The Intestinal Microbiota Plays a Role in Salmonella-Induced Colitis Independent of Pathogen Colonization

Ferreira, Rosana B. R.; Gill, Navkiran; Willing, Benjamin P.; Antunes, L. Caetano M.; Russell, Sarah; Croxen, Matthew A.; Finlay, B. Brett

doi:10.1371/journal.pone.0020338

Cited by 150 publications

(121 citation statements)

References 46 publications

(53 reference statements)

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“…Studies with monoassociated B. thetaiotaomicron have also demonstrated increased cytokine production (48,65). In contrast, increased MIB has been linked with protection against inflammation with S. Typhimurium colonization (25). Increased MIB in the NHE3 Ϫ/Ϫ intestine may dampen down large-scale inflammatory responses, contributing to the low level of inflammatory Fig.…”

Section: Discussionmentioning

confidence: 99%

Loss of NHE3 alters gut microbiota composition and influencesBacteroides thetaiotaomicrongrowth

Engevik

Aihara

Montrose

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Changes in the intestinal microbiota have been linked to diabetes, obesity, inflammatory bowel disease, and Clostridium difficile ( C. difficile)-associated disease. Despite this, it remains unclear how the intestinal environment, set by ion transport, affects luminal and mucosa-associated bacterial composition. Na+/H+-exchanger isoform 3 (NHE3), a target of C. difficile toxin B, plays an integral role in intestinal Na+ absorption. Thus the NHE3-deficient mouse model was chosen to examine the effect of pH and ion composition on bacterial growth. We hypothesized that ion transport-induced change in the intestinal environment would lead to alteration of the microbiota. Region-specific changes in ion composition and pH correlated with region-specific alteration of luminal and mucosal-associated bacteria with general decreases in Firmicutes and increases in Bacteroidetes members. Bacteroides thetaiotaomicron ( B. thetaiotaomicron) increased in NHE3−/− terminal ileum and was examined in vitro to determine whether altered Na+ was sufficient to affect growth. Increased in vitro growth of B. thetaiotaomicron occurred in 43 mM Na+ correlating with the NHE3−/− mouse terminal ileum [Na+]. NHE3−/− terminal ileum displayed increased fut2 mRNA and fucosylation correlating with B. thetaiotaomicron growth. Inoculation of B. thetaiotaomicron in wild-type and NHE3−/− terminal ileum organoids displayed increased fut2 and fucosylation, indicating that B. thetaiotaomicron alone is sufficient for the increased fucosylation seen in vivo. These data demonstrate that loss of NHE3 alters the intestinal environment, leading to region-specific changes in bacteria, and shed light on the growth requirements of some gut microbiota members, which is vital for creating better treatments of complex diseases with an altered gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Loss of NHE3 alters gut microbiota composition and influencesBacteroides thetaiotaomicrongrowth

Engevik

Aihara

Montrose

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Although the mechanisms by which the microbiota limits S. Typhimurium intestinal colonization are not completely elucidated, it has been shown that specific shifts of the microbiota confer either susceptibility or resistance to colitis (24). Once the infection is established, one arm of the host response that reduces S. Typhimurium dissemination is the production of proinflammatory cytokines such as interleukin 23 (IL-23), which activates intestinal T helper 17 (Th17) cells and ␥␦ T cells to release interleukin 17 (IL-17) (25)(26)(27)(28).…”

mentioning

confidence: 99%

Beneficial Effects of Sodium Phenylbutyrate Administration during Infection with Salmonella enterica Serovar Typhimurium

et al. 2016

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c Sodium phenylbutyrate (PBA) is a derivative of the short-chain fatty acid butyrate and is approved for treatment of urea cycle disorders and progressive familial intrahepatic cholestasis type 2. Previously known functions include histone deacetylase inhibitor, endoplasmic reticulum stress inhibitor, ammonia sink, and chemical chaperone. Here, we show that PBA has a previously undiscovered protective role in host mucosal defense during infection. Administration of PBA to Taconic mice resulted in the increase of intestinal Lactobacillales and segmented filamentous bacteria (SFB), as well as an increase of interleukin 17 (IL-17) production by intestinal cells. This effect was not observed in Jackson Laboratory mice, which are not colonized with SFB. Because previous studies showed that IL-17 plays a protective role during infection with mucosal pathogens, we hypothesized that Taconic mice treated with PBA would be more resistant to infection with Salmonella enterica serovar Typhimurium (S. Typhimurium). By using the streptomycin-treated mouse model, we found that Taconic mice treated with PBA exhibited significantly lower S. Typhimurium intestinal colonization and dissemination to the reticuloendothelial system, as well as lower levels of inflammation. The lower levels of S. Typhimurium gut colonization and intestinal inflammation were not observed in Jackson Laboratory mice. Although PBA had no direct effect on bacterial replication, its administration reduced S. Typhimurium epithelial cell invasion and lowered the induction of the proinflammatory cytokine IL-23 in macrophage-like cells. These effects likely contributed to the better outcome of infection in PBA-treated mice. Overall, our results suggest that PBA induces changes in the microbiota and in the mucosal immune response that can be beneficial to the host during infection with S. Typhimurium and possibly other enteric pathogens. S odium 4-phenylbutyrate (phenylbutyric acid [PBA]) is related to the short-chain fatty acid (SCFA) butyrate, differing by the presence of a phenyl group at the 4 position. PBA is an orphan drug, originally approved for urea cycle disorders (1) and subsequently approved for progressive familial intrahepatic cholestasis type 2 (2). The compound has been used in preclinical and clinical studies as a treatment for a variety of diseases, including other urea cycle disorders (3), spinal muscular atrophy (4), homozygous ␤-thalassemia (5), and cancer (6). Additionally, PBA was shown to be effective in the treatment of neurodegenerative diseases, including Parkinson's disease (7).Recent studies have revealed that PBA also plays a role in the reduction of endoplasmic reticulum (ER) stress caused by the unfolded protein response (UPR), thereby suppressing oxidative stress in several animal models (8-11), including in a mouse colitis model (12). In vitro studies further demonstrated that PBA can suppress the activity of nuclear factor B (NF-B), suggesting anti-inflammatory properties for the compound (13). Moreover, administration of PBA w...

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“…After 8 days of per oral administration, the use of a combination of streptomycin and penicillin caused a signiicant reduction in all bacterial counts measured by FISH and intestinal content analysis (Swann et al [32]). Although almost every ATB treatment induces an increase in pathogenic colonisation, the development of enterocolitis was particularly observed after the use of streptomycin or vancomycin (Ferreira et al [33]). In the current research, three types of mouse models were used to study the interaction between the host and the given bacterium: gnotobiotic, conventional and streptomycin-treated.…”

Section: Doxycyclinementioning

confidence: 99%

Influence of Selected Per Orally Administered ATB on Microflora of GIT in Experimental Animals

Maďar¹,

Tatiana²

2018

Antibiotic Use in Animals

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Composition of gastrointestinal (GIT) microbiota difers in individual parts of GIT. Only 40% of GIT bacteria are cultivable. Fluorescence-in-situ-hybridization (FISH) can detect non-cultivable bacteria. Perorally administered antibiotics (ATB) afect the composition of microbiota in GIT. The absorbed ATB, namely penicillins, tetracyclines, macrolides or luorochinolons, have diferent inluence in comparison with poorly absorbed oral ATB, such as aminoglycosides, aminocoumarines or polypeptides. This efect is due to retention of high concentration of non-absorbed ATB during passage through GIT and their longer inluence on bacteria living in diferent parts of GIT. Study methods were based on scientiic literature review from PubMed, Elsevier databases and Slovak scientiic publications. We searched for publications between years 1980 and 2016, with keywords: ATB, inluence, microbiota, FISH. The literature review focuses on peroral administration of ATB to humans and animals and its potential efect on composition of GIT microbiota. The relevant studies showed that per orally administered ATB produced many important changes in microbiota of GIT. FISH method was more frequently used for screening the normal composition of microbiota than for studying the efects of ATB although there were some studies dealing also with this issue.

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The Intestinal Microbiota Plays a Role in Salmonella-Induced Colitis Independent of Pathogen Colonization

Cited by 150 publications

References 46 publications

Loss of NHE3 alters gut microbiota composition and influencesBacteroides thetaiotaomicrongrowth

Loss of NHE3 alters gut microbiota composition and influencesBacteroides thetaiotaomicrongrowth

Beneficial Effects of Sodium Phenylbutyrate Administration during Infection with Salmonella enterica Serovar Typhimurium

Influence of Selected Per Orally Administered ATB on Microflora of GIT in Experimental Animals

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