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EDITORIAL article

Front. Cell. Infect. Microbiol., 20 January 2023
Sec. Microbiome in Health and Disease
This article is part of the Research Topic Engineering Probiotics for Multiple Interventions on Intestinal Diseases View all 12 articles

Editorial: Engineering probiotics for multiple interventions on intestinal diseases

  • 1Key Laboratory of Systems Bioengineering (Ministry of Education), Frontiers Science Center for Synthetic Biology, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China
  • 2James Watt School of Engineering, University of Glasgow, Glasgow, United Kingdom
  • 3Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, China

Gut microbiota, known as an important “organ” of the human body, plays an important role in regulating the host immune response, repairing the intestinal barrier, and resisting pathogenic bacteria invasion. The imbalance of intestinal microbiota is closely related to digestive system diseases, accelerating the occurrence and development of inflammatory bowel disease (IBD), colorectal cancer (CRC), irritable bowel syndrome (IBS), acute or chronic radiation bowel disease, colonic constipation, diarrhoea and other intestinal diseases. Microecological therapy targeting the structure and function of gut microbiota has attracted extensive attention in the biomedical scientific community (Cani, 2018) . The network meta-analysis (NMA) conducted by Zhang et al. suggested that B.coagulans had prominent efficacy in treating IBS patients. Thus incorporating B.coagulans into a probiotic combination, or genetically engineering the strain to amplify its biological function may be potential routes to treat IBS. Lyu et al. highlighted the mechanisms of SpA by which the gut microbiota impact gut inflammation and trigger the immune responses and discussed the potential of probiotics being an adjunctive therapy for SpA. Hao et al. evaluated the efficacy of probiotics in combination with prebiotics to treat patients suffering from hypothyroidism complications with small intestinal bacterial overgrowth during the second trimester of pregnancy. Yin and Zhu’s systematic review on the meta-analysis of clinical trials suggested probiotics have potential value in the treatment of Parkinson’s disease (PD)-related constipation.

With the development of multi-omics technologies, the genetic and metabolic characteristics of the gut microbiota have been deeply explored to develop new therapeutic interventions for the host (Agrawal et al., 2022). Modelling the spatial interaction network of gut microbiota has been built to reveal the causal relationship between spatial variability and changes in health states (Cao et al., 2022). Intestinal homeostasis is maintained in a dynamic equilibrium by balancing the contribution of different players, including diet and drug use. Traditional Chinese medicine and natural products play an important role in this process. Gut microbiota act as important regulators in inflammation and metabolic disorders (Wang et al., 2021a), relying on microbial metabolites and their interactions with receptors on host cells to activate or inhibit signalling pathways (Wang et al., 2021b). Che et al. elucidated the mechanism of the bidirectional interaction between traditional Chinese medicine and intestinal flora, as well as repairing the intestinal mucosal barrier and protecting the barrier function through various modalities. Thus, multiple interventions based on the modulation of the gut microbiota or the use of specific prebiotics and probiotics might contribute to the design of microecological agents.

Isolating and identifying microbes that can interact with probiotics provides an important basis for evaluating the efficacy of probiotics and clarifying their mechanisms. Yin et al. developed a single-cell droplet approach to obtain the isolates of the beneficial gut bacteria, which complements culture-independent metagenomic investigations of living bacteria therapy. Moreover, emerging technologies, such as Raman spectroscopy, flow cytometry and microfluidic technologies, have provided powerful tools to study microbiome function at the single-cell level (Yuan et al., 2017) and sorting cells (McIlvenna et al., 2016; Lee et al., 2019; Lyu et al., 2020). Wee et al. showed the feasibility of Raman spectroscopy and flow cytometry for phenotypic studies in long-term antibiotic treatment or when investigating new antibiotic classes.

Engineered probiotics are the next generation of live biotherapeutics that have been modified to target specific diseases. In recent years, engineered probiotics served as live biotherapeutics have been continuously created due to the rapid development of synthetic biology (Ozdemir et al., 2018). When disease marker molecules were detected, probiotics were programmed to release therapeutic effectors such as SCFAs (Bai et al., 2020; Wang et al., 2022), 5-HT (Li et al.) and active ingredients from plant sources. In this way, engineered probiotics have been used to improve metabolic disorders, behavioral disorders and cancer efficacy (Gurbatri et al., 2022). In addition to bacteria and fungi, bacteriophage engineering promises to generate phage variants with unique properties for prophylactic and therapeutic applications (Kortright et al., 2019; Dhanoa et al.).Researchers are mining the key components of bacteriophages to build synthetic biological systems (Xu et al., 2020).

The artificial flora designed and synthesized with the concept of synthetic biology is expected to overcome the existing shortcomings and achieve high efficiency, precision and control of microecological therapy (Wang et al.). On the other side, researchers use material or chemical strategies to modify probiotics to achieve therapeutic efficacies for treating intestinal diseases (Song et al., 2022). Fecal Microbiota Transplantation (FMT) is one of the recommended treatments for recurrent Clostridioides diffificile infection, but endoscopy and available oral formulations still have several limitations in their preparation, storage, and administration. Aira et al. used microcrystalline cellulose as the main excipient to maintain the viability of gut microbiota for a long time.

In conclusion, this Research Topic showcases the emerging multidisciplinary approaches, including gene editing, single-cell technology, and faecal microbiota formulation, for engineering and evaluating probiotics as potential therapeutical agents to treat intestinal diseases. We hope that readers find these articles informative and look forward to an exciting future for engineered probiotics.

Author contributions

HH, HY and XZ wrote the manuscript. Both authors read and approved the final manuscript.

Funding

We acknowledge the support from the National Key Research and Development Project (No. 2019YFA0905600), Tianjin Key Research and Development Project (No. 22YFZCSN00090) and EPSRC IAA (EP/X5257161/1 and EP/R511705/1).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Agrawal, M., Allin, K. H., Petralia, F., Colombel, J.-F., Jess, T. (2022). Multiomics to elucidate inflammatory bowel disease risk factors and pathways. Nat. Rev. Gastroenterol. Hepatol. 19, 399–409. doi: 10.1038/s41575-022-00593-y

PubMed Abstract | CrossRef Full Text | Google Scholar

Bai, L., Gao, M., Cheng, X., Kang, G., Cao, X., Huang, H. (2020). Engineered butyrate-producing bacteria prevents high fat diet-induced obesity in mice. Microb. Cell Fact. 19, 94. doi: 10.1186/s12934-020-01350-z

PubMed Abstract | CrossRef Full Text | Google Scholar

Cani, P. D. (2018). Human gut microbiome: Hopes, threats and promises. Gut 67, 1716–1725. doi: 10.1136/gutjnl-2018-316723

PubMed Abstract | CrossRef Full Text | Google Scholar

Cao, X., Dong, A., Kang, G., Wang, X., Duan, L., Hou, H., et al. (2022). Modeling spatial interaction networks of the gut microbiota. Gut Microbes 14, 2106103. doi: 10.1080/19490976.2022.2106103

PubMed Abstract | CrossRef Full Text | Google Scholar

Gurbatri, C. R., Arpaia, N., Danino, T. (2022). Engineering bacteria as interactive cancer therapies. Science 378, 858–864. doi: 10.1126/science.add9667

PubMed Abstract | CrossRef Full Text | Google Scholar

Kortright, K. E., Chan, B. K., Koff, J. L., Turner, P. E. (2019). Phage therapy: A renewed approach to combat antibiotic-resistant bacteria. Cell Host Microbe 25, 219–232. doi: 10.1016/j.chom.2019.01.014

PubMed Abstract | CrossRef Full Text | Google Scholar

Lee, K. S., Palatinszky, M., Pereira, F. C., Nguyen, J., Fernandez, V. I., Mueller, A. J., et al. (2019). An automated raman-based platform for the sorting of live cells by functional properties. Nat. Microbiol. 4, 1035–1048. doi: 10.1038/s41564-019-0394-9

PubMed Abstract | CrossRef Full Text | Google Scholar

Lyu, Y., Yuan, X., Glidle, A., Fu, Y., Furusho, H., Yang, T., et al. (2020). Automated raman based cell sorting with 3D microfluidics. Lab. Chip 20, 4235–4245. doi: 10.1039/D0LC00679C

PubMed Abstract | CrossRef Full Text | Google Scholar

McIlvenna, D., Huang, W. E., Davison, P., Glidle, A., Cooper, J., Yin, H. (2016). Continuous cell sorting in a flow based on single cell resonance raman spectra. Lab. Chip 16, 1420–1429. doi: 10.1039/C6LC00251J

PubMed Abstract | CrossRef Full Text | Google Scholar

Ozdemir, T., Fedorec, A. J. H., Danino, T., Barnes, C. P. (2018). Synthetic biology and engineered live biotherapeutics: Toward increasing system complexity. Cell Syst. 7, 5–16. doi: 10.1016/j.cels.2018.06.008

PubMed Abstract | CrossRef Full Text | Google Scholar

Song, W.-F., Yao, W.-Q., Chen, Q.-W., Zheng, D., Han, Z.-Y., Zhang, X.-Z. (2022). In situ bioorthogonal conjugation of delivered bacteria with gut inhabitants for enhancing probiotics colonization. ACS Cent. Sci. 8, 1306–1317. doi: 10.1021/acscentsci.2c00533

PubMed Abstract | CrossRef Full Text | Google Scholar

Wang, L., Cheng, X., Bai, L., Gao, M., Kang, G., Cao, X., et al. (2022). Positive interventional effect of engineered butyrate-producing bacteria on metabolic disorders and intestinal flora disruption in obese mice. Microbiol. Spectr. 0, e01147–e01121. doi: 10.1128/spectrum.01147-21

CrossRef Full Text | Google Scholar

Wang, L., Gao, M., Kang, G., Huang, H. (2021a). The potential role of phytonutrients flavonoids influencing gut microbiota in the prophylaxis and treatment of inflammatory bowel disease. Front. Nutr. 8. doi: 10.3389/fnut.2021.798038

CrossRef Full Text | Google Scholar

Wang, Y., Zhang, X., Wang, Y., Zhao, W., Li, H., Zhang, L., et al. (2021b). Application of immune checkpoint targets in the anti-tumor novel drugs and traditional Chinese medicine development. Acta Pharm. Sin. B 11, 2957–2972. doi: 10.1016/j.apsb.2021.03.004

PubMed Abstract | CrossRef Full Text | Google Scholar

Xu, J., Li, X., Kang, G., Bai, L., Wang, P., Huang, H. (2020). Isolation and characterization of AbTJ, an acinetobacter baumannii phage, and functional identification of its receptor-binding modules. Viruses 12, 205. doi: 10.3390/v12020205

PubMed Abstract | CrossRef Full Text | Google Scholar

Yuan, X., Couto, J. M., Glidle, A., Song, Y., Sloan, W., Yin, H. (2017). Single-cell microfluidics to study the effects of genome deletion on bacterial growth behavior. ACS Synth. Biol. 6, 2219–2227. doi: 10.1021/acssynbio.7b00177

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: engineered probiotic, host-bacterial interaction, single-cell analysis, intestinal diseases, synthetic biology

Citation: Huang H, Yin H and Zhang X (2023) Editorial: Engineering probiotics for multiple interventions on intestinal diseases. Front. Cell. Infect. Microbiol. 13:1138998. doi: 10.3389/fcimb.2023.1138998

Received: 06 January 2023; Accepted: 10 January 2023;
Published: 20 January 2023.

Edited and Reviewed by:

Benoit Chassaing, Institut National de la Santé et de la Recherche Médicale (INSERM), France

Copyright © 2023 Huang, Yin and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: He Huang, huang@tju.edu.cn

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.