Treatment with phenylbutyrate in a pre-clinical trial reduces diarrhea due to enteropathogenic Escherichia coli: link to cathelicidin induction

Al-Mamun, Abdullah; Mily, Akhirunnessa; Sarker, Protim; Tiash, Snigdha; Navarro, Armando; Akter, Mahmuda; Talukder, Kaisar A.; Islam, Mohammad Faizul; Agerberth, Birgitta; Guðmundsson, Guðmundur H.; Cravioto, Alejandro; Raqib, Rubhana

doi:10.1016/j.micinf.2013.08.007

Cited by 23 publications

(21 citation statements)

References 40 publications

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“…In our study, histopathological features in the ileum were similar to those previously described (Al-Mamun et al, 2013). Normal intestinal barriers are breached by pathogenic E. coli colonization; then bacteria and their products, such as LPS, infiltrate into blood and recruit polymorphonuclear (PMN) leukocytes.…”

Section: Discussionsupporting

confidence: 89%

“…Normal intestinal barriers are breached by pathogenic E. coli colonization; then bacteria and their products, such as LPS, infiltrate into blood and recruit polymorphonuclear (PMN) leukocytes. Moreover, as reported previously (Gallois et al, 2007; Al-Mamun et al, 2013), growth performances of rabbits are retarded by the infection. And, in our case, the retardation was caused by the decrease in the feed conversion ratio as the feed supply was constant.…”

Section: Discussionsupporting

confidence: 83%

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Efficacy of Phage Therapy in Controlling Rabbit Colibacillosis and Changes in Cecal Microbiota

et al. 2017

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Phage therapy is a valid weapon that we could use to fight against pathogens. Bacteriophages kill bacteria and self-proliferate in the digestive tract. Furthermore, it was assumed that phage therapy could preserve the existing gut microbiota. In this study, 45 rabbits were equally divided into three groups after they were orally inoculated with pathogenic Escherichia coli to induce gut infection. Each group was treated with bacteriophage ZRP1 (Group P), ciprofloxacin lactate (Group A), or phosphate-buffered solution (PBS) (Group N). Another 15 healthy rabbits composed the control group (Group C). The body weight gain decreased significantly, but the white blood cell (WBC) count, especially the percentage of large WBCs, and the serum endotoxin levels increased significantly after infection. The result of microscopic examination of the ileum showed that E. coli ZR1 adhered to villi and caused hemorrhage inside the villi. Groups P and A rabbits recovered after treatments, and both bacteriophage and antibiotic treatment significantly decreased the eaeA gene concentration in cecal contents. The microbiota in cecal contents changed in infected rabbits that were treated with PBS. The relative abundance of Clostridiales and YS2 decreased but the relative abundance of Enterobacteriales increased significantly. According to the principal components analysis, the microbiota of Groups P and C rabbits were similar to one another in type and relative abundance but different from those of Groups N and A rabbits. The results demonstrated that oral administration of bacteriophage can cure gut infection with minimal impact on the cecal microbiota.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 83%

Efficacy of Phage Therapy in Controlling Rabbit Colibacillosis and Changes in Cecal Microbiota

et al. 2017

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“…In addition, 1,25-Dihydroxyvitamin D3 (vitD) enhances the expression of LL-371617 and in a synergistic manner with PBA15. Induction by butyrate or PBA resulted in pathogen elimination and improved clinical symptoms in a rabbit model of shigellosis1819 and of enteropathogenic E. coli (EPEC) induced diarrhea20. Adjunct therapy of PBA and vitD together with conventional TB antibiotics demonstrated beneficial effects towards clinical recovery in tuberculosis21.…”

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confidence: 99%

Potent Inducers of Endogenous Antimicrobial Peptides for Host Directed Therapy of Infections

Ottosson

Nylén

Sarker

et al. 2016

Sci Rep

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A new concept for treatment of infections is induction of our own antimicrobial peptides and the presented novel class of inducer, aroylated phenylenediamines (APDs), gives up to 20 to 30-fold induction of the human antimicrobial peptide LL-37, in vitro. In addition, oral administration of an APD in a rabbit model of Shigellosis resulted in recovery from the infection in a few days implying that APD’s are promising candidates for treatment of infections.

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“…Besides, in polarized human intestinal cells, Shigella flexneri suppressed LL-37 and HBD-3 (11). In an experimental model of diarrhea induced by enteropathogenic Escherichia coli (EPEC), we showed the downregulation of CAP-18, a rabbit homologue of LL-37, in intestinal epithelia (12). Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) have been shown to suppress CAP-18 and the mouse cathelicidin mCRAMP in the ileal mucosae of rabbits and mice, respectively (13).…”

mentioning

confidence: 84%

“…A novel therapeutic approach would be to compensate for the loss of AMPs by inducing their production at local sites of infection. Indeed, we have shown that treatment of Shigella-or EPEC-infected rabbits with sodium butyrate and/or its analogue phenylbutyrate induces CAP-18 in the intestinal epithelia, which is associated with improved clinicopathological features (12,15,16). We also conducted a clinical trial with Shigella-infected patients, where the use of butyrate simultaneously enhanced LL-37 expression and reduced the local inflammation of the large intestine (17).…”

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confidence: 99%

Treatment with Entinostat Heals Experimental Cholera by Affecting Physical and Chemical Barrier Functions of Intestinal Epithelia

Sarker

Banik

Strömberg

et al. 2017

Antimicrob Agents Chemother

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We have shown previously that oral treatment with sodium butyrate or phenylbutyrate in an experimental model of shigellosis improves clinical outcomes and induces the expression of the antimicrobial peptide CAP-18 in the large intestinal epithelia. In a subsequent study, we found that entinostat, an aroylated phenylenediamine compound, has similar therapeutic potential against shigellosis. In this study, we aimed to evaluate entinostat as a potential candidate for host-directed therapy against cholera in an experimental model. Vibrio cholerae-infected rabbits were treated with two different dose regimens of entinostat: either 0.5 mg twice daily for 2 days or 1 mg once daily for 2 days. The effects of treatment on clinical outcomes and V. cholerae shedding (CFU count in stool) were observed. Immunohistochemical analysis was carried out to assess CAP-18 expression in ileal and jejunal mucosae. The serum zonulin level was measured by an enzyme-linked immunosorbent assay (ELISA) to evaluate gut permeability. Infection of rabbits with V. cholerae downregulated CAP-18 expression in the ileal epithelium; the expression was replenished by oral treatment with entinostat at either dose regimen. The level of zonulin, a marker of gut permeability, in serum was upregulated after infection, and this upregulation was counteracted after treatment with entinostat. Entinostat treatment also led to recovery from cholera and a decline in the V. cholerae count in stool. In conclusion, the improved clinical outcome of cholera for rabbits treated with entinostat is associated with the induction of CAP-18 and the reduction of gut epithelial permeability.

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Treatment with phenylbutyrate in a pre-clinical trial reduces diarrhea due to enteropathogenic Escherichia coli: link to cathelicidin induction

Cited by 23 publications

References 40 publications

Efficacy of Phage Therapy in Controlling Rabbit Colibacillosis and Changes in Cecal Microbiota

Efficacy of Phage Therapy in Controlling Rabbit Colibacillosis and Changes in Cecal Microbiota

Potent Inducers of Endogenous Antimicrobial Peptides for Host Directed Therapy of Infections

Treatment with Entinostat Heals Experimental Cholera by Affecting Physical and Chemical Barrier Functions of Intestinal Epithelia

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