics, Antimicrobials or a Restrictive Diet

Patient Summary: 

• Overview Context: 
  • Sue has been on an 11 year digestive health journey, and has seen GI doctors multiple times for SIBO treatments. She has been treated with multiple rounds of herbal antimicrobials and rifaximin, with diminishing positive returns. She has been on a restrictive diet for 4 years and is underweight.
  • Sue is likely taking unnecessary medications and supplements. She said “whenever we started something, if it wasn’t working, we didn’t stop it, we just added more stuff.”

Visit 1 – Clinical Analysis:

Initial Impression: 50/100. 

Symptoms and Concerns

• Chief Complaints:
  • Bowel movement urgency
  • Diarrhea
  • Multiple bowel movements
  • Incomplete evacuation
  • Abdominal pain
• Onset/Timeline
  • 2010 July – Thyroid removed due to enlargement
  • 2011 January – Diarrhea/urgency/incontinence

Past Medical History

• Prior Diagnosis:
  • SIBO – 2014
  • Osteoporosis – 2022
• Medications:
  • Synthroid
  • Armour thyroid
    • Added by functional doc 
  • Low dose naltrexone
  • Rifaximin
  • Enteragam (Immunoglobulins)
• Supplements:
  • Vitamin K & D
  • Sunfiber (Guar gum) 
  • Calcium
  • Digestive enzymes
  • Mentha XL
  • Epicor
  • EPA/DHA “fish oil”
• Pertinent Labs:
  • SIBO Breath Test (12/2023)
    • H2 – 35.73 ppm
    • CH4 – 20 ppm
    • H2S – normal
• Blood Work (2022) 
  • TSH 0.362 (0.27-4.2)  
  • fT4 1.7 (0.9-1.7)
  • fT3 3.8 (2.3-4.1)

Prior Testing and Treatment History

• Previous Dietary Treatments:
  • Helpful
    • Gluten and dairy free  
    • Intermittent fasting  
  • No Response
    • Low FODMAP diet
• Previous Supplement Treatments
  • Helpful
    • Antibiotics (Rifaximin + Allinia) 
    • Antihistamines 
    • Elemental diet – helpful but had to stop due to excessive weight loss
  • No Response
    • Enteragam  
    • Low dose naltrexone
    • Armour
    • Mentha XL
    • Epicor (postbiotic) 
    • Guar gum 
    • Digestive enzymes
  • Negative Response 
    • Antimicrobials – increased GI distress

Initial Impression

• Clinical Commentary:
  • Too much focus has been placed on her positive SIBO breath test. The test has guided her provider’s decision to place her on multiple rounds of antibiotics, various supplements, and a low FODMAP diet, all without much improvement. She was experiencing psychological distress over the long-term dietary restriction and excessive medication/supplementation.

Visit 2 – Initial Recommendations:

• Initial Treatment Recommendations
  • Diet:
    • Stop low FODMAP diet 
    • Transition to ‘relaxed Paleo’ diet with protein focus to increase nutrient density and calories for weight gain. 
  • Lifestyle:
    • Increase yoga 5x/week
    • Walk daily
    • Weightlift 3x weekly
  • Supplements:
    • Start: 
      • Lactobacillus & Bifidobacterium probiotic blend, saccharomyces boulardii, and soil-based probiotics
      • GI support nutrients
      • Elemental diet shake to replace one meal daily or as a snack
    • Stop anything that isn’t helping, such as:
      • Sunfiber 
      • Digestive enzymes
      • Epicor
      • Mentha XL
  • Referral
    • Please ask your gastroenterologist to see if weaning off rifaximin, low dose naltrexone, and enteragam, would be appropriate for you.
  • Followup:
    • 5 weeks

• Pertinent Labs:
  • No labs were recommended. 
• Treatment Rationale
  • Most of the initial recommendations centered around simplifying and stopping what wasn’t helping. Understanding how a patient is responding to given therapies is important so they can avoid unnecessary treatments. Given the lack of benefit and unwanted weight loss from the low FODMAP diet, dietary expansion was indicated. 
  • We have also observed that when someone has taken multiple rounds of antimicrobials or antibiotics, they often benefit from more supportive therapies like probiotics and gut support nutrients. 
  • Unfortunately, she had never tried a therapeutic course of probiotics. We have found probiotics to be an effective therapy for those with SIBO. 
  • Lastly, we have found that although the research uses a 2 week exclusive elemental diet for SIBO, we don’t find this always necessary. I felt comfortable using the elemental diet as a daily meal replacement to improve her symptoms without concerns of additional weight loss.

Visit 3 – Follow-up Visit and Treatment Evaluation (5 weeks later)

• Subjective Assessment 
  • 60/100, 25% better
  • “I feel like I’m not taking a ton of pills anymore, which is much less stressful.”
• Current Symptoms:
  • Improved: 
    • Diarrhea
    • Urgency
    • Bowel movement frequency 
    • Stomach pain 
    • Incomplete evacuation
  • Worse: 
    • Reflux (newer symptom) 
• Response to Treatment 
  • Diet 
    • Helpful
      • Paleo Diet: Expansion from low FODMAP going well, no issues with food. Gained 3-4 pounds
  • Supplements
    • Helpful
      • Stopping medications
        • Rifaximin, low dose naltrexone and enteragam.  
      • Stopping supplements
        • Guar gum, digestive enzymes, epicor, mentha XL 
      • Probiotics
    • No change
      • Elemental diet 
    • Worse
      • GI support nutrients: Possibly irritated stomach, but not sure.
• Updated Treatment Recommendations
  • Note from Provider: 
    • “I’m very happy with your progress today! You’ve been able to get off many medications and supplements while seeing symptomatic improvement and weight gain. Please continue your current plan for another month and then reassess to see if you need to add in any of the new supplements recommended below. I would also trial GI support nutrients to see how you feel. If it doesn’t feel right to you, you can then take glutamine. If you’re still improving, simply continue the plan until we speak next. If symptoms plateau, add in the digestive enzyme supports.”
  • New Treatment:
    • Add in digestive enzymes with HCL if symptoms plateau. If no change, start betaine HCL. 
  • Continue: 
    • Lactobacillus & Bifidobacterium probiotic blend, saccharomyces boulardii and soil-based probiotics
    • Elemental diet shake to replace one meal daily or as a snack
    • Maintain dietary changes 
  • Followup: 8 weeks
• Treatment Rationale
  • After just 5 weeks of her plan, she saw a 25% improvement in symptoms. As this was a relatively short period of time, I wanted to see if her body would continue to improve on the current plan with some more time. However, if her improvements plateaued, I gave her a backup plan of stomach acid support. This is indicated because of her older age, history of osteoporosis, and SIBO diagnosis. 
  • Trialing GI support nutrients again was indicated because she wasn’t certain it caused a negative reaction.

Closing Thoughts

• This case study exemplifies 2 core principles we at the Ruscio Institute find important for optimal clinical outcomes. 
• #1) Understand the Response to Treatment
  • When Sue was working with her previous providers, she said “whenever we started something, if it wasn’t working, we didn’t stop it, we just added more stuff.” In her case, this led to following the low FODMAP diet for 4 years and taking supplements/medications that weren’t helping. By understanding whether or not certain therapies are helpful, this allows the individual to follow only the most impactful recommendations while discarding the rest. 
• #2) Treat the Person, Not the Labs
  • Sue’s previous providers focused more on her positive SIBO breath test, which led them to treating her with a restrictive diet, motility support (LDN), antibiotics, and avoiding probiotics. Focusing on labs can lead providers to miss the most important aspect of supporting an individual, which is whether or not their symptoms are improving. Of course, treating labs has its time and place, such as treating overt hypothyroidism, iron deficient anemia, or diabetes. However, when treating functional labs, this often leads providers astray, and instead one should focus on the individual’s symptoms. 
• Actions Items
  • #1) Make sure to ask your patients about their response to prior and current treatment recommendations. This will inform your current and future treatment plans. 
  • Understanding if a treatment was helpful or not helpful is critical for helping someone get better and avoiding unnecessary therapies. However, if someone says they tried something and it didn’t help, we need to further understand what they mean. Let’s use the example of probiotics. If your patient said they tried probiotics and they didn’t help, we can’t just take that at face value and move on. What kind of probiotic did they take? Was it from a reputable source? What dose did they take? How long did they take it for? These are the types of questions we have to ask to understand if someone gave probiotics a good therapeutic trial. 
  • #2) Use the patient’s symptoms, not their lab results, to guide your treatment plan.
    • Generally speaking, a patient’s symptoms will be the best guide for navigating whether a treatment plan is helping or not. If their symptoms are much better, but their SIBO breath test is still positive, focusing on the test result will lead to overtreatment, which we want to avoid.

Clinical Review: Does butyrate supplementation improve gut health?

Clinical Review Purpose

• There is a lot of talk about the health benefits of butyrate, however most of the evidence cited is mechanistic. We find what sounds good mechanistically doesn’t necessarily correlate with positive clinical outcome data. While butyrate is important for the health of our colon, does this mean we should supplement with it for improving digestive health? We reviewed the literature to help answer this question.

Overview of Butyrate 

• Butyrate is a short-chain fatty acid created from fermentable carbohydrates by our colonic gut microbiota. The majority of butyrate is then absorbed into the colon cells, where it is used for energy in order to strengthen the intestine epithelial barrier, reduce inflammation, and maintain immune homeostasis [1].
• Various gastrointestinal conditions have been associated with lower levels of fecal butyrate, including IBS and IBD [2, 3]. However, we have to be careful not to conflate what observational data reports with what we would expect from outcome studies. As an example, a 2022 clinical trial found even though IBS patients have lower levels of fecal butyrate, a low FODMAP diet improved IBS symptoms in 67%, despite further decreasing butyrate levels. This is just one example of why we focus more on outcome data versus mechanistic data.
• While it seems clear butyrate is an important short chain fatty acid for the health of our colon, what does the outcome data suggest for butyrate and various gastrointestinal disorders?

Butyrate & IBS 

• High-Level Overview
  • According to the most recent clinical trials, butyrate appears to have a beneficial impact on IBS symptoms. However, the largest study performed on butyrate and IBS did not have a placebo group, so we can’t draw firm conclusions based on this data.
• Supporting Research
  • A 2022 study of 2,990 IBS patients were all treated with 300 mg butyrate. After 3 months, patients saw improvements in abdominal pain, gas, diarrhea, constipation, urgency, nausea, and quality of life, with 94% of participants stating they would continue using butyrate after the study. This study lacked a placebo group, so it is hard to discern the true magnitude of benefit from butyrate because IBS patients tend to have a higher placebo response rate.
  • In a 2013 study, 66 IBS patients were randomized to take either placebo or 300 mg of butyrate. The butyrate group saw greater improvement in IBS symptoms, with 53% reporting subjective symptomatic IBS relief, compared to just 16% in the placebo group.

Butyrate & IBD

• High-Level Overview
  • The benefits of butyrate for IBD are unclear. However, there is a trend for higher doses of 1.5 to 4 grams/day being more clinically useful for those with IBD.
• Supporting Research 
  • A 2021 systematic review of 8 RCTs on ulcerative colitis patients treated with butyrate enemas concluded “The current evidence is limited and does not support the application of butyrate enemas in UC.”
  • A 2022 RCT on IBD pediatric patients found 300 mg of butyrate had no impact on symptoms or calprotectin. 
  • However, a 2020 observational study of IBD patients already in remission found 1 gram of butyrate, in addition to mesalamine, led to greater long-term remission rates compared to mesalamine alone. 
  • Finally, a small 2000 study of 13 Crohn’s patients found 4 grams of butyrate per day led to clinical remission in 53% after 2 months.

Butyrate & Traveler’s Diarrhea

• High-Level Overview
  • Butyrate supplementation may be effective for preventing traveler’s diarrhea, according to one placebo-controlled trial.
• Supporting Research
  • In a 2014 study, 42 participants who traveled to another country were randomized to take either placebo or 1.5 grams of butyrate. Compared to placebo, the butyrate group experienced significantly reduced incidence of traveler’s diarrhea (4.5% butyrate vs 40% placebo).

Butyrate & Diverticulitis

• High-Level Overview
  • Butyrate supplementation may be helpful for preventing acute diverticulitis in those who are at risk.
• Supporting Research 
  • In a 2014 study, 52 participants with diverticulosis were treated with placebo or 300 mg of butyrate. After 1 year, those taking butyrate had a lower incidence of acute diverticulitis flare (6.7% vs 31.8%). The butyrate group also experienced greater diverticulosis symptomatic relief compared to the placebo group (56.7% vs 22.7%).

Using Butyrate in Clinical Practice

• Dose: 300 mg to 4 g/day. 
• Safety: All dose ranges were well tolerated in all studies. 
• Cost: $30.99 for 100 capsules (600 mg/capsule) 
• Sequencing: Trial butyrate alongside GI support therapies, such as probiotics and GI supportive nutrients. Example hierarchy:  
  • 1) Dietary modifications (relaxed Paleo, low FODMAP, etc)
  • 2) Probiotics (lacto/bifido, saccharomyces boulardii, soil-based)
  • 3) Gut supportive nutrients (glutamine, aloe, slippery elm, zinc carnosine, etc)
  • 4) Butyrate
  • 5) Herbal antimicrobials

How This Changes Clinical Practice

Clinical Takeaways

• Although there are a limited number of clinical trials, butyrate supplementation does appear to be beneficial for a variety of gastrointestinal conditions, including IBS, IBD, diverticulitis prevention, and traveler’s diarrhea. While better studies are needed, the overall trend in the data suggests recommending a trial of butyrate to your patients is worthwhile, as long as they already have the foundational GI recommendations already in place (appropriate diet, probiotics, GI supportive nutrients).   

Final Comments

• We are currently experimenting with butyrate early on in our treatment hierarchy, especially for individuals with more functional gastrointestinal symptoms. We are recommending 1.2-3.6 grams per day. With each individual we follow up with, we are tracking their response to butyrate to identify if we should be recommending butyrate to more individuals.