Hepatocellular Carcinoma: Understanding the Inflammatory Implications of the Microbiome

Khalyfa, Ahamed; Punatar, Shil; Yarbrough, Alex

doi:10.3390/ijms23158164

Cited by 9 publications

(6 citation statements)

References 100 publications

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“…Microbiota transplantation from HCC donors altered gut microbiota profiles, notably hydrogen sulfide-producing taxa ( i.e. , Desulfovibrio , Bilophila ) linked to colorectal and liver cancer ( 78 , 79 ). Recently, microbial-derived hydrogen sulfide was reported to activate vagal afferents via modulation of calcium-selective vagal receptors ( 58 ), highlighting a possible mechanism for HCC-induced vagal-brain signaling.…”

Section: Discussionmentioning

confidence: 99%

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Bauer,

Trehan,

Ruf

et al. 2024

Preprint

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Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8+ T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.

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Section: Discussionmentioning

confidence: 99%

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Bauer,

Trehan,

Ruf

et al. 2024

Preprint

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“…identified from the ICC of the sandhill crane was an opportunistic or secondary infection together with E. coli, it may have induced an inflammatory process in its liver, and it seems likely that it played a role in exacerbating the cirrhosis associated with hepatic fibrogenesis. The inflammatory process may also be a reactive change secondary to tissue damage by neoplastic cells [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Intrahepatic Cholangiocarcinoma Identified in a Zoo-Housed Sandhill Crane (Grus canadensis): An Anatomopathological and Metagenomic Study

Kim,

Kwon

2023

Animals

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Tumors in birds can be caused by a variety of factors such as species, age, sex, virus, chemicals, and environment. In particular, tumors are a major cause of death in long-lived birds such as parrots and zoo birds. A male sandhill crane that was bred for 8 years in a zoo was diagnosed with intrahepatic cholangiocarcinoma (ICC). At necropsy, the liver revealed a multinodular mass of variable colors, and severe cirrhosis and hemorrhages were present. Histologically, ICC was characterized by the presence of both types of ICC: small-duct type and large-duct type. Large-duct-type ICC was distinguished by the presence of multifocal biliary neoplasia, characterized by the diffuse papillary proliferation of columnar cells resembling large cholangiocytes. Small-duct-type ICC was characterized by the presence of non-mucin-producing cuboidal cells such as bile duct cells. In this case, no viral cause was identified from the metagenomic analysis and PCR of ICC; however, a contributing role of Cutibacterium sp. and E. coli identified from the metagenomics could not be excluded. This study is the first to describe the anatomopathological characteristics of ICC in the studied sandhill crane and attempts to determine its potential infectious etiology using metagenomics.

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“…It is clearly established that the gut microbiome may influence the induction and progression of HCC by interfering with immune and metabolic pathways related to HCC. Data, both experimental [310] and clinical, mostly exists for non-viral HCC [311][312][313][314][315]. Recent findings have demonstrated that this is also true for HBV related HCC.…”

Section: Hbv-related Hccmentioning

confidence: 98%

Viral Liver Disease and Intestinal Gut–Liver Axis

Kouroumalis,

Tsomidis,

Voumvouraki

2024

Gastrointestinal Disorders

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The intestinal microbiota is closely related to liver diseases via the intestinal barrier and bile secretion to the gut. Impairment of the barrier can translocate microbes or their components to the liver where they can contribute to liver damage and fibrosis. The components of the barrier are discussed in this review along with the other elements of the so-called gut–liver axis. This bidirectional relation has been widely studied in alcoholic and non-alcoholic liver disease. However, the involvement of microbiota in the pathogenesis and treatment of viral liver diseases have not been extensively studied, and controversial data have been published. Therefore, we reviewed data regarding the integrity and function of the intestinal barrier and the changes of the intestinal microbioma that contribute to progression of Hepatitis B (HBV) and Hepatitis C (HCV) infection. Their consequences, such as cirrhosis and hepatic encephalopathy, were also discussed in connection with therapeutic interventions such as the effects of antiviral eradication and the use of probiotics that may influence the outcome of liver disease. Profound alterations of the microbioma with significant reduction in microbial diversity and changes in the abundance of both beneficial and pathogenic bacteria were found.

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Hepatocellular Carcinoma: Understanding the Inflammatory Implications of the Microbiome

Cited by 9 publications

References 100 publications

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve

Intrahepatic Cholangiocarcinoma Identified in a Zoo-Housed Sandhill Crane (Grus canadensis): An Anatomopathological and Metagenomic Study

Viral Liver Disease and Intestinal Gut–Liver Axis

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