Dysbiosis of the salivary microbiota in pediatric-onset primary sclerosing cholangitis and its potential as a biomarker

Iwasawa, Kentaro; Suda, Wataru; Tsunoda, Tomoyuki; Oikawa-Kawamoto, Manari; Umetsu, Shuichiro; Takayasu, Lena; Inui, Ayano; Fujisawa, Tomoo; Morita, Hidetoshi; Sogo, Tsuyoshi; Hattori, Masahira

doi:10.1038/s41598-018-23870-w

Cited by 54 publications

(46 citation statements)

References 50 publications

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“…More recently, the first data on the salivary microbiome in patients with PSC was reported, based on a cohort of newly diagnosed, paediatric PSC patients from Japan, where faecal microbiota composition was in line with the description above . The salivary microbiome was characterized by changes in bacterial taxa that mirror the findings from faecal microbiota, with Haemophilus spp , Veillonella spp and Streptococcus spp being different between paediatric PSC patients and age‐matched controls.…”

Section: Introductionmentioning

confidence: 53%

The gut microbial influence on cholestatic liver disease

Kummen

Hov

2019

Liver International

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Patients with cholestatic liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) have a different gut microbiome composition than healthy controls. In contrast with PBC, PSC has a strong association with inflammatory bowel disease and is the prototypical disease of the gut‐liver axis. Still, there are some distinct overlapping microbial features in the microbiome of patients with PSC and PBC suggesting similarities in cholestatic diseases, although the possible pathogenetic involvement of these shared microbial changes is unknown. Herein, we present an overview of the available data and discuss the relevance for potential disease relevant host‐microbiota interactions. In general, the microbiome interacts with the host via the immunobiome (interactions between the host immune system and the gut microbiome), the endobiome (where the gut microbiome contributes to host physiology by producing or metabolizing endogenous molecules) and the xenobiome (gut microbial transformation of exogenous compounds, including nutrients and drugs). Experimental and human observational evidence suggest that the presence and functions of gut microbes are relevant for the severity and progression of cholestatic liver disease. Interestingly, the majority of new drugs that are currently being tested in PBC and PSC in clinical trials act on bile acid homeostasis, where the endobiome is important. In the future, it will be paramount to perform longitudinal studies, through which we can identify new intervention targets, biomarkers or treatment‐stratifiers. In this way, gut microbiome‐based clinical care and therapy may become relevant in cholestatic liver disease within the foreseeable future.

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Section: Introductionmentioning

confidence: 53%

The gut microbial influence on cholestatic liver disease

Kummen

Hov

2019

Liver International

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“…Provided that our results are confirmed by others, one can envision using faecal microbiota-based biomarkers as a diagnostic tool in patients with suspected PSC. This type of strategy has already been proposed,13 16 18 notably by Iwasawa et al who recently reported a characteristic dysbiosis of the salivary microbiota in children with PSC 47. Furthermore, specific alterations of the gut microbiota found in PSC could be used to design new therapeutic strategies, as recently proposed for alcoholic liver disease 48…”

Section: Discussionmentioning

confidence: 96%

Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis

Lemoinne¹,

Kemgang²,

Belkacem³

et al. 2019

Gut

150

134

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ObjectivePatients with primary sclerosing cholangitis (PSC) were previously shown to display a bacterial gut dysbiosis but fungal microbiota has never been examined in these patients. The aim of this study was to assess the fungal gut microbiota in patients with PSC.DesignWe analysed the faecal microbiota of patients with PSC and concomitant IBD (n=27), patients with PSC and no IBD (n=22), patients with IBD and no PSC (n=33) and healthy subjects (n=30). Bacterial and fungal composition of the faecal microbiota was determined using 16S and ITS2 sequencing, respectively.ResultsWe found that patients with PSC harboured bacterial dysbiosis characterised by a decreased biodiversity, an altered composition and a decreased correlation network density. These alterations of the microbiota were associated with PSC, independently of IBD status. For the first time, we showed that patients with PSC displayed a fungal gut dysbiosis, characterised by a relative increase in biodiversity and an altered composition. Notably, we observed an increased proportion of Exophiala and a decreased proportion of Saccharomyces cerevisiae. Compared with patients with IBD and healthy subjects, the gut microbiota of patients with PSC exhibited a strong disruption in bacteria-fungi correlation network, suggesting an alteration in the interkingdom crosstalk.ConclusionThis study demonstrates that bacteria and fungi contribute to gut dysbiosis in PSC.

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“…No relation between Oribacterium and NAFLD has been described to date. Nonetheless, this genus could be related to liver disease as increased relative abundance of Oribacterium has been found in salivary microbiota of primary sclerosing cholangitis patients . On the contrary, Oscillospira has been related to a healthy metabolic profile, being diminished in obese adults and pediatric NAFLD patients …”

Section: Discussionmentioning

confidence: 99%

A Network Involving Gut Microbiota, Circulating Bile Acids, and Hepatic Metabolism Genes That Protects Against Non‐Alcoholic Fatty Liver Disease

Petrov

García‐Mediavilla

Guzmán

et al. 2019

Molecular Nutrition Food Res

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Scope Gut microbiota contributes to non‐alcoholic fatty liver disease (NAFLD) pathogenesis by multiple mechanisms not yet completely understood. Novel differential features between germ‐free mice (GFm) transplanted with protective or non‐protective cecal microbiota against NAFLD are investigated. Methods and results Gut microbiota composition, plasma, and fecal bile acids (BAs) and liver mRNAs are quantified in GFm recipients from four donor mice differing in NAFLD severity (control diet, high‐fat diet [HFD]‐responder, HFD‐non‐responder, and quercetin‐supplemented HFD). Transplanted GFm are on control or HFD for 16‐weeks. Multivariate analysis shows that GFm colonized with microbiota from HFD‐non‐responder and quercetin supplemented‐HFD donors (protected against NAFLD) clusters together, whereas GFm colonized with microbiota from control and HFD‐responder mice (non‐protected against NAFLD) establishes another cluster. Protected phenotype is associated with increased gut Desulfovibrio and Oscillospira, reduced gut Bacteroides and Oribacterium, lower primary and higher secondary BAs in plasma and feces, induction of hepatic BA transporters, and repression of hepatic lipogenic and BA synthesis genes. Conclusion Protective gut microbiota associates with increased specific secondary BAs, which likely inhibit lipogenic pathways and enhance bile flow in the liver. This novel cross‐talk between gut and liver, via plasma BAs, that promotes protection against NAFLD may have clinical and nutritional relevance.

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Dysbiosis of the salivary microbiota in pediatric-onset primary sclerosing cholangitis and its potential as a biomarker

Cited by 54 publications

References 50 publications

The gut microbial influence on cholestatic liver disease

The gut microbial influence on cholestatic liver disease

Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis

A Network Involving Gut Microbiota, Circulating Bile Acids, and Hepatic Metabolism Genes That Protects Against Non‐Alcoholic Fatty Liver Disease

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