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      Therapeutic effects of oral benzoic acid application during acute murine campylobacteriosis

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          Abstract

          Serious risks to human health are posed by acute campylobacteriosis, an enteritis syndrome caused by oral infection with the food-borne bacterial enteropathogen Campylobacter jejuni. Since the risk for developing post-infectious autoimmune complications is intertwined with the severity of enteritis, the search of disease-mitigating compounds is highly demanded. Given that benzoic acid is an organic acid with well-studied health-promoting including anti-inflammatory effects we tested in our present study whether the compound might be a therapeutic option to alleviate acute murine campylobacteriosis. Therefore, microbiota-depleted IL-10 −/− mice were perorally infected with C. jejuni and received benzoic acid through the drinking water from day 2 until day 6 post-infection. The results revealed that benzoic acid treatment did not affect C. jejuni colonization in the gastrointestinal tract, but alleviated clinical signs of acute campylobacteriosis, particularly diarrheal and wasting symptoms. In addition, benzoic acid mitigated apoptotic cell responses in the colonic epithelia and led to reduced pro-inflammatory immune reactions in intestinal, extra-intestinal, and systemic compartments tested on day 6 post-infection. Hence, our preclinical placebo-controlled intervention trial revealed that benzoic acid constitutes a promising therapeutic option for treating acute campylobacteriosis in an antibiotic-independent fashion and in consequence, also for reducing the risk of post-infectious autoimmune diseases.

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          Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis

          The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs.
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            A guide to histomorphological evaluation of intestinal inflammation in mouse models.

            Histomorphology remains a powerful routine evaluating intestinal inflammation in animal models. Emphasizing the focus of a given animal study, histopathology can overstate differences between established models. We aimed to systematize histopathological evaluation of intestinal inflammation in mouse models facilitating inter-study comparisons. Samples of all parts of the intestinal tract from well-established mouse models of intestinal inflammation were evaluated from hematoxylin/eosin-stained sections and specific observations confirmed by subsequent immunohistochemistry. Three main categories sufficiently reflected the severity of histopathology independent of the localization and the overall extent of an inflammation: (i) quality and dimension of inflammatory cell infiltrates, (ii) epithelial changes and (iii) overall mucosal architecture. Scoring schemata were defined along specified criteria for each of the three categories. The direction of the initial hit proved crucial for the comparability of histological changes. Chemical noxes, infection with intestinal parasites or other models where the barrier was disturbed from outside, the luminal side, showed high levels of similarity and distinct differences to changes in the intestinal balance resulting from inside events like altered cytokine responses or disruption of the immune cell homeostasis. With a high degree of generalisation and maximum scores from 4-8 suitable scoring schemata accounted specific histopathological hallmarks. Truly integrating demands and experiences of gastroenterologists, mouse researchers, microbiologists and pathologists we provide an easy-to-use guideline evaluating histomorphology in mouse models of intestinal inflammation. Standard criteria and definitions facilitate classification and rating of new relevant models, allow comparison in animal studies and transfer of functional findings to comparable histopathologies in human disease.
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              Campylobacter jejuni: molecular biology and pathogenesis.

              Campylobacter jejuni is a foodborne bacterial pathogen that is common in the developed world. However, we know less about its biology and pathogenicity than we do about other less prevalent pathogens. Interest in C. jejuni has increased in recent years as a result of the growing appreciation of its importance as a pathogen and the availability of new model systems and genetic and genomic technologies. C. jejuni establishes persistent, benign infections in chickens and is rapidly cleared by many strains of laboratory mouse, but causes significant inflammation and enteritis in humans. Comparing the different host responses to C. jejuni colonization should increase our understanding of this organism.

                Author and article information

                Contributors
                Journal
                Eur J Microbiol Immunol (Bp)
                Eur J Microbiol Immunol (Bp)
                EUJMI
                European Journal of Microbiology & Immunology
                Akadémiai Kiadó (Budapest )
                2062-509X
                2062-8633
                27 May 2024
                September 2024
                : 14
                : 3
                : 243-260
                Affiliations
                [1]Gastrointestinal Microbiology Research Group, Institute of Microbiology, Infectious Diseases and Immunology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , Berlin, Germany
                Author notes
                [* ]Corresponding author. Gastrointestinal Microbiology Research Group, Institute of Microbiology, Infectious Diseases and Immunology, Charité – Universitätsmedizin Berlin, Campus Benjamin Franklin , Hindenburgdamm 30, 12203 Berlin, Germany. Tel.: +49 30 450524318. E-mail: markus.heimesaat@ 123456charite.de
                [†]

                Contributed equally.

                Author information
                https://orcid.org/0000-0001-6399-651X
                Article
                10.1556/1886.2024.00059
                11393648
                38801662
                0f463c88-4a36-4373-ae21-31efbbee0c70
                © 2024 The Author(s)

                Open Access statement. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes – if any – are indicated.

                History
                : 04 May 2024
                : 07 May 2024
                Page count
                Figures: 12, Tables: 1, Equations: 0, References: 88, Pages: 18
                Funding
                Funded by: German Federal Ministries of Education and Research (BMBF)
                Award ID: IP7/01KI2007D
                Funded by: Federal Ministry for Economic Affairs and Energy
                Award ID: ZIM, ZF4117908 AJ8
                Categories
                Article

                benzoic acid,organic acids,enteropathogenic infection,campylobacter jejuni,anti-bacterial effects,anti-inflammatory effects,immune-modulatory effects,secondary abiotic il-10−/− mice,acute campylobacteriosis model,host-pathogen interactions,antibiotics-independent treatment

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