P3213 - Duodenal Microbial Toxins are Linked to Gastrointestinal Symptoms Severity and Small Intestinal Bacterial Overgrowth

Gabriela Leite, PhD¹, Walter Morales, ¹, Cristina M. Fajardo, MSc¹, Ava Hosseini, MPH¹, Mohamad Rashid, MD¹, Maritza Sanchez, ¹, Stacy Weitsman, MS¹, Gillian M. Barlow, PhD¹, Ruchi Mathur, MD², Ali Rezaie, MD¹, Mark Pimentel, MD^1
1Cedars-Sinai Medical Center, West Hollywood, CA; ²Cedars-Sinai Medical Center, Los Angeles, CA

Introduction: The human gut microbiome plays key roles in health. Besides involvement in metabolic processes, commensals also inhibit the growth of pathogenic microbes. This ability involves virulence factors, such as endotoxins (e.g.lipopolysaccharides) and exotoxins (e.g. cytotoxins, neurotoxins, and enterotoxins). Exotoxins are highly potent and cause damage to the host. Here, we examine the presence of exotoxins using whole genome sequencing of duodenal aspirates and their association with GI symptoms.

Methods: Duodenal luminal samples were obtained from subjects undergoing upper endoscopy without colon prep using a double-lumen protected catheter. Fresh aspirates were plated on MacConkey (MAC) and blood agar to determine the bacterial CFU/mL. DNAs were prepared using the Illumina DNA Prep and Tagmentation kit and sequenced on a NovaSeq 6000 (Illumina). CLC Workbench Metagenomics and Resequencing pipelines and (Qiagen) were used for data analysis. After trimming, de-hosted reads mapped to a microbial index (minimum length of 100 bases) were mapped against 229 exotoxins from the Database of Bacterial ExoToxins for Human Subjects with a positive match to at least one toxin were clustered and compared to those without matches.

Results: 101 subjects were analyzed (females=65%, BMI=25.7 ± 6 kg/m2, age=57.2 ± 14 yrs). A total of 15 exotoxins were identified in duodenal samples (Table 1). Pneumolysin, from Streptococcus pneumoniae, was most prevalent (41.6%), followed by intermedilysin (S. intermedius, 9.9%), SopB (Salmonella enterica subsp. Enterica, 3%), and Hemolysin E (Escherichia coli, 3%) (Table 1). The remaining toxins prevalences appeared highly variable (Table 1). Subjects with duodenal pneumolysin had no differences in GI symptoms severity compared to those without (P=NS for all GI symptoms). Six of the identified exotoxins (40%) were from Gram-negative bacteria (coliforms). Subjects with at least one match to one of these exotoxins were pooled for further analysis (N=9). Subjects with these exotoxins had elevated CFU/mL counts on MAC agar (P< 0.0001). Interestingly, those with these exotoxins appeared to have more diarrhea than those without (P=0.057) and less severe self-reported constipation (P=0.028).

Discussion: Toxins are common in the small bowel. The most prevalent duodenal exotoxin, pneumolysin, is not associated with GI symptoms. In contrast, exotoxins from bacteria usually involved in enterocolitis and bacterial overgrowth appeared to be more associated with diarrhea severity.


Disclosures:


Gabriela Leite, PhD¹, Walter Morales, ¹, Cristina M. Fajardo, MSc¹, Ava Hosseini, MPH¹, Mohamad Rashid, MD¹, Maritza Sanchez, ¹, Stacy Weitsman, MS¹, Gillian M. Barlow, PhD¹, Ruchi Mathur, MD², Ali Rezaie, MD¹, Mark Pimentel, MD¹. P3213 - Duodenal Microbial Toxins are Linked to Gastrointestinal Symptoms Severity and Small Intestinal Bacterial Overgrowth, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.