Taniki, Nobuhito



School of Medicine, Department of Internal Medicine (Gastroenterology and Hepatology) (Shinanomachi)


Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)


Papers 【 Display / hide

  • C-C motif chemokine receptor 9 regulates obesity-induced insulin resistance via inflammation of the small intestine in mice

    Amiya T., Nakamoto N., Irie J., Taniki N., Chu P.S., Koda Y., Miyamoto K., Yamaguchi A., Shiba S., Morikawa R., Itoh H., Kanai T.

    Diabetologia (Diabetologia)   2021

    ISSN  0012186X

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    © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature. Aims/hypothesis: Accumulation of adipose tissue macrophages is considered pivotal in the development of obesity-associated inflammation and insulin resistance. In addition, recent studies suggest an involvement of the intestine as the primary organ in inducing hyperglycaemia and insulin resistance. We have reported that the C-C motif chemokine receptor (CCR) CCR9 is associated with intestinal immunity and has a pathogenic role in various liver diseases. However, its contribution to type 2 diabetes is unknown. In the current study, we aimed to clarify the involvement of CCR9 in the pathology of type 2 diabetes and the potential underlying mechanisms. Methods: To elucidate how CCR9 affects the development of metabolic phenotypes, we examined the impact of CCR9 deficiency on the pathogenesis of type 2 diabetes using male C57BL/6J (wild-type [WT]) and CCR9-deficient (CCR9 knockout [KO]) mice fed a 60% high-fat diet (HFD) for 12 weeks. Results: WT and Ccr9KO mice fed an HFD exhibited a comparable weight gain; however, glucose tolerance and insulin resistance were significantly improved in Ccr9KO mice. Moreover, visceral adipose tissue (VAT) and the liver of Ccr9KO mice presented with less inflammation and increased expression of glucose metabolism-related genes than WT mice. Ccr9 and Ccl25 expression were specifically higher in the small intestine but was not altered by HFD feeding and type 2 diabetes development. Accumulation of IFN-γ-producing CD4+ T lymphocytes and increased intestinal permeability in the small intestine was observed in WT mice following HFD feeding, but these changes were suppressed in HFD-fed Ccr9KO mice. Adoptive transfer of gut-tropic CCR9-expressing T lymphocytes partially reversed the favourable glucose tolerance found in Ccr9KO mice via exacerbated inflammation in the small intestine and VAT. Conclusions/interpretation: CCR9 plays a central role in the pathogenesis of type 2 diabetes by inducing an inflammatory shift in the small intestine. Our findings support CCR9 as a new therapeutic target for type 2 diabetes via the gut–VAT–liver axis. Graphical abstract: [Figure not available: see fulltext.]

  • Late-onset acute liver failure due to Wilson's disease managed by plasmapheresis and hemodiafiltration successfully serving as a bridge for deceased donor liver transplantation: a case report and literature review

    Sukezaki, A., Chu, P. S., Shinoda, M., Hibi, T., Taniki, N., Yoshida, A., Kawaida, M., Hori, S., Morikawa, R., Kurokouchi, A., Wakino, S., Kameyama, K., Obara, H., Kitagawa, Y., Saito, H., Kanai, T. and Nakamoto, N.

    Clin J Gastroenterol (Clinical Journal of Gastroenterology)  13 ( 6 ) 1239 - 1246 2020.12

    ISSN  18657257

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    Late-onset acute liver failure due to Wilson's disease (WD-ALF) is rare. A 44-year-old female patient presenting acute hepatic decompensation with extreme coagulopathy was transferred to our hospital for evaluation for liver transplantation (LT). Alveolar hemorrhage and Coombs-negative acute hemolysis occurred during workup. Mechanical ventilation, plasmapheresis, and hemodiafiltration with zinc and chelation were started immediately before placing the patient on the waitlist for deceased donor LT (DDLT), with a tentative diagnosis of WD-ALF using the Leipzig score and quick diagnostic criteria suggested by the Acute Liver Failure Study Group Registry. The peak MELD score was 40, and the revised version of King's score for WD was 13. Serum free copper levels and the patient's overall general condition were stabilized with artificial support systems, although triphasic wave on electroencephalogram and liver atrophy were noted. She successfully underwent emergent DDLT approximately 2 weeks after suffering from acute hemolysis and survived. The genetic tests confirmed mutations at 2 loci in the ATP7B gene and, therefore, the diagnosis of WD. This is the first and oldest patient reported in Japan to present late-onset WD-ALF that was successfully treated with emergent DDLT.

  • Moderate alcohol consumption is not associated with subclinical cardiovascular damage but with hepatic fibrosis in non-alcoholic fatty liver disease

    Kashiwagi, K., Yamaguchi, A., Shiba, S., Taniki, N., Inoue, N., Takaishi, H., Iwao, Y. and Kanai, T.

    Alcohol (Alcohol)  89   1 - 7 2020.12

    ISSN  07418329

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    BACKGROUND: Moderate alcohol consumption is believed to be associated with reduced mortality from cardiovascular disease (CVD) in the general population. This cross-sectional study aimed to comprehensively examine the association between alcohol consumption and subclinical cardiovascular damage or hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD). METHODS: Subjects with NAFLD without a history of heart disease were extracted from 977 consecutive examinees who completed health checkups and optional cardiovascular examinations. Subclinical cardiovascular damage was assessed by coronary artery calcification (CAC), carotid artery ultrasound, and brachial-ankle pulse wave velocity (ba-PWV). CAC scores were classified into three grades (0, </=100, and >100) by Agatston's method. Alcohol consumption was divided into three groups [Non-drinking (G0); Light (G1), 0.1-6.9 drinks/week; Moderate (G2), 7-20.9 drinks/week for men and 7-13.9 drinks/week for women]. Noninvasive markers (FIB-4, Fibrosis-4; NFS, NAFLD fibrosis score) were calculated for assessment of hepatic fibrosis and classified into low and intermediate-high grade. RESULTS: The overall mean age was 60.2 years and males were 200 (74.6%) among 268 subjects with NAFLD. Number (%) of G0, G1, and G2 were 102 (38.1%), 103 (38.4%), and 63 (23.5%). Binary logistic regression analysis showed no significant difference between G0 and G1, or G0 and G2 in any of the above subclinical cardiovascular damages (CAC score >0, or CAC score >100, carotid plaque +, intima-media thickness >/=1.1 mm, and ba-PWV >1400 cm/s). However, only G2 had a significant association with intermediate-high grade of FIB-4 or NFS [odds ratio (95% confidence intervals), p value: 1.871 (1.209-2.893), p = 0.005; 2.910 (1.715-4.939), p = 0.000], compared to G0. CONCLUSIONS: Non-heavy drinking might not reduce the risk of CVD in NAFLD subjects. On the contrary, even moderate drinking could promote hepatic fibrosis. Thus, NAFLD drinkers should not be recommended for even a moderate amount of alcohol.

  • Long-term Observation of Cyclosporine as Second-line Therapy in Adults of Severe Acute Autoimmune Hepatitis

    Noguchi, F., Chu, P. S., Taniki, N., Yoshida, A., Morikawa, R., Yamaguchi, A., Ikura, A., Yamataka, K., Hoshi, H., Usui, S., Ebinuma, H., Saito, H., Kanai, T. and Nakamoto, N.

    Hepatology  2020.10

    ISSN  1527-3350

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    Severe acute-onset autoimmune hepatitis (SA-AIH), a possible cause of acute liver failure (ALF), poses great challenges in diagnosis and management. Latest guidelines and expert reviews advocate a trial of corticosteroids (CS) followed by assessments of their clinical effect for 1-2 weeks with consideration for liver transplantation (LT).

  • The liver-brain-gut neural arc maintains the Treg cell niche in the gut

    Teratani, T., Mikami, Y., Nakamoto, N., Suzuki, T., Harada, Y., Okabayashi, K., Hagihara, Y., Taniki, N., Kohno, K., Sibata, S., Miyamoto, K., Ishigame, H., Chu, P. S., Sujino, T., Suda, W., Hattori, M., Matsui, M., Okada, T., Okano, H., Inoue, M., Yada, T., Kitagawa, Y., Yoshimura, A., Tanida, M., Tsuda, M., Iwasaki, Y. and Kanai, T.

    Nature (Nature)  585 ( 7826 ) 591 - 596 2020.09

    ISSN  00280836

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    The gut-brain axis, a reciprocal interaction between the central nervous system (CNS) and peripheral intestinal functions, is conceptually feasible from recent clinical and experimental evidence showing mutual interactions between the CNS and gut microbiota that are closely associated with the bidirectional effects of inflammatory bowel diseases (IBDs) and CNS disorders(1-4). Despite recent advances in our understanding of neuroimmune interactions, it remains unclear how the gut and brain communicate to maintain gut immune homeostasis, including induction and maintenance of peripheral regulatory T cells (pTreg cells) and what environmental cues prompt the host to protect host from development of IBDs. Here, we report a novel liver-brain-gut neural arc that ensures proper differentiation and maintenance of pTreg cells in the gut. The hepatic vagal sensory afferents were responsible for indirectly sensing the gut microenvironment and relaying the sensory inputs to the nucleus tractus solitarius of the brainstem, and ultimately to the vagal parasympathetic nerves and enteric neurons. Surgical and chemical perturbation of the vagal sensory afferents at the hepatic afferent level significantly impaired colonic pTreg cells, which was attributed to impairment of aldehyde dehydrogenase (ALDH) expression and retinoic acid (RA) synthesis by intestinal antigen-presenting cells (APCs). Muscarinic Ach receptor (mAChR) activation directly induced ALDH gene expression both in human and mouse colonic APCs, whereas genetic ablation of mAChRs abolished APC excitement in vitro. Disruption of left vagal sensory afferents from the liver to the brainstem in colitis models reduced the colonic pTreg pool, resulting in increased susceptibility to colitis. These results demonstrate that the novel vago-vagal liver-brain-gut reflex arc tunes the number of pTreg cells and maintains the gut homeostasis. Intervening in this autonomic feedback feed-forward system could help develop new therapeutic strategies to treat or prevent immunological disorders of the gut.

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  • インジゴ化合物による新規原発性硬化性胆管炎治療法の開発


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

  • 腸肝相関を介した肝免疫寛容誘導機序の解明


    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator


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