Intrahepatic microbes govern liver immunity by programming NKT cells

Leinwand, Joshua; Paul, Benjamin C.; Chen, Ruonan; Xu, Fangxi; Sierra, Maria A.; Paluru, Madan M; Nanduri, Sumant; Alcantara, Carolina G; Shadaloey, Sorin Aa; Yang, Fan; Adam, Salma; Li, Qianhao; Bandel, Michelle; Gakhal, Inderdeep; Appiah, Lara; Guo, Yuqi; Vardhan, Mridula; Flaminio, Zia; Grodman, Emilie R; Mermelstein, Ari; Wang, Wei; Diskin, Brian; Aykut, Berk; Khan, Mohammad Afsar; Werba, Gregor; Pushalkar, Smruti; McKinstry, Mia; Kluger, Zachary; Park, Jaimie J; Hsieh, Brandon; Dancel-Manning, Kristen; Liang, Feng-Xia; Park, James S.; Saxena, Anjana; Li, Xin; Theise, Neil D.; Saxena, Deepak; Miller, George

doi:10.1172/jci151725

Cited by 39 publications

(36 citation statements)

References 76 publications

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“…Furthermore, the bacterial structure and abundance of the GM was higher than that of the bile samples, but the bacterial diversity was lower than that of the bile bacterial community, indicating that some specific microbiota from the bile could colonize the GM and proliferate. In a recent study, the human duodenum and GB microbiome were closely clustered based on the Bray-Curtis dissimilarity matrix, suggesting that the GB microbiome has a close relationship with that of the small intestine ( 31 ). In teleost fish, the gut is roughly divided into three segments: the FG, MG, and HG ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

Gallbladder microbiota in early vertebrates provides evolutionary insights into mucosal homeostasis

et al. 2022

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The gallbladder (GB) microbiota plays critical roles in mammalian metabolism and immune homeostasis, and its relationship with human disease has been extensively studied over the past decade. However, very little is known about the interplay between GB microbiota and the immune functions of teleost fish, the earliest bony vertebrate with a GB. Therefore, this study sought to investigate the composition of the teleost GB microbiota and the potential mechanisms through which it affects mucosal immunity. In our results, we found that the GB mucosa (GM) and bile bacterial community shared a similar microbiological composition with that of the gut mucosa in naïve individuals. IHNV infection induced a profound GB inflammation and disrupted their microbial homeostasis followed by a strong anti-bacterial response. Interestingly, beneficial bacteria from the Lactobacillales order showed a significant increase in the abundance of the bile microbial community, whereas the structure of the Mycoplasmatales order in the gut microbial community was markedly changed. All in all, our study characterized the structure of the GB microbial ecosystem in teleost fish, and the fish GB microbiome shared a high similarity with the gut microbiota. More importantly, our findings offer solid evidence that the teleost GB evolved immune functions to preserve its mucosal microbial homeostasis, suggesting that both the microbiota and mucosal immunity of the GB might have co-evolved in early vertebrates.

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Section: Discussionmentioning

confidence: 99%

Gallbladder microbiota in early vertebrates provides evolutionary insights into mucosal homeostasis

et al. 2022

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“…However, a very recent study demonstrated that the liver of both mice and humans harbors a microbiota, which is distinct from that of the gut. 10 This study suggested that the liver microbiota has dramatic impacts on liver immunity by modulating inflammatory cell recruitment and maturation through their microbiome-derived glycosphingolipids. The influence of this naive liver microbiota on liver regeneration is unknown.…”

Section: Main Textmentioning

confidence: 93%

Microbiota in promoting liver regeneration

Wang¹,

Li²

2022

Cell Reports Medicine

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“…However, most internal organs were long thought to be sterile. It is now broadly accepted that organs linked to the gut system harbor a low biomass of microbiota [ 16 , 25 ]. However, it is unknown whether microbial sites (upper or lower gastrointestinal tract) are associated with the pancreatic microbiome.…”

Section: The Microbiome In Healthy and Tumoral Pancreatic Tissuementioning

confidence: 99%

The Microbiome in PDAC—Vantage Point for Future Therapies?

Pfisterer

Heuer²,

Dang

et al. 2022

Cancers

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Microorganisms have been increasingly implicated in the pathogenesis of malignant diseases, potentially affecting different hallmarks of cancer. Despite the fact that we have recently gained tremendous insight into the existence and interaction of the microbiome with neoplastic cells, we are only beginning to understand and exploit this knowledge for the treatment of human malignancies. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid tumor with limited therapeutic options and a poor long-term survival. Recent data have revealed fascinating insights into the role of the tumoral microbiome in PDAC, with profound implications for survival and potentially therapeutic outcomes. In this review, we outline the current scientific knowledge about the clinical and translational role of the microbiome in PDAC. We describe the microbial compositions in healthy and tumoral pancreatic tissue and point out four major aspects of the microbiome in PDAC: pathogenesis, diagnosis, treatment, and prognosis. However, caution must be drawn to inherent pitfalls in analyzing the intratumoral microbiome. Among others, contamination with environmental microbes is one of the major challenges. To this end, we discuss different decontamination approaches that are crucial for clinicians and scientists alike to foster applicability and physiological relevance in this translational field. Without a definition of an exact and reproducible intratumoral microbial composition, the exploitation of the microbiome as a diagnostic or therapeutic tool remains theoretical.

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Intrahepatic microbes govern liver immunity by programming NKT cells

Cited by 39 publications

References 76 publications

Gallbladder microbiota in early vertebrates provides evolutionary insights into mucosal homeostasis

Gallbladder microbiota in early vertebrates provides evolutionary insights into mucosal homeostasis

Microbiota in promoting liver regeneration

The Microbiome in PDAC—Vantage Point for Future Therapies?

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