Gut microbiota and immune system in liver cancer: Promising therapeutic implication from development to treatment

Bartolini, Ilenia; Risaliti, Matteo; Tucci, Rosaria; Muiesan, Paolo; Ringressi, Maria Novella; Taddei, Antonio; Amedei, Amedeo

doi:10.4251/wjgo.v13.i11.1616

Cited by 7 publications

(3 citation statements)

References 111 publications

(181 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Leaky gut is closely linked to and often accompanied by dysbiosis due to mechanisms including imbalanced nutrient absorption, altered mucus layer, and impairment of microbial sensing in host cells (Lobionda et al, 2019;Kinashi and Hase, 2021;Stolfi et al, 2022). Numerous studies have shown the link between dysbiosis and liver disease progression, such as in alcoholic liver disease (Hartmann et al, 2015;Morencos et al, 1995;Hartmann et al, 2013), non-alcoholic fatty liver disease (Panasevich et al, 2017;Raman et al, 2013), non-alcoholic steatohepatitis (Brandl and Schnabl, 2017;Carter et al, 2021), and liver cancer (Zhang et al, 2019;Schneider et al, 2022;Bartolini et al, 2021). The persistently up-regulated MIF signaling in hepatocytes and the resulting pro-inflammatory signatures in macrophages, as well as other cell types including neutrophils, may be from the persistently dysregulated gut environment following early life exposure to BDE-99.…”

Section: Discussionmentioning

confidence: 99%

Single cell transcriptomics unveiled that early life BDE-99 exposure reprogrammed the gut-liver axis to promote a pro-inflammatory metabolic signature in male mice at late adulthood

Lim,

Goedkin,

Jin

et al. 2023

Preprint

View full text Add to dashboard Cite

Polybrominated diphenyl ethers (PBDEs) are a class of legacy flame retardants that bioaccumulate in the environment, raising global health concerns. The gut microbiome is an important regulator of liver including xenobiotic biotransformation, nutrient homeostasis, and immune regulation. Using bulk RNA-Seq, we recently showed that neonatal exposure to BDE-99, a human breast milk-enriched PBDE congener, up-regulated pro-inflammation- and down-regulated drug metabolism-related genes predominantly in males in young adulthood. However, it remains unknown whether such dysregulation persists into late adulthood, how various cell types in the liver contribute to the hepatotoxicity, and to what extent gut microbiome is involved in BDE-99 mediated developmental reprogramming of the liver. To address these knowledge gaps, male C57BL/6 mouse pups were orally exposed to corn oil (10 ml/kg) or BDE-99 (57 mg/kg) once daily from postnatal days 2-4. At 15 months of age, single cell transcriptomics (scRNA-seq) in liver showed that neonatal BDE-99 exposure down-regulated key xenobiotic- and fatty acid metabolizing enzymes and up-regulated genes involved in microbial influx in hepatocytes. Neonatal BDE-99 exposure also led to a persistent increase in the hepatic proportion of neutrophils, a predicted increase of macrophage migration inhibitory factor (MIF) signaling, which activates macrophage populations, as well as histopathological abnormalities of the liver in 15 months of age. The BDE-99 mediated hepatic reprogramming is associated with decreased intestinal tight junction protein (Tjp) transcripts, persistent dysbiosis of the gut microbiome, and dysregulation of inflammation-related fatty acid metabolites. ScRNA-seq in germ-free (GF) mice demonstrated the necessity of a normal gut microbiome in maintaining hepatic immunotolerance. Fecal microbiome transplant to GF mice using large intestinal microbiome from adults that were neonatally exposed to BDE-99 down-regulated Tjp transcripts and up-regulated several cytokines in the large intestine. In conclusion, neonatal BDE-99 exposure reprogrammed the cell type-specific gene expression and cell-cell communication networks in liver towards a pro-inflammation with compromised metabolic functions at late adulthood. Importantly, gut microbiome is necessary in promoting immunotolerance in the liver, and BDE-99-mediated pro-inflammatory signaling may be partly due to the dysregulated gut environment.

show abstract

Section: Discussionmentioning

confidence: 99%

Single cell transcriptomics unveiled that early life BDE-99 exposure reprogrammed the gut-liver axis to promote a pro-inflammatory metabolic signature in male mice at late adulthood

Lim,

Goedkin,

Jin

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…But surgical stress induces dysbiosis, promotes the release of inflammatory cytokines, and increases the permeability of the intestinal barrier, leading to bacterial translocation [21,22]. The liver is exposed to microbiota and microbial metabolites through portal flow, which ultimately leads to increased infection and poor prognosis due to the limited detoxification function of the liver [21,23]. The bidirectional relationship between the gut with its microbiota and the liver is known as the "gut-liver axis" [24].…”

Section: Discussionmentioning

confidence: 99%

Influences of Oral Administration of Probiotics on Posthepatectomy Recovery in Patients in Child-Pugh Grade

Huang

Fang

Jia

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Objective. This study is aimed at investigating the influences of oral administration of probiotics on posthepatectomy recovery in patients in Child-Pugh grade. Methods. 100 patients (50 cases in Child-Pugh A grade and 50 cases in Child-Pugh B grade) underwent hepatectomy in our hospital from January 2018 to January 2020 were involved in this study. Subsequently, Child-Pugh A grade and Child-Pugh B grade patients were set as probiotics group (taking Clostridium butyricum, n = 25 ) and control group (no probiotics, n = 25 ). The general information, infectious indexes, and liver function indexes on days 1, 3, and 5 after operation were collected. Results. In Child-Pugh B grade subgroup patients, the procalcitonin, alanine aminotransferase, and prothrombin time of the probiotics group were statistically significantly lower than that of the control group on days 3 ( P < 0.05 ) and 5 ( P < 0.05 ) after surgery. In Child-Pugh A grade subgroup patients, there were no significant differences between probiotics group and control group after operation. Conclusion. Child-Pugh A grade subgroup patients with hepatectomy could not benefit from oral probiotics. However, Child-Pugh B grade subgroup patients taking probiotics after hepatectomy could reduce postoperative infection and accelerate recovery of liver function.

show abstract

“…For instance, F. nucleatum has been proven to inhibit the T lymphocyte (T-cell) mediated immune responses through the expressions of fibroblast activation protein 2 (Fap2) which binds and activates the inhibitory T cell immunoreceptor with Ig and ITIM domains (TIGIT) on natural killer (NK) cells and T cells [13]. Bacteria colonizing tumors not only influence their growth but also the response to treatment, for example transforming chemotherapy drugs, reprogramming tumor immunity, and influencing immunotherapy response [14,15].…”

Section: Introductionmentioning

confidence: 99%

Utilization of formalin-fixed paraffin-embedded specimens for microbiota characterization in cancer: utility and concern

Gloria

Niccolai

2022

Explor Immunol

View full text Add to dashboard Cite

Microbiome research has enormous potential in cancer research and the use of formalin-fixed paraffin-embedded (FFPE) tissues could offer many advantages. The tumor microenvironment represents a suitable niche for specific microbes and evidence proves the presence of an endogenous tumor microbiota, here referred to as oncobiota. Awareness of the oncobiota role in tumorigenesis could have a large influence on cancer care, in terms of diagnosis, prevention, and treatment. Moreover, understanding the microbial-related tumor microenvironment, and its influence on tumor immune response and cancer cells will help define important pathogenetic mechanisms in cancer starting or progression. Routine collection of histopathological FFPE samples provides a large availability of specimens essential for affordable and impactful retrospective analyses and for getting robust statistical results. The FFPE tissues are common in the analysis of tumor biopsies including the tumor microbiota characterization which has an important role in the modulation of our immune system and consequently of tumor cells. However, the microbiota analysis starting from FFPE tissues presents methodological pitfalls and limits that may negatively affect the oncobiota research. After examining the methodological and analytical difficulties of this approach, this work seeks to offer workable solutions to promote that research area.

show abstract

Gut microbiota and immune system in liver cancer: Promising therapeutic implication from development to treatment

Cited by 7 publications

References 111 publications

Single cell transcriptomics unveiled that early life BDE-99 exposure reprogrammed the gut-liver axis to promote a pro-inflammatory metabolic signature in male mice at late adulthood

Single cell transcriptomics unveiled that early life BDE-99 exposure reprogrammed the gut-liver axis to promote a pro-inflammatory metabolic signature in male mice at late adulthood

Influences of Oral Administration of Probiotics on Posthepatectomy Recovery in Patients in Child-Pugh Grade

Utilization of formalin-fixed paraffin-embedded specimens for microbiota characterization in cancer: utility and concern

Contact Info

Product

Resources

About