The immunological functions of the Appendix: An example of redundancy?

Girard-Madoux, Mathilde J.H.; Agüero, Mercedes Gomez de; Ganal‐Vonarburg, Stephanie C.; Mooser, Catherine; Belz, Gabrielle T.; Macpherson, Andrew J.; Vivier, Éric

doi:10.1016/j.smim.2018.02.005

Cited by 76 publications

(79 citation statements)

References 139 publications

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“…To our knowledge, this is the first study to show an association between appendectomy and a decreased rate of excess exhaled CH 4 . It has been hypothesized that the appendix may serve as a reservoir for the gut microbiome due to its location and shape, making it relatively sheltered from microbial changes that occur in the rest of the colon 19,20 . During diarrhoeal illnesses, the appendix may function to repopulate the gut with its own luminal and mucosal microbiome 19 .…”

Section: Discussionmentioning

confidence: 99%

Comparing the rates of methane production in patients with and without appendectomy: results from a large-scale cohort

Takakura

Singer-Englar³

et al. 2020

Sci Rep

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there is no clear study identifying the microbiome of the appendix. However, in other diverticular conditions, such as diverticulosis, methanogens appear important. We investigated whether patients who had undergone appendectomies had decreased levels of exhaled methane (cH 4). Consecutive patients who underwent breath testing (BT) from November 2005 to October 2013 were deterministically linked to electronic health records. the numbers of patients with cH 4 ≥ 1 ppm (detectable) and ≥ 3 and ≥ 10 ppm (excess) were compared between patients who did and did not undergo appendectomy using a multivariable model adjusted for age and sex. Of the 4977 included patients (48.0 ± 18.4 years, 30.1% male), 1303 (26.2%) had CH 4 ≥ 10 ppm, and 193 (3.9%) had undergone appendectomy. Appendectomy was associated with decreased odds of cH 4 ≥ 1, ≥ 3, and ≥ 10 ppm (ORs (95% CI) = 0.67 (0.47-0.93), p = 0.02; 0.65 (0.46-0.92), p = 0.01; and 0.66 (0.46-0.93), p = 0.02, respectively). Additionally, the percentage of CH 4 producers increased 4-fold from the first to ninth decade of life. This is the first study to report that appendectomy is associated with decreased exhaled cH 4. the appendix may play an active physiologic role as a reservoir of methanogens. The appendix is a narrow vermiform organ connected to the caecum. In humans, it can become inflamed and can be surgically removed without any overt consequences; therefore, it is often thought to be a vestigial organ. Some studies have cast doubt on this theory, arguing its potential role in immune function and maintenance of the gut microbiome. Its immunologic role is evidenced by histologic studies showing that the appendix houses large amounts of lymphoid tissues with both active T cells and B cells 1. It is also a relatively rich source for IgA, and its activity seems to be maintained well into adulthood 2. Moreover, the appendix contains a thick biofilm 3 , in which an abundance of microbes live 4,5. The location and unique shape of the appendix makes it an ideal organ in which commensal organisms can be housed to repopulate the colon after the colonic gut microbiome has been modulated during diarrhoeal illnesses. However, to date, appendectomy has not been linked with an objective and clinically relevant microbial change. Archaea are a unique group of microbes that share some features of bacteria (single circular chromosomes that lack introns with similar post-transcriptional modifications) and eukaryotes (use of histones in DNA packing and similar DNA replication, transcription, and translation mechanics) 6. Most archaea in the human gut have a unique metabolic role in that they produce methane (CH 4) as the end-product of their metabolism 7. Most reduce carbon dioxide in the presence of hydrogen (H 2) to produce CH 4 8. Two strict anaerobic strains of methanogens have been described in the human gut: Methanosphaera stadtmaniae 9 and Methanobrevibacter smithii 10. Methanogens have been associated and/or implicated in numerous human diseases, such as obesity, anorexia, constip...

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Section: Discussionmentioning

confidence: 99%

Comparing the rates of methane production in patients with and without appendectomy: results from a large-scale cohort

Takakura

Singer-Englar³

et al. 2020

Sci Rep

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“…Industrialized countries have a high rate of appendectomies, linked to a hyper reactivity of the immune system towards commensal bacteria [16], that is, the hygiene hypothesis. The exact effect of appendectomy on the constitution of the colon microbiota remains to be elucidated [57]. It would be informative to study the microbial population of the appendix in patients suffering from severe gut disorders to discern if the microbiota of the appendix is also affected.…”

Section: Box 2 the Appendix As A Bacterial Safe Housementioning

confidence: 99%

Bowel Biofilms: Tipping Points between a Healthy and Compromised Gut?

Tytgat

Nóbrega

Oost

et al. 2019

Trends in Microbiology

104

103

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Bacterial communities are known to impact human health and disease. Mixed species biofilms, mostly pathogenic in nature, have been observed in dental and gastric infections as well as in intestinal diseases, chronic gut wounds and colon cancer. Apart from the appendix, the presence of thick polymicrobial biofilms in the healthy gut mucosa is still debated. Polymicrobial biofilms containing potential pathogens appear to be an early-warning signal of developing disease and can be regarded as a tipping point between a healthy and a diseased state of the gut mucosa. Key biofilm-forming pathogens and associated molecules hold promise as biomarkers. Criteria to distinguish microcolonies from biofilms are crucial to provide clarity when reporting biofilm-related phenomena in health and disease in the gut.

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“…The primary lymphoid organs consist of the thymus and the bone marrow while the secondary lymphoid organs consist of lymph nodes, spleen, tonsils, and the mucosa-associated lymphoid tissues such as Peyer's patches [44]. More recently, the appendix has been deemed to be a lymphoid organ capable of carrying out immunological functions [45,46]. For the analysis, we compiled gene expression data ( Supplementary Table S6) from multiple projects including FANTOM5 [47], Genotype-Tissue Expression (GTEx) Project [48], The Human Protein Atlas [49,50], Illumina Body Map [51], NIH Roadmap Epigenomics Mapping Consortium [52] and the ENCODE project [53].…”

Section: Expression Of Dual Specificity Phosphatases and Protein Kinamentioning

confidence: 99%

Dynamics of dual specificity phosphatases and their interplay with protein kinases in immune signaling

Subbannayya

Pinto

Bösl

et al. 2019

Preprint

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Dual specificity phosphatases (DUSPs) have a well-known role as regulators of the immune response through the modulation of mitogen activated protein kinases (MAPKs). Yet the precise interplay between the various members of the DUSP family with protein kinases is not well understood. Recent multi-omics studies characterizing the transcriptomes and proteomes of immune cells have provided snapshots of molecular mechanisms underlying innate immune response in unprecedented detail. In this study, we focused on deciphering the interplay between members of the DUSP family with protein kinases in immune cells using publicly available omics datasets. Our analysis resulted in the identification of potential DUSPmediated hub proteins including MAPK7, MAPK8, AURKA, and IGF1R. Furthermore, we analyzed the association of DUSP expression with TLR4 signaling and identified VEGF, FGFR and SCF-KIT pathway modules to be regulated by the activation of TLR4 signaling. Finally, we identified several important kinases including LRRK2, MAPK8, and cyclin-dependent kinases as potential DUSP-mediated hubs in TLR4 signaling. The findings from this study has the potential to aid in the understanding of DUSP signaling in the context of innate immunity. Further, this will promote the development of therapeutic modalities for disorders with aberrant DUSP signaling.

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The immunological functions of the Appendix: An example of redundancy?

Cited by 76 publications

References 139 publications

Comparing the rates of methane production in patients with and without appendectomy: results from a large-scale cohort

Comparing the rates of methane production in patients with and without appendectomy: results from a large-scale cohort

Bowel Biofilms: Tipping Points between a Healthy and Compromised Gut?

Dynamics of dual specificity phosphatases and their interplay with protein kinases in immune signaling

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