Dr. Mark Pimentel is a professor of medicine and gastroenterology at Geffen School of Medicine UCLA and associate professor of medicine at Cedars-Sinai Medical Center, Los Angeles. He is also the executive director of the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai, https://csmast.com. A pioneering expert in irritable bowel syndrome (IBS), Dr. Pimentel’s research led to the first-ever blood tests for IBS, https://ibssmart.com. Dr. Pimentel has served as a principal investigator for numerous clinical investigations of IBS and the relationship between gut flora composition and human disease. Dr. Pimentel is a diplomate of the American Board of Internal Medicine, a fellow of the Royal College of Physicians and Surgeons of Canada, and a member of the American Gastroenterological Association, the American College of Gastroenterology, and the American Neurogastroenterology and Motility Society.

Pam Emmer is a GI motility patient who has overcome SIBO, small intestinal bacterial overgrowth. She has been a patient advocate, fundraiser and cheerleader for Cedar Sinai Medical Center in LA and the Mast Program for almost 10 years.

Pam and I met with Dr. Pimentel at DDW 2023 in Chicago where we spoke about intestinal methane overgrowth, how to use prokinetics, motility and pooping – what’s the difference, biomarkers for malabsorption and its relationship to SIBO and upcoming clinical trials for the MAST program.

 ClICK HERE TO LISTEN:

Also, listen wherever you hear podcasts. Its called

” IBS Chat ” Episode 13

Find Pam Emmer at:

Find Jeffrey Roberts and IBS Patient Support Group at:

 

From Dr. Pimentel’s team:

ARCHAEA HAVE DIFFERENTIAL EFFECTS ON SYMPTOMS AND THE MICROBIOME THAT DEPEND ON METHANOGENIC COMPOSITION AND GI TRACT LOCATION

  • There are two prevalent methanogens in the GI tract, Methanobrevibacter and Methanomassiliicoccus, which compete with each other.
  • Methanogen syntrophs (bacteria that make hydrogen for the methanogens), were different in the large intestine vs. the small intestine. In stool, methanogens correlated with syntrophs Christensenellaceae and Ruminococcaceae. Whereas in the duodenum, methanogens correlated with Actinomycetaceae, Neisseriaceae and Prevotellaceae.
  • Symptomatically, in the large intestine methanogens correlate with constipation, straining, bloating, incomplete evacuation and less diarrhea. whereas in the small intestine, methanogens correlate with less diarrhea only.
  • Identified Lactobacillaceae as a small intestine disrupter!!
    But conversely, another DDW study (below) found that Lactobaccilus reuteri protects against small intestinal injury. And many studies (and patients) show benefit from lactobaccilus probiotics, so we’ll have to see how and if, this new and different research fits in to what is already known.

THE FIRST LUMINAL SHOTGUN SEQUENCING OF THE SMALL INTESTINE IDENTIFIES SPECIFIC STRAINS OF ESCHERICHIA AND KLEBSIELLA IN SIBO WHICH ARE LINKED TO GASTROINTESTINAL SYMPTOM SEVERITY.

  • Dr. Pimentel and team had previously identified E. Coli and Klebsiella to be the main overgrown culprits in hydrogen SIBO. This study has now identified the overgrown Klebsiella species as K. pneumoniae and K. aerogenes.
  • Escherichia and Klebsiella accounted for 40.24% of all small intestine microbes in SIBO subjects, vs. 5.6% in non-SIBO. The small intestine microbiome diversity was significantly decreased with this change.
  • K. aerogenes correlated with severity of abdominal pain, diarrhea and excess gas. E. coli correlated with severity of abdominal pain and diarrhea.

INCREASED COLIFORMS IN THE SMALL BOWEL ARE A SIGNATURE OF PATIENTS WITH SIBO AND PROFOUNDLY IMPACT THE LUMINAL RESIDENT MICROBIAL COMMUNITY

  • Validated the cut-off for SIBO culture testing as ≥103 CFU/mL using MacConkey agar only and not blood agar, a method still being used in some SIBO culture studies (and which may account for troubles lining up breath testing with culture testing).
  • The team had previously identified sampling techniques needed for an accurate sample –
    On Twitter, Dr. Pimentel said: “Super important from Reimagine study to assess small bowel microbiome. You must use a protected catheter. You must get both free fluid and mucus (viscous). You must break the mucus before sequencing. Years of work to get this validated.”

TRANSCRIPTOMICS IN SIBO PATIENTS REVEALS THE IMPORTANCE OF KLEBSIELLA IN DYSREGULATION OF GENE EXPRESSION ASSOCIATED WITH GUT IMMUNITY AND MOTILITY

  • Genes are affected in hydrogen SIBO and are dependent on Escherichiaand/or Klebsiella colonization.
  • The down regulated genes are involved in protection against cellular stress, immune response to Gram-negative bacteria, and control of gut barrier function.
  • The up regulated genes are associated with pro-inflammatory response, inhibition of gut motility, histamine secretion, protein digestion, and impairment of wound healing.
  • Klebsiella induced host immune responses even at sub-SIBO levels (below 10CFU/mL)!

DYSBIOSIS INDUCED BY CDTB TOXIN PROMOTES CHANGES IN MICRORNA EXPRESSION THAT MODULATE EXPRESSION OF GENES ASSOCIATED WITH GUT MOTILITY, BARRIER FUNCTION AND PAIN

  • Food poisoning via CdtB toxin creates 3 dysbiotic gut microtypes (microbiome types): normal-like, E. coli (hydrogen SIBO) and Desulfovibrio (hydrogen sulfide SIBO), which alter miRNA and gene expression, dysregulating circadian rhythm. The greatest gene expression or miRNA changes were seen in the E. coli group with impaired gut barrier function, motility and enhanced visceral hypersensitivity (pain).

  • Dr. Pimentel said on Twitter: “This toxin from food poisoning lead to SIBO in animals that is almost exactly what we see in humans. Hydrogen producers go up. Hydrogen sulfide producers go up. And the host markers link to visceral hypealgesia [pain], barrier dysfunction [leaky gut], motility. Huge validation for the role of CdtB and vinculin.”

BREATH TEST RESULTS IN IBS-D SUBJECTS ARE ASSOCIATED WITH DIFFERING BOWEL MOVEMENT MORPHOLOGY DETECTED BY ARTIFICIAL INTELLIGENCE

  • Hydrogen sulfide positive level may be changing to ≥ 2ppm. “H2S produces a graded diarrhea effect with effects beginning at ≥2ppm and increasing with higher levels. …as H2S levels increased, the stool volume becomes increasingly irregular, particularly above a threshold ≥2ppm.”

INCREASED FUNGAL LOADS DETECTED IN DUODENAL ASPIRATES USING MULTIPLEXED DIGITAL POLYMERASE CHAIN REACTION ARE ASSOCIATED WITH MORE SEVERE UPPER RESPIRATORY SYMPTOMS AND ABDOMINAL PAIN

  • The predominant yeast present in the small intestine is Candida.
  • >103 yeast/mL in the small intestine, correlates with greater severity of abdominal pain and straining, while >104 correlates with greater upper respiratory and esophageal symptoms.