Probiotic treatment vs empiric oral antibiotics for managing dysbiosis in short bowel syndrome: Impact on the mucosal and stool microbiota, short‐chain fatty acids, and adaptation

Abstract

Background: Infants and children with short bowel syndrome (SBS) are presumed to be at risk of gut microbial dysbiosis with potential sequelae of bacterial overgrowth that include sepsis, D-lactic acidosis, mucosal inflammation, and malabsorption. In neonatal piglets with SBS, we compared intestinal microbial composition, shortchain fatty acids (SCFAs), and adaptation given probiotic (PRO) treatment (Lactobacillus and Bifidobacterium spp) vs oral metronidazole (MET).Methods: Following 75% distal small intestinal resection, piglets were allocated to PRO (500 mg twice a day, n = 7), MET (15 mg/kg twice a day, n = 8), and placebo (PLA) (500 mg twice a day, n = 8). After 10 days of parenteral and enteral nutrition, 16S ribosomal RNA gene amplicon sequencing (colon tissue and stool) was undertaken and SCFA analysis (stool and colon effluent) was performed using gas chromatography.Results: In colon, Shannon diversity was higher for PRO compared with MET and PLA (P = 0.002). PRO and PLA increased abundance of Bacteroidetes species (eg, Bacteroides fragilis) compared with MET (P < 0.001). PRO, compared with PLA, increased abundance of Firmicutes species (eg, Lactobacillus fermentum) (P < 0.001).MET increased abundance of Proteobacteria members, predominately Enterobacteriaceae, compared with PRO (P = 0.004). In stool, microbial findings were similar and SCFA (butyrate) concentrations were highest for PRO (P = 0.003) compared with MET. Conclusion:In pediatric SBS, the empiric use of oral antibiotics, such as MET, is common for presumed clinical consequences of microbial dysbiosis. In this study of SBS piglets, that approach was associated with decreased microbial diversity and increased abundance of potentially inflammatory Proteobacteria. In contrast, a PRO treatment using Lactobacillus and Bifidobacterium spp increased both diversity and SCFAs.

Fecal microbiota transplantation in a rodent model of short bowel syndrome: A therapeutic approach?

“…A very recent study, carried out concurrently to our study, demonstrated that treatment of resected piglets, a model of pediatric SBS, with Lactobacillus and Bifidobacterium spp. increased both the diversity of their microbiota and their fecal SCFA concentrations (Pauline et al, 2022). Reinforcing Firmicutes at the expense of Proteobacteria, in particular by administering lactobacillus strains for which beneficial effects have been demonstrated, could increase diversity and SCFA, reduce possible pro-inflammatory bacterial imprint in SBS subject, limit muscle loss… (Ni et al, 2019;Liu et al, 2021;Giron et al, 2022;Pauline et al, 2022).…”

Dysbiosis and reduced small intestinal function are required to induce intestinal insufficiency in mice

“…Moreover, morphological adaptation in the murine SBS model occurs within the first 2 wk after extended resection ( 11 ). Long-term experiments should demonstrate the stability of the resection-induced changes in the gut microbiota and the ability to improve dysbiosis, for example, by probiotics or their metabolites, in future studies ( 39 , 40 ).…”

Treatment of short bowel syndrome: Breaking the therapeutic ceiling?

“…Because of the limitations in testing for SIBO in the patient with SBS, periodic use of antibiotics may be useful for suspected SIBO, together with avoidance of long‐term acid suppression when possible 2 . Recently, treatment with probiotics (several species of Lactobacillus and Bifidobacterium ) was associated with increased gut microbial diversity and SCFAs in piglets with SBS compared with antibiotics 28 . However, their clinical use has been limited by cases of bacteremia with ingested probiotics in children with SBS receiving parenteral support, which may be due to central line contamination after opening probiotic capsules 29,30 .…”

“…2 Recently, treatment with probiotics (several species of Lactobacillus and Bifidobacterium) was associated with increased gut microbial diversity and SCFAs in piglets with SBS compared with antibiotics. 28 However, their clinical use has been limited by cases of bacteremia with ingested probiotics in children with SBS receiving parenteral support, which may be due to central line contamination after opening probiotic capsules. 29,30 Although the evidence is still insufficient and the efficacy and safety should be further evaluated in children, 31 there are no data regarding probiotic use in adult patients with SBS.…”