Dysbiosis in imiquimod-induced psoriasis alters gut immunity and exacerbates colitis development

Pinget, Gabriela Veronica; Tan, Jian; Ni, Duan; Taitz, Jemma; Daïen, C.; Mielle, Julie; Moore, Robert J.; Stanley, Dragana; Simpson, Stephen J.; King, Nicholas J. C.; Macia, Laurence

doi:10.1016/j.celrep.2022.111191

Cited by 15 publications

(11 citation statements)

References 81 publications

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“…As a result, there is an abnormal increase in succinate levels in patients and mouse models with IBD (21), Crohn's disease (CD) (38), and I/R (11). In addition to gutrelated diseases, similar conditions have been observed in human obese (19), psoriatic mice (43) and diarrheic weaned piglets (44). These ndings suggest that in the presence of metabolic abnormalities and disease, the composition of the gut microbiota is biased towards an increase in succinate-producing bacteria or a decrease in succinate-consuming bacteria, leading to an overall increase in succinate production.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of gut microbiota exacerbates LPS-induced endometritis by producing succinate in mice

Fu,

Qiu,

zhao

et al. 2024

Preprint

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There is increasing evidence suggesting a connection between the gut microbiota and female reproductive diseases, including endometritis. Endometritis not only poses higher health risks to women but also incurs significant economic costs in animals. However, the impact of gut inflammation on the gut microbiota and its role in the development of endometritis is still uncertain. This study aimed to investigate the effects of intestinal microbiota on LPS-induced endometritis in mice. Our findings demonstrate that DSS-induced intestinal inflammation can worsen LPS-induced endometritis in mice, and this effect is dependent on the gut microbiota, as the use of antibiotics to deplete the gut microbiota eliminates this protective effect. Similarly, fecal microbiota transplantation (FMT) from DSS-treated mice (DF) to recipient mice exacerbates LPS-induced endometritis. Furthermore, the depletion of DSS and DF leads to increased levels of fecal succinate compared to controls. Additionally, treatment with succinic acid aggravates LPS-induced endometritis in mice. Mechanistically, depletion of DSS treatment resulted in disruption of the gut barrier and an imbalance of succinate-producing and succinate-consuming bacteria. This imbalance led to the massive production, blood transport, and accumulation of succinate in the uterus via the gut-uterus axis. Consequently, the uterine injury was exacerbated through intestinal succinate, which exacerbates uterine injury by SUCNR 1-dependent promotion of NF-κB activation. Overall, our findings suggest that dysbiosis of the gut microbiota exacerbates LPS-induced endometritis in mice by gut microbiota producing succinate. This identifies gut-derived succinate as a novel target for treating critical endometritis. Furthermore, it indicates that targeting the gut microbiota and its metabolism could be a potential strategy for intervention in endometritis and other infectious diseases.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of gut microbiota exacerbates LPS-induced endometritis by producing succinate in mice

Fu,

Qiu,

zhao

et al. 2024

Preprint

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“…Accordingly, M1 polarized gut macrophages appear to aggravate psoriasiform skin inflammation in imiquimod-treated mice by releasing proinflammatory cytokines [64]. Moreover, imiquimod-treated mice have severe gut dysbiosis accompanied by increased macrophage activation, which has been linked to an increased risk and severity of inflammatory bowel disease [65]. Simultaneously, intestinal dysbiosis that induces M1 polarization of macrophages in various tissues seems to explain the increased incidence of psoriasis in obese patients [66].…”

Section: Impact Of Macrophage Polarization In Other Tissues On Psoria...mentioning

confidence: 99%

Macrophage Functions in Psoriasis: Lessons from Mouse Models

Nazimek,

Bryniarski

2024

IJMS

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Psoriasis is a systemic autoimmune/autoinflammatory disease that can be well studied in established mouse models. Skin-resident macrophages are classified into epidermal Langerhans cells and dermal macrophages and are involved in innate immunity, orchestration of adaptive immunity, and maintenance of tissue homeostasis due to their ability to constantly shift their phenotype and adapt to the current microenvironment. Consequently, both macrophage populations play dual roles in psoriasis. In some circumstances, pro-inflammatory activated macrophages and Langerhans cells trigger psoriatic inflammation, while in other cases their anti-inflammatory stimulation results in amelioration of the disease. These features make macrophages interesting candidates for modern therapeutic strategies. Owing to the significant progress in knowledge, our review article summarizes current achievements and indicates future research directions to better understand the function of macrophages in psoriasis.

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“…Elevated succinate levels induce bacterial stress, thus, triggering increased total intestinal BEV release and increasing host secretory IgA production [34]. High succinate is associated with intestinal inflammation [38], psoriasis [39], and obesity [40], which are characterized by increased gut permeability. However, we found that neither increased succinate nor elevated intestinal BEVs affected gut permeability [34].…”

Section: Environmental Factors Regulating Bev Production In Vivomentioning

confidence: 99%

Diet, commensal microbiota‐derived extracellular vesicles, and host immunity

et al. 2023

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The gut microbiota has co‐evolved with its host, and commensal bacteria can influence both the host's immune development and function. Recently, a role has emerged for bacterial extracellular vesicles (BEVs) as potent immune modulators. BEVs are nanosized membrane vesicles produced by all bacteria, possessing the membrane characteristics of the originating bacterium and carrying an internal cargo that may include nucleic acid, proteins, lipids, and metabolites. Thus, BEVs possess multiple avenues for regulating immune processes, and have been implicated in allergic, autoimmune, and metabolic diseases. BEVs are biodistributed locally in the gut, and also systemically, and thus have the potential to affect both the local and systemic immune responses. The production of gut microbiota‐derived BEVs is regulated by host factors such as diet and antibiotic usage. Specifically, all aspects of nutrition, including macronutrients (protein, carbohydrates, and fat), micronutrients (vitamins and minerals), and food additives (the antimicrobial sodium benzoate), can regulate BEV production. This review summarizes current knowledge of the powerful links between nutrition, antibiotics, gut microbiota‐derived BEV, and their effects on immunity and disease development. It highlights the potential of targeting or utilizing gut microbiota‐derived BEV as a therapeutic intervention.

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Dysbiosis in imiquimod-induced psoriasis alters gut immunity and exacerbates colitis development

Cited by 15 publications

References 81 publications

Dysregulation of gut microbiota exacerbates LPS-induced endometritis by producing succinate in mice

Dysregulation of gut microbiota exacerbates LPS-induced endometritis by producing succinate in mice

Macrophage Functions in Psoriasis: Lessons from Mouse Models

Diet, commensal microbiota‐derived extracellular vesicles, and host immunity

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