Intestinal regulatory T (Treg) cells are critical to maintaining immune tolerance to dietary antigens and gut microbiota. This paper reviews several papers on this topic that were recently published by Japanese researchers. Specifically, Prof. K. Honda and his group have found that commensal microbiota capable of metabolizing butyrate induces the differentiation of colonic Treg cells. In a separate work, Prof. Y. Yokoyama and his group used a novel, culture-independent analytical method (the Yakult Intestinal Flora-Scan) for detection of bacteria in the bloodstream. Their work revealed that bacteremia in invasive surgery patients was ameliorated by synbiotic supplementation; similar results were reported in pediatric surgical cases by Dr. T. Okazaki and his group. This cutting-edge method may lead to the evolution of an altered disease concept; an example of this change is provided by the description of bacteremia in patients with type 2 diabetes, as reported by Dr. J. Sato and her group. In a similar work, Prof. Y. Yamashiro and his group found that infants born by cesarean (C)-section, who typically have gut dysbiosis, exhibit higher carriage of toxigenic Clostridium perfringens. The finding suggests that C-section-born infants may serve as a potential reservoir of this opportunistic pathogen. Another separate work by the laboratory of Dr. K. Yamashiro has revealed that gut dysbiosis is associated with altered metabolism and systemic inflammation in patients with ischemic stroke. These papers are consistent with a study by Prof. N. Sudo and his group, who have made significant progress in research on interaction among the microbiota, gut, and brain.

Keywords:
Gut microbiota, Probiotics, Gut dysbiosis, Bacteremia, Bacterial translocation
1.
Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, Fukuda S, Saito T, Narushima S, Hase K, Kim S, Fritz JV, Wilmes P, Ueha S, Matsushima K, Ohno H, Olle B, Sakaguchi S, Taniguchi T, Morita H, Hattori M, Honda K: Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature 2013; 500: 232–236.
2.
Furusawa Y, Obata Y, Fukuda S, et al: Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 2013; 504: 446–450.
3.
Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, Suda W, Imaoka A, Setoyama H, Nagamori T, Ishikawa E, Shima T, Hara T, Kado S, Jinnohara T, Ohno H, Kondo T, Toyooka K, Watanabe E, Yokoyama S, Tokoro S, Mori H, Noguchi Y, Morita H, Ivanov II, Sugiyama T, Nuñez G, Camp JG, Hattori M, Umesaki Y, Honda K: Th17 cell induction by adhesion of microbes to intestinal epithelial cells. Cell 2015; 163: 367–380.
4.
Matsuda K, Tsuji H, Asahara T, Matsumoto K, Takada T, Nomoto K: Establishment of an analytical system for the human fecal microbiota, based on reverse transcription-quantitative PCR targeting of multicopy rRNA molecules. Appl Environ Microbiol 2009; 75: 1961–1969.
5.
Yokoyama Y, Nishigaki E, Abe T, et al: Randomized clinical trial of the effect of perioperative synbiotics versus no synbiotics on bacterial translocation after esophagectomy. Br J Surg 2014; 101: 189–199.
6.
Sakaguchi S, Saito M, Tsuji H, Asahara T, Takata O, Fujimura J, Nagata S, Nomoto K, Shimizu T: Bacterial rRNA-targeted reverse transcription-PCR used to identify pathogens responsible for fever with neutropenia. J Clin Microbiol 2010; 48: 1624–1628.
7.
Sato J, Kanazawa A, Ikeda F, et al: Gut dysbiosis and detection of “live gut bacteria” in blood of Japanese patients with type 2 diabetes. Diabetes Care 2014; 37: 2343–2350.
8.
Nagpal R, Tsuji H, Takahashi T, et al: Gut dysbiosis following C-section instigates higher colonisation of toxigenic Clostridium perfringens in infants. Benef Microbes 2017; 8: 353–365.
9.
Yamashiro K, Tanaka R, Urabe T, et al: Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke. PLoS One 2017; 12:e0171521.
10.
Okazaki T, Asahara T, Yamataka A, et al: Intestinal microbiota in pediatric surgery cases administered Bifidobacterium breve: a randomized controlled trial. J Pediatr Gastroenterol Nutr 2016; 63: 46–50.
11.
Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK, Al-Soud WA, Sørensen SJ, Hansen LH, Jakobsen M: Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One 2010; 5:e9085.
12.
Nagpal R, Ogata K, Tsuji H, Matsuda K, Takahashi T, Nomoto K, Kawashima K, Nagata S, Yamashiro Y: Differences in intestinal microbiota of infants between vaginal delivery and C-section, in particular alpha-toxigenic and enterotoxigenic C. perfringens. 4th Annual Meeting of the Society of Japan Development Origins of Health and Disease, Tokyo, August 2015.
13.
Nagpal R, Ogata K, Tsuji H, Matsuda K, Takahashi T, Nomoto K, Kawashima K, Nagata S, Yamashiro Y: Differences in intestinal microbiota of infants between vaginal delivery and C-section, in particular alpha-toxigenic and enterotoxigenic C. perfringens. 42nd Annual Meeting of the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition, October 2015.
14.
Darmasseelane K, Hyde MJ, Santhakumaran S, Gale C, Modi N: Mode of delivery and offspring body mass index, overweight and obesity in adult life: a systematic review and meta-analysis. PLoS One 2014; 9:e87896.
15.
Gibbons L, Belizán JM, Lauer JA, Betrán AP, Merialdi M, Althabe F: The global numbers and costs of additionally needed and unnecessary caesarean sections performed per year: overuse as a barrier to universal coverage. World Health Report, Background Paper, No 30, 2010.
16.
Hotamisligil GS: Inflammation and metabolic disorders. Nature 2006; 14: 860–867.
17.
Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, Burcelin R: Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008; 57: 1470–1481.
18.
Welsh P, Lowe GD, Chalmers J, Campbell DJ, Rumley A, Neal BC, MacMahon SW, Woodward M: Associations of proinflammatory cytokines with the risk of recurrent stroke. Stroke 2008; 39: 2226–2230.
19.
Nishino R, Mikami K, Takahashi H, et al: Commensal microbiota modulate murine behaviors in a strictly contamination-free environment confirmed by culture based methods. Neurogastroenterol Motil 2013; 25: 521–528.
© 2017 S. Karger AG, Basel
2017
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.