2018 Integrative SIBO Conference Highlights

Thanks to presenters Allison Siebecker, ND, MSOM, LAc; Satish Rao, MD, PHD, FRCP (LON), FACG, AGAF; Jennifer Krieger, ND; Lisa Hanson, PhD, CNM, FACNM; Nirala Jacobi, ND; and Lisa Shaver, ND, LAc, for taking the time to write about their colleagues' presentations.

In April, the 2018 Integrative SIBO Conference was held at Le Meridien New Orleans Hotel. The 2-day event showcased expert presentations on a variety of topics related to small intestine bacterial overgrowth (SIBO). The presentations and panel discussions covered subjects including pediatrics, small intestine fungal overgrowth (SIFO), colonic microbial migration, opioid and traumatic brain injury–induced gut motility disorders, dentistry, obstetrics and gynecology, methane, opioid addiction and SIBO related eating disorders.

Some of the conference presenters provided summaries of their colleagues’ presentations. We thank them for taking the time to summarize these sessions for the benefit of Natural Medicine Journal readers.

For more information about this year’s conference—or to learn about the details of the 2019 conference—visit the conference website.

Microbiota and the Jejunum: Relationship to Bacterial Overgrowth and Breath Tests

Presenter: Richard McCallum, MD, FACP, FRACP (AUST), FACG, AGAF

Reviewer: Allison Siebecker, ND, MSOM, LAc

Introduction

• Normally, the amount of bacteria in the gastrointestinal tract is minimal until the distal ileum and colon, which have trillions of bacteria.
• In SIBO the number of bacteria is 100-10,000 times greater than normal: 10³ colony-forming units (CFUs) in the duodenum and ≥10⁵ CFUs in the jejunum, which leads to GI symptoms.
• Culture testing procedure: endoscope is placed into duodenum or jejunum, juice is aspirated and cultured.
• Difficulties of culture testing: only detects ~20% of bacteria; quantification may take 2 days or more; endoscopy is an invasive procedure requiring sedation and loss of a day’s work; distal small intestine is not usually tested.
• Breath testing: measures exhaled gases only produced by bacteria (hydrogen) and methanogens (methane-present in about 30% of populations) in the intestine. Breath testing is an easier alternative to culture testing.
• Glucose breath test (GBT)
  • Glucose is mainly absorbed in the jejunum but some can reach ileum and colon
  • Measures jejunal bacterial overgrowth (not ileal)
  • Procedure: patient drinks 75-100 g glucose in 100 mL water after a day of preparation, then breath is sampled every 15 minutes up to 3 hours
  • Positive GBT: hydrogen >20 ppm rise and/or methane 10 ppm rise over baseline in 3 hours. Hydrogen usually rises within 90 minutes with jejunal bacterial overgrowth on GBT.

Research Report

Dr McCallum discussed his 2 recent SIBO studies which used culture, glucose breath, and DNA testing on 18 patients with GI symptoms.

• The human jejunum has an endogenous microbiota that differs from those in the oral cavity and colon.
• Does a glucose-based hydrogen and methane breath test detect bacterial overgrowth in the jejunum?
• Focus:
  • Identify which bacteria are present in patients with jejunal SIBO compared to those with GI symptoms but no jejunal SIBO
  • Compare culture results with GBT results for the diagnosis of SIBO
• Methods:
  • Total amount of bacteria in the jejunum was evaluated with culture, GBT, and DNA. Genus and species was reported from culture and DNA.
  • A new culture sample method was used to obtain a better representation of microbial population: sterile water was injected through endoscope before gentle aspiration.
• Results:
  • GBT results do not correlate well with culture CFU or DNA results.
  • Hydrogen and combined hydrogen and methane gases correlated significantly with non-CFU (dead or nonviable) bacteria, suggesting GBT detects some type of bacterial dysbiosis in the jejunum (abnormal bacterial growth or death).
  • SIBO/jejunal dysbiosis may cause glucose malabsorption, allowing glucose to move into the distal ileum and colon, and represent methanogen fermentation occurring there during a GBT (especially when gases continue to be elevated after 90 min).
• DNA results:
  • Patient jejunal DNA was compared to limited available normal oral, stomach, jejunal, and colon DNA (future goal is to collect more normal samples).
    • Oral and jejunal bacteria were similar to each other, but very different than colonic bacteria in both patients and normal samples.
    • The jejunum has a distinct microbial profile that differs from oral and colonic flora.
    • Bacterial overgrowth was not correlated with a change in phylum distribution (ie, firmicutes, bacteroidetes, fusobacteria, actinobacteria, proteobacteria) compared to normal.
    • Colonic bacteria was not present in any of the 18 patients, including those with jejunal SIBO, suggesting that the large bacterial increase found in SIBO is not due to colonic back migration. This was noted as a key conclusion since it contradicts the common definition of SIBO as an overgrowth of colonic bacteria due to back migration.

Conclusion: Functional (non-ulcer) dyspepsia may be jejunal dysbiosis (microbial antigens, metabolites, toxins).

Commentary

• In this research, only the 10 patients with a culture value of ≥10⁵ CFUs were considered to have SIBO, but all 18 patients met the diagnosis of SIBO by the value of >10³ CFUs.
  • According to the North American Breath Test Consensus: “Historically, a bacterial concentration of 10⁵ CFU/mL has been used for identification of…SIBO. However, this cut-off is not well-validated and has been a point of controversy… Currently a bacterial concentration of >10³ CFU/mL is generally considered significant.”
  • Dr McCallum commented that ≥10⁵ CFUs is the most defensible when publishing data, which is why this value was used.
  • Recent studies using culture testing often report findings for both >10³ and ≥10⁵ CFUs in their results. Analysis for >10³ was not reported for these studies and could have affected interpretation, especially since there would no longer be a non-SIBO group of patients.
• Some of the bacteria classified here as exclusively jejunal were classified as colonic bacteria in the presentation that followed (“SIBO: What’s Bugging Your Patients”), including Klebsiella, Citrobacter, and Enterobacter. There appears to be some disagreement about which bacteria represent different organs.

The Gut is the Roots of the Tree: How Dysbiosis and Candida Overgrowth Are Often the Underlying Cause of Your Patients’ Chronic Complaints

Presenter: Margaret Beeson, ND

Reviewer: Satish Rao, MD, PHD, FRCP (LON), FACG, AGAF

Session Overview: Dr Beeson presents an excellent overview of the state of the art, how commensal organisms make up our microbiome, and how Candida colonization can become pathogenic. She makes a good case for the consideration of Candida overgrowth or small intestinal fungal overgrowth (SIFO) as a coinfection or superinfection of SIBO. Her talk included a nice overview of the pathogenic mechanisms, how this commensal can become pathogenic, and what remedies one can take including dietary, natural, and prescription therapies to combat this growing health problem.

The microbiome

• The microbiome is composed of the different microbes (bacteria, bacteriophage, fungi, protozoa, and viruses) that live on and inside the human body
• Genes in our microbiome outnumber our own genes by about 100 to 1
• Most bacteria are beneficial colonizers
• These microbes perform many “housekeeping” functions to maintain cell function and other properties to sustain the body site ecosystem
• Our gut microbiome is influenced by various factors including mode of delivery (vaginal or cesarean birth), breastfeeding or formula feeding, medications, diet, and physical activity

Yeast colonization

• Yeasts are normal flora in feces and in vaginal secretions, but almost absent or very few in the small bowel
• Alteration in host cellular defenses, physiology, or normal flora associated with Candida colonization can convert it from commensal to pathogen
• Disease represents an opportunistic infection
• Candida species are the most virulent yeasts
• Yeasts play a role in the pathogenesis of chronic infections, dermatoses, hormonal problems, and inflammatory disorders

Pathophysiology

• Candidiasis is an underdiagnosed and undertreated cause of dysbiosis
• Manifestations are protean: cutaneous, mucocutaneous, subcutaneous, or systemic
• Candida albicans infection leads to barrier breakdown and a mitogen-activated protein kinase (MAPK)/nuclear factor (NF)-κB –mediated stress response in the intestinal epithelial cell line C2BBe1
• Modes of colonization and infection:
  • Adhesion/attachment, including electrostatic forces
  • Induced endocytosis
  • Active penetration through secretion of factors
• Pathogenesis:
  • Contributes to leaky gut—mycelial form imbeds hyphae in mucosa
  • Biofilms—early acquisition of drug resistance
  • Inflammatory response—interferon (IFN)
  • Resistance mechanisms—actively blocks nitric oxide (NO) production by macrophages via secreted mediator
  • Induction of epithelial cell apoptosis and inactivation of anti-apoptotic proteins
  • Pheromones stimulate biofilm formation and sexual reproduction
• Co-infection
  • C albicans can increase the virulence of bacterial pathogens such as E faecalis, Staphylococcus aureus, and Serratia marcescens
  • More severe disease than infection with the bacterial species alone

Risk factors for fungal disease

• History of antibiotic use, even remote history
• Diet high in sugar
• History of yeast infections

Treatment of Candida-related illnesses

• Probiotics: Lactobacillus acidophilus, Saccharomyces boulardii
• Anti-Candida diet: avoiding white sugar/white flour
• Nystatin
  • Topical and oral antifungal agent, generally not absorbed
  • Used largely to treat skin and oropharyngeal candidiasis
  • Active against many species of yeast including Candida albicans
  • Not active against bacteria, protozoa, or viruses
• Adherence to treatment depends on the patient-provider relationship and support
• Need time to reevaluate the symptoms in visits—not just “I am no better” then on to another treatment regimen
• Record specifics of symptoms and revisit with each encounter

Direction of future naturopathic treatments

• Acteoside from Colebrookea oppositifolia
• Essential oil from Cinnamomum cassia
• Essential oil from Thymus vulgaris
• Quercetin and isoquercetin
• Aliginate oligosaccharide (OligoG) derived from seaweed
• Colistin (antibiotic) with echinocandin (antifungals)

Conclusions

• Dysbiosis can be the underlying cause of many gastrointestinal complaints
• Candida albicans colonization in the digestive tract is a significant manifestation of dysbiosis
• Opportunistic features can lead to pathogenicity
• Treating Candida infections appropriately can result in long-term resolution of many chronic complaints
• Fungal overgrowth is an important consideration alongside treating SIBO

From Mouth to Gut: How Everything You Swallow—Including Dental Toxins—Affects Your Intestines

Presenter: Blanche D Grube, DMD, IMD
Reviewer: Jennifer Krieger, ND

Session Overview: This presentation targeted oral health, the connection between treated teeth (including mercury amalgams, root canals, titanium implants, and crowns) and the digestive tract, and the correlation between the microflora found in the dental root system and its correlation to SIBO.

Session recap:

• Dangers of mercury in dental amalgams:
  • There is no safe or harmless level of mercury
  • In 1991, the WHO confirmed that the mercury contained in dental amalgams is the greatest source of mercury vapor in nonindustrialized settings, exposing the patients with these amalgams to mercury levels significantly exceeding those set for food and for air
  • There is a correlation between the total amalgam surfaces in a mouth and organic mercury found in saliva, suggesting both methylating and nonmethylating bacteria can enhance the formation of toxic methylmercury
  • Bacteria that activate methylmercury increase mercury uptake and thus increase the worry for mercury toxicity
  • The mercury vapor that comes from gasses from dental amalgams as a byproduct of bacteria that activate the methylmercury can cross the blood brain barrier, pass through the nasal sinus directly to the brain stem, attack the optic nerve, cause birth defects, and damage red and white blood cells
  • Studies have demonstrated a statistically significant increase in the incidence of mercury-resistant bacteria following installation of amalgam fillings and for a short period of time following their replacement with glass ionomer fillings. These peaks in incidence of mercury-resistant bacteria correlated with peaks of mercury elimination (as high as 1 mM in the feces) immediately following amalgam placement and immediately after replacement of the amalgam fillings
• Mercury and the GI system:
  • The effects of mercury on the GI system typically present as abdominal pain, indigestion, inflammatory bowel disease, ulcers, and bloody diarrhea
  • Mercury ingestion has also been associated with the destruction of intestinal flora which can increase the amount of undigested food products in the bloodstream, causing immune-mediated reactions and reduced resistance to pathogenic infection
  • Mercury must be demethylated and converted to elemental mercury in order to be excreted through the feces
  • In animal studies, when subjects were given antibiotics in combination with mercury, the subjects had more mercury stores in their kidney, brain, lungs, blood, and skeletal muscle and excreted less mercury in their feces than controls
• Root canal–treated teeth:
  • Human endodontic and periodontal infections are associated with a complex microflora in which more than 500 microbial species have been documented
  • DNA testing of root canal–treated teeth (as well as oral blood, cavitations, implants, and extracted teeth) using polymerase chain reaction (PCR) has detected highly specific genes in a variety of pathogens
  • Of the 88 different microbial pathogens that have been detected in the oral samples, 39 pathogens have been connected to SIBO and other GI symptoms such as Crohn’s Disease.

Conclusion: Dr Grube reaffirmed the harm and disease that is associated with mercury amalgams and why they should be removed, and he explained the connection between the oral microflora and the potential for mercury toxicity. This presentation also brought attention to the vast microbiome of the mouth, which can be tested via DNA PCR and has been correlated to various health conditions that are not directly associated with the oral cavity, such as SIBO.

Chronic Pelvic Pain and IBS

Presenter: Danielle Lewis, ND

Reviewer: Lisa Hanson, PhD, CNM, FACNM

Session Overview: The speaker discussed the relationship between chronic pelvic pain and IBS. The presentation included the scope of the problem of pelvic pain and strategies for diagnosis and management.

Session Recap: Dr Lewis discussed the scope of the problem of chronic pelvic pain (CPP).

• A widespread problem—affects 33% of women and 15% of men.
• Leads to significant suffering, poorer quality of life, increased healthcare visits, and surgeries such as hysterectomy
• 35% of women with CPP have IBS
• 85% of people with IBS have SIBO

Dr Lewis reviewed the evidence that IBS/SIBO may be the underlying pathology of CPP

• Diagnosis can be complex and difficult
• Patients with IBS present with pelvic organ prolapse, constipation, urinary symptoms, and decreased sexual enjoyment.
• The urinary tract has a unique microbiome. The antibiotics used to treat inflammatory illness related to CPP may disrupt the delicate microbial environment and lead to a vicious cycle.
• IBS may lead to hypersensitivity algesia and visceral hypersensitivity.

The connection between IBS/SIBO and interstitial cystitis, endometriosis, chronic prostatitis, and other CPP-relevant conditions were discussed.

• The NIH has described the connections between IBS and a number of conditions relevant to CPP.
• Interstitial cystitis (IC) affects 25% of women with pelvic pain.
• In one study women with IC and IBS had a positive hydrogen breath test.
• It is important to rule out other pelvic or gut pathology in IC patients.
• Patients with chronic prostatitis (CP) should be evaluated for IBS and other underlying pathology.
  • Patients with CP often receive antibiotics, but antibiotics are not indicated unless a bacterial cause is identified.
• Endometriosis affects 1 in 10 women. Women with endometriosis are 2.5 times more likely to have IBS, and symptoms can overlap between these entities. Therefore pain is increased when both are present.
• Treatment implications were presented in a series of research findings outcomes including antibiotics, probiotics, and dietary changes (including FODMAP and low-histamine diet).

Dr Lewis presented a clinical case that highlighted the link between IB and CPP. The patient’s case was complicated by multiple courses of antibiotics and a surgery. A trial of SIBO treatment was used with a biphasic diet. The patient improved with a reduction of high-histamine foods. Pelvic floor assessment revealed a very tight pelvic floor. Acupuncture improved visceral sensitivity. Counseling was an important component of treatment. Prokinetics and pelvic floor rehab were important for improvement and maintenance.

Conclusion: The connection between IBS/SIBO and CPP are important for female and male clients. Management includes comprehensive assessment, judicious use of laboratory confirmation, and holistic treatment with a variety of strategies to address and manage pain and improve quality of life.

Small Intestine Bacterial Overgrowth in Children from Low-income Countries

Presenter: Jeffrey Donowitz, MD

Reviewer: Nirala Jacobi, ND

Session overview: Due to poor sanitation and fecal contamination of the domestic environment, children in low-income countries are at risk of environmental enteric dysfunction (EED), which can lead to stunted growth and death. This presentation reviewed the preliminary data of a research study exploring the possibility of SIBO contributing to EED and stunting in children in low-income countries.

Session recap:

EED in low income countries leads to:

• Increased childhood morbidity and mortality
• Reduced cognitive development
• Reduced adult economic productivity

EED often is caused by repeated and persistent infections.

SIBO has been reported in high rates in asymptomatic children in the developing world.

This study asked the following questions:

• Is SIBO associated with EED?
• Why would children in lower middle income countries (LMICs) develop SIBO?
• Is SIBO associated with growth failure and malnutrition?
• What bacteria overgrow in SIBO?

The first look: a cross-sectional study of SIBO in Bangladeshi 2-year-olds

• 90 children tested with a GBT
• SIBO prevalence was 16%
• SIBO was predicted by poor sanitation but not diarrheal illness
• SIBO at 2 years of age was associated with increased stunting

Cross-sectional stool microbiome analysis of Bangladeshi 2-year-olds

• There was no significant difference in genus level alpha or beta diversity between SIBO positive and negative children. Alpha diversity represents the degree of diversity within a given sample, and beta diversity represents the similarity of a sample to the rest of the group (ie, those with the same SIBO status)
• The presence of SIBO was associated with increased fecal Lactobacillus

The next questions the research team are focused on:

• Can SIBO predict stunting in a longitudinal study?
• Is SIBO associated with neurodevelopmental delay?
• Is the 16s signature of SIBO consistent across all age categories?
• Does SIBO alter the metabolome in stool or serum?

Conclusion:

• SIBO (as diagnosed by glucose-hydrogen breath testing) is prevalent in children from low-income countries.
• SIBO is associated with markers of intestinal inflammation and endothelial damage.
• SIBO is associated with poor sanitation but not preceding diarrheal disease.
• SIBO is associated with an increase in fecal Lactobacillus spp. but not changes in diversity.

Probiotic Bacteria and Women’s Health

Presenter: Lisa Hanson, PhD, CNM, FACNM

Reviewer: Lisa Shaver, ND, LAc

Session overview: Overview of the female microbiome and review of literature of probiotic interventions in pregnancy and bacterial vaginosis (BV).

Session recap:

• Pilot study shows group B Strep (GBS) decreased with topical Lactobacillus, likely due to change in pH. Women with more Lactobacillus organisms have fewer GBS bacteria.
• Some strains of vaginal probiotics produce lactic acid, which disrupts pathogenic biofilm and creates thick healthy biofilm
• Vaginal microbiome increases in Lactobacillus in pregnancy and placenta microbiota seeds the baby, then baby is exposed to microbes during birth, hence cesarean section is a problem for development and immunity. Breastfeeding and skin contact contribute to a healthy immune system.
• Findings of literature review (various quality of studies):
  • In pregnancy, probiotics or probiotic foods reduce preterm labor, BV and other vaginal pathogens, systemic infection, risk of pre-eclampsia, gestational diabetes, BG, insulin, GI symptoms, and high sensitivity C-reactive protein (hs-CRP).
  • In pregnancy, probiotics or probiotic foods increase insulin sensitivity, IFN-γ, and diversity of baby’s microbiota.
  • In pregnancy, probiotics do not reduce risk of cesarean section, alter maternal weight gain, alter Apgar score, increase BP, or increase adverse events.
  • In BV, oral or vaginal probiotics significantly increase BV cure, increase time to BV recurrence, decrease vaginal pH, and decrease Nugent score.

Conclusion: Probiotics may be safely used in pregnancy. Lactobacillus may be used for treating and preventing BV. There are no serious adverse events using probiotics for BV. Always separate probiotics and antibiotics. One probiotic’s benefit cannot be attributed to another probiotic. More controlled trials are needed to strengthen clinical practice recommendations.

Editor's note: For more information on SIBO, look for our special report, "Small Intestinal Bacterial Overgrowth: A clinician's guide to evaluation and treatment" in our Research Guide Library.