Protective Effects of ALDH1A Enzyme Inhibition on Helicobacter-Induced Colitis in Smad3−/− Mice are Associated with Altered α4ß7 Integrin Expression on Activated T Cells

Seamons, Audrey; Haenisch, Michael; Meeker, Stacey; Pershutkina, Olesya; Brabb, Thea; Treuting, Piper M.; Paik, Ji-Sun

doi:10.3390/nu12102927

Cited by 6 publications

(14 citation statements)

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“…The potential effectiveness of 5-ASA in producing significant effects through the alleviation of mucosal inflammation has been documented ( 16 – 18 ). Likewise, corticosteroids prove effective in mitigating inflammatory responses, exhibiting immunomodulatory effects and finding extensive applications in treatment ( 19 – 21 ). Glucocorticoids are commonly employed for more severe conditions than those treated with 5-ASA ( 22 ), and their administration may be escalated when 5-ASA treatment proves ineffective ( 23 ).…”

Section: Treatment Methods For Ibdmentioning

confidence: 99%

Advances and optimization strategies in bacteriophage therapy for treating inflammatory bowel disease

Li,

Duan

et al. 2024

Front. Immunol.

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In the advancement of Inflammatory Bowel Disease (IBD) treatment, existing therapeutic methods exhibit limitations; they do not offer a complete cure for IBD and can trigger adverse side effects. Consequently, the exploration of novel therapies and multifaceted treatment strategies provides patients with a broader range of options. Within the framework of IBD, gut microbiota plays a pivotal role in disease onset through diverse mechanisms. Bacteriophages, as natural microbial regulators, demonstrate remarkable specificity by accurately identifying and eliminating specific pathogens, thus holding therapeutic promise. Although clinical trials have affirmed the safety of phage therapy, its efficacy is prone to external influences during storage and transport, which may affect its infectivity and regulatory roles within the microbiota. Improving the stability and precise dosage control of bacteriophages—ensuring robustness in storage and transport, consistent dosing, and targeted delivery to infection sites—is crucial. This review thoroughly explores the latest developments in IBD treatment and its inherent challenges, focusing on the interaction between the microbiota and bacteriophages. It highlights bacteriophages’ potential as microbiome modulators in IBD treatment, offering detailed insights into research on bacteriophage encapsulation and targeted delivery mechanisms. Particular attention is paid to the functionality of various carrier systems, especially regarding their protective properties and ability for colon-specific delivery. This review aims to provide a theoretical foundation for using bacteriophages as microbiome modulators in IBD treatment, paving the way for enhanced regulation of the intestinal microbiota.

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Section: Treatment Methods For Ibdmentioning

confidence: 99%

Advances and optimization strategies in bacteriophage therapy for treating inflammatory bowel disease

Li,

Duan

et al. 2024

Front. Immunol.

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“…The histopathology of H. bilisinduced IBD includes crypt hyperplasia, inflammatory cell infiltrates, crypt abscesses, and obliteration of normal gut architecture. In this study, the relationship between H. bilis and IBD was established by searching in PubMed, MED-LINE, and Web of Science databases, and these results were shown in Table 1 [9,[41][42][43][44][45][46][47][48][49][50][51][52][53]. Some studies clarified how H. bilis promotes IBD occurrence and development; however, few studies have summarized these mechanisms.…”

Section: H Bilis Promotes Ibd Through Inducing Aberrantmentioning

confidence: 99%

“…Various mouse models of IBD include spontaneous colitis models, chemically induced colitis models, colitis in immunodeficient mice, genetically engineered models, or any combination of these models. Recently, a newly identified murine pathogen, Helicobacter bilis ( H. bilis ), has been related to gut infection causing chronic inflammation [ 9 ]. Therefore, H. bilis has been widely used to establish IBD mouse models in many studies, but the mechanism remains unclear [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Nowadays, some studies have explored novel treatments for H. bilis -related IBD. For example, Seamons and collaborators demonstrated that the ALDH1A enzyme could inhibit H. bilis -induced colitis by altering the α 4 β 7 (a gut-homing integrin) expression on activated T cells [ 9 ]. The results of this study provide a new target for the IBD treatment, but its efficacy has only been confirmed in animal models, and further research is urgently needed.…”

Section: Introductionmentioning

confidence: 99%

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Helicobacter bilis Contributes to the Occurrence of Inflammatory Bowel Disease by Inducing Host Immune Disorders

Peng

Zhao

2022

BioMed Research International

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Gut microbiota coevolve with humans to achieve a symbiotic relationship, which ultimately leads to physiological homeostasis. A variety of diseases can occur once this balance is disrupted. Helicobacter bilis (H. bilis) is an opportunistic pathogen in humans, triggering multiple diseases, including inflammatory bowel disease (IBD). IBD is a chronic immunologically mediated inflammation of the human gastrointestinal tract, and its occurrence is closely related to the gut microbiota. Several studies have demonstrated that H. bilis colonization is associated with IBD, and its mechanism is related to host immunity. However, few studies have investigated these mechanisms of action. Therefore, this article is aimed at reviewing these studies and summarizing the mechanisms of H. bilis-induced IBD from two perspectives: adaptive immunity and innate immunity. Furthermore, this study provides a preliminary discussion on treating H. bilis-related IBD. In addition, we also demonstrated that H. bilis played an important role in promoting the carcinogenesis of IBD and discussed its mechanism.

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“…Our group has been using a strong and specific ALDH1A inhibitor, WIN 18,446, to study the role of ALDH1A enzymes in spermatogenesis [ 21 , 22 ]. Our group has also used this inhibitor to study colitis, and showed that WIN 18,446 treatment reduced RA synthesis in vivo and suppressed colitis in an acute mouse model of IBD using Smad3 −/− mice [ 23 ]. WIN 18,446 treatment was associated with the decreased expression of the gut homing α4ß7 integrin on activated CD4 + T cells [ 23 ], which is intriguing because some of the most effective biologics for the treatment of IBD are monoclonal antibodies targeting α4ß7 integrin [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

ALDH1A Inhibition Suppresses Colitis and Alters α4β7 Integrin Expression on Activated T Cells in Mdr1a−/− Mice

Seamons,

Staucean,

Snyder

et al. 2023

Nutrients

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There are limited pharmacological treatment options for inflammatory bowel disease (IBD), and some of these options are expensive and administered by injection or infusion. Thus, new cheaper and easier (oral) treatment options are needed. ALDH1A enzymes produce retinoic acid that can affect intestinal diseases such as IBD by regulating immune cells in the gut. We previously demonstrated that an orally deliverable ALDH1A inhibitor, WIN 18,466, can suppress colitis in an acute mouse model of IBD. Here, we tested the efficacy of ALDH1A inhibition in a chronic mouse model of IBD. Mdr1a−/− mice were treated with a diet containing WIN 18,446 starting 1 week prior to inducing colitis by H. bilis inoculation. Treatment was continued until the study end point and colitis was monitored based on clinical symptoms and confirmed by histological analysis. Immune cell phenotypes in colon-draining lymph nodes (cMLN) were analyzed. WIN 18,446 treatment reduced clinical symptoms and improved histopathologic colitis scores. This was associated with decreased expression of the gut homing integrin, α4β7, on T cells in cMLN; increased expression of CD103, a protein associated with tissue-resident memory T cells; and changes in dendritic cells, plasmacytoid dendritic cells and B cells in inhibitor-treated mice. ALDH1A inhibition broadly influences immune cells during colitis and is a potential new target for IBD treatment. Future studies will be needed to determine the efficacy of ALDH1A inhibition on active colitis and to evaluate its relative efficacy in comparison to approved drugs.

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Protective Effects of ALDH1A Enzyme Inhibition on Helicobacter-Induced Colitis in Smad3−/− Mice are Associated with Altered α4ß7 Integrin Expression on Activated T Cells

Cited by 6 publications

References 50 publications

Advances and optimization strategies in bacteriophage therapy for treating inflammatory bowel disease

Advances and optimization strategies in bacteriophage therapy for treating inflammatory bowel disease

Helicobacter bilis Contributes to the Occurrence of Inflammatory Bowel Disease by Inducing Host Immune Disorders

ALDH1A Inhibition Suppresses Colitis and Alters α4β7 Integrin Expression on Activated T Cells in Mdr1a−/− Mice

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