title: Potential mechanisms of effects of serum-derived bovine immunoglobulin/protein isolate therapy in patients with diarrhea-predominant irritable bowel syndrome.
abstract: Serum-derived bovine immunoglobulin/protein isolate (SBI), an oral nutritional therapy, is efficacious in diverse diarrheal diseases. In an open-label study in 15 patients with irritable bowel syndrome-diarrhea (IBS-D), we evaluated effects of SBI (5.0 g, twice a day) for 8 weeks on safety, on bowel function and abdominal pain, tryptophan metabolism (K:T ratio), intestinal permeability (13C-mannitol and lactulose excretion), bile acid synthesis (fasting serum FGF-19 and C4), duodenal and stool microbiome, and the expression of 90 genes related to inflammation, immune function, and tight junctions in duodenal mucosa. Statistical analysis (paired tests, baseline vs. treatment) was based on intention to treat (ITT) principles. One of 15 Caucasian patients (13F, 2M, age 40.3 ± 2.3y, BMI 34.3 ± 3.0 kg/m2) withdrew without completing studies. There were improvements in stools/day (decrease,P< 0.001), ease of passage (P= 0.035), and evacuation (P= 0.004) with SBI therapy. Worst pain severity was numerically reduced in last 2 weeks' treatment (P= 0.078). Duodenal mucosal mRNA expression; serum C4, FGF-19, and KT ratio; small bowel or colon permeability; and stool microbiome were not significantly different after SBI therapy, compared to baseline. In duodenal brushings, there was considerable microbiota structure difference (βdiversity analysisP= 0.072, UniFrac) and, on taxonomic analysis, increased abundance ofProteobacteria Burkholderiales, Firmicutes Catonella,and unclassified genus organisms with SBI therapy. Thus, SBI therapy for 8 weeks in IBS-D patients is associated with improved bowel function; the mechanism of benefit is unclear, though there were microbiota structure differences in duodenal brushings. Further studies in patients with low-grade inflammation and intestinal barrier dysfunction at baseline are indicated.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota.
authors.forename: Nelson
authors.initials: N
authors.lastname: Valentin
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota camilleri.michael@mayo.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota.
authors.forename: Paula
authors.initials: P
authors.lastname: Carlson
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Harrington
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota.
authors.forename: Deborah
authors.initials: D
authors.lastname: Eckert
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota.
authors.forename: Jessica
authors.initials: J
authors.lastname: O'Neill
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota.
authors.forename: Duane
authors.initials: D
authors.lastname: Burton
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Entera Health Inc., Cary, North Carolina.
authors.forename: Audrey L
authors.initials: AL
authors.lastname: Shaw
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota.
authors.forename: Andres
authors.initials: A
authors.lastname: Acosta
mesh_terms: D015746:Abdominal Pain / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D000818:Animals; D002417:Cattle; D003967:Diarrhea / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D010147:Pain Measurement; D010539:Permeability; D016896:Treatment Outcome
chemical_list: D007136:Immunoglobulins
keywords: Bile acids; gene expression; permeability; tryptophan