Skip to main content

Advertisement

SpringerLink
Log in

Poly-β-hydroxybutyrate alleviated diarrhea and colitis via Lactobacillus johnsonii biofilm-mediated maturation of sulfomucin

  • Research Paper
  • Published:
Science China Life Sciences Aims and scope Submit manuscript

Abstract

Maintainance of sulfomucin is a key end point in the treatment of diarrhea and inflammatory bowel disease (IBD). However, the mechanisms underlying the microbial sense to sulfomucin are poorly understood, and to date, there are no therapies targeting the secretion and maturation of sulfomucin in IBD. Herein, we biosynthesized poly-β-hydroxybutyrate (PHB) and found that PHB could alleviate inflammation caused by diarrhea and colitis by enhancing the differentiation of sulfomucin. Microbiota transplantation and clearance together demonstrate that PHB promoting sulfomucin is mediated by Lactobacillus johnsonii (L. johnsonii). Further studies revealed that PHB provides a favorable niche for L. johnsonii biofilm formation to resist disturbance and support its growth. L. johnsonii-biofilm alleviates colitis by regulating fucose residues to promote goblet cell differentiation and subsequent sulfomucin maturation. Importantly, PHB alleviates colitis by enhancing sulfomucin secretion and maturation in a L. johnsonii-dependent manner. PHB represents a class of guardians, acting as a safe probiotic-biofilm delivery system that significantly promotes probiotic proliferation. Altogether, this study adds weight to the possible role of probiotics and functional materials in the treatment of intestinal inflammation. The application of PHB and biofilm self-coating L. johnsonii carries high translational potential and may be of clinical relevance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aiba, Y., Nakano, Y., Koga, Y., Takahashi, K., and Komatsu, Y. (2015). A highly acid-resistant novel strain of Lactobacillus johnsonii No. 1088 has antibacterial activity, including that against Helicobacter pylori, and inhibits gastrin-mediated acid production in mice. Microbiologyopen 4, 465–474.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Althuri, A., Mathew, J., Sindhu, R., Banerjee, R., Pandey, A., and Binod, P. (2013). Microbial synthesis of poly-3-hydroxybutyrate and its application as targeted drug delivery vehicle. Bioresour Technol 145, 290–296.

    Article  CAS  PubMed  Google Scholar 

  • Alvarado, D.M., Chen, B., Iticovici, M., Thaker, A.I., Dai, N., VanDussen, K.L., Shaikh, N., Lim, C.K., Guillemin, G.J., Tarr, P.I., et al. (2019). Epithelial indoleamine 2,3-dioxygenase 1 modulates aryl hydrocarbon receptor and Notch signaling to increase differentiation of secretory cells and alter mucus-associated microbiota. Gastroenterology 157, 1093–1108.e11.

    Article  CAS  PubMed  Google Scholar 

  • Aslim, B., Calişkan, F., Beyatli, Y., and Gündüz, U. (1998). Poly-β-hydroxybutyrate production by lactic acid bacteria. FEMS Microbiol Lett 159, 293–297.

    Article  CAS  PubMed  Google Scholar 

  • Bergstrom, K., Shan, X., Casero, D., Batushansky, A., Lagishetty, V., Jacobs, J.P., Hoover, C., Kondo, Y., Shao, B., Gao, L., et al. (2020). Proximal colon-derived O-glycosylated mucus encapsulates and modulates the microbiota. Science 370, 467–472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, X., Song, P., Fan, P., He, T., Jacobs, D., Levesque, C.L., Johnston, L. J., Ji, L., Ma, N., Chen, Y., et al. (2018). Moderate dietary protein restriction optimized gut microbiota and mucosal barrier in growing pig model. Front Cell Infect Microbiol 8.

  • Chen, Z., Luo, J., Li, J., Kim, G., Chen, E.S., Xiao, S., Snapper, S.B., Bao, B., An, D., Blumberg, R.S., et al. (2021). Foxo1 controls gut homeostasis and commensalism by regulating mucus secretion. J Exp Med 218.

  • Danese, S., and Fiocchi, C. (2011). Ulcerative colitis. N Engl J Med 365, 1713–1725.

    Article  CAS  PubMed  Google Scholar 

  • Dawson, P.A., Huxley, S., Gardiner, B., Tran, T., McAuley, J.L., Grimmond, S., McGuckin, M.A., and Markovich, D. (2009). Reduced mucin sulfonation and impaired intestinal barrier function in the hyposulfataemic NaS1 null mouse. Gut 58, 910–919.

    Article  CAS  PubMed  Google Scholar 

  • Dedkova, E.N., and Blatter, L.A. (2014). Role of beta-hydroxybutyrate, its polymer poly-beta-hydroxybutyrate and inorganic polyphosphate in mammalian health and disease. Front Physiol 5, 260.

    Article  PubMed  PubMed Central  Google Scholar 

  • Duan, Y., Zhang, Y., Dong, H., Zheng, X., Wang, Y., Li, H., Liu, Q., and Zhang, J. (2017). Effect of dietary poly-β-hydroxybutyrate (PHB) on growth performance, intestinal health status and body composition of Pacific white shrimp Litopenaeus vannamei (Boone, 1931). Fish Shellfish Immunol 60, 520–528.

    Article  CAS  PubMed  Google Scholar 

  • Fre, S., Huyghe, M., Mourikis, P., Robine, S., Louvard, D., and Artavanis-Tsakonas, S. (2005). Notch signals control the fate of immature progenitor cells in the intestine. Nature 435, 964–968.

    Article  CAS  PubMed  Google Scholar 

  • Gendler, S.J., and Spicer, A.P. (1995). Epithelial mucin genes. Annu Rev Physiol 57, 607–634.

    Article  CAS  PubMed  Google Scholar 

  • Han, C., Song, J., Hu, J., Fu, H., Feng, Y., Mu, R., Xing, Z., Wang, Z., Wang, L., Zhang, J., et al. (2021). Smectite promotes probiotic biofilm formation in the gut for cancer immunotherapy. Cell Rep 34, 108706.

    Article  CAS  PubMed  Google Scholar 

  • Healey, G.R., Tsai, K., Schick, A., Lisko, D.J., Cook, L., Vallance, B.A., and Jacobson, K. (2021). Prebiotic enriched exclusive enteral nutrition suppresses colitis via gut microbiome modulation and expansion of anti-inflammatory T cells in a mouse model of colitis. Cell Mol Gastroenterol Hepatol 12, 1251–1266.

    Article  CAS  Google Scholar 

  • Hu, J., Ma, L., Nie, Y., Chen, J., Zheng, W., Wang, X., Xie, C., Zheng, Z., Wang, Z., Yang, T., et al. (2018). A microbiota-derived bacteriocin targets the host to confer diarrhea resistance in early-weaned piglets. Cell Host Microbe 24, 817–832.e8.

    Article  CAS  PubMed  Google Scholar 

  • Johansson, M.E.V., and Hansson, G.C. (2016). Immunological aspects of intestinal mucus and mucins. Nat Rev Immunol 16, 639–649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaakoush, N.O. (2015). Insights into the role of erysipelotrichaceae in the human host. Front Cell Infect Microbiol 5.

  • Kaburagi, T., Yamano, T., Fukushima, Y., Yoshino, H., Mito, N., and Sato, K. (2007). Effect of Lactobacillus johnsonii La1 on immune function and serum albumin in aged and malnourished aged mice. Nutrition 23, 342–350.

    Article  CAS  PubMed  Google Scholar 

  • Kamada, N., Chen, G.Y., Inohara, N., and Núñez, G. (2013). Control of pathogens and pathobionts by the gut microbiota. Nat Immunol 14, 685–690.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaser, A., Niederreiter, L., and Blumberg, R.S. (2011). Genetically determined epithelial dysfunction and its consequences for microflora-host interactions. Cell Mol Life Sci 68, 3643–3649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, Y.Y., Mahendra Raj, S., and Graham, D.Y. (2013). Helicobacter pylori infection—a boon or a bane: lessons from studies in a low-prevalence population. Helicobacter 18, 338–346.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lian, Q., Yan, S., Yin, Q., Yan, C., Zheng, W., Gu, W., Zhao, X., Fan, W., Li, X., Ma, L., et al. (2021). TRIM34 attenuates colon inflammation and tumorigenesis by sustaining barrier integrity. Cell Mol Immunol 18, 350–362.

    Article  CAS  PubMed  Google Scholar 

  • Liang, W., Peng, X., Li, Q., Wang, P., Lv, P., Song, Q., She, S., Huang, S., Chen, K., Gong, W., et al. (2020). FAM3D is essential for colon homeostasis and host defense against inflammation associated carcinogenesis. Nat Commun 11, 5912.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liao, X., Zhao, Z., Li, H., Wu, B., Huo, J., Li, L., Li, X., Cao, X., Xia, M., Wang, C., et al. (2022). Fullerene nanoparticles for the treatment of ulcerative colitis. Sci China Life Sci 65, 1146–1156.

    Article  CAS  PubMed  Google Scholar 

  • Liu, P., Zhao, J., Wang, W., Guo, P., Lu, W., Wang, C., Liu, L., Johnston, L. J., Zhao, Y., Wu, X., et al. (2018). Dietary corn bran altered the diversity of microbial communities and cytokine production in weaned pigs. Front Microbiol 9.

  • Ma, N., Chen, X., Liu, C., Sun, Y., Johnston, L.J., and Ma, X. (2022a). Dietary nutrition regulates intestinal stem cell homeostasis. Crit Rev Food Sci Nutr doi: https://doi.org/10.1080/10408398.2022.2087052.

  • Ma, N., He, T., Johnston, L.J., and Ma, X. (2020). Host-microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling. Gut Microbes 11, 1203–1219.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma, N., Sun, Y., Chen, J., Qi, Z., Liu, C., and Ma, X. (2022b). Microcoevolution of genetics rather than diet with enterotype in pigs. Front Nutr 9.

  • McCauley, H.A., and Guasch, G. (2015). Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia. Trends Mol Med 21, 492–503.

    Article  CAS  PubMed  Google Scholar 

  • McDole, J.R., Wheeler, L.W., McDonald, K.G., Wang, B., Konjufca, V., Knoop, K.A., Newberry, R.D., and Miller, M.J. (2012). Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine. Nature 483, 345–349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Możejko-Ciesielska, J., and Kiewisz, R. (2016). Bacterial polyhydroxyalkanoates: still fabulous? Microbiol Res 192, 271–282.

    Article  PubMed  Google Scholar 

  • Neurath, M.F. (2019). Targeting immune cell circuits and trafficking in inflammatory bowel disease. Nat Immunol 20, 970–979.

    Article  CAS  PubMed  Google Scholar 

  • Nhan, D.T., Wille, M., De Schryver, P., Defoirdt, T., Bossier, P., and Sorgeloos, P. (2010). The effect of poly β-hydroxybutyrate on larviculture of the giant freshwater prawn Macrobrachium rosenbergii. Aquaculture 302, 76–81.

    Article  CAS  Google Scholar 

  • Nowarski, R., Jackson, R., Gagliani, N., de Zoete, M.R., Palm, N.W., Bailis, W., Low, J.S., Harman, C.C.D., Graham, M., Elinav, E., et al. (2015). Epithelial IL-18 equilibrium controls barrier function in colitis. Cell 163, 1444–1456.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren, W., Wang, P., Yan, J., Liu, G., Zeng, B., Hussain, T., Peng, C., Yin, J., Li, T., Wei, H., et al. (2018). Melatonin alleviates weanling stress in mice: Involvement of intestinal microbiota. J Pineal Res 64, e12448.

    Article  Google Scholar 

  • Shan, M., Gentile, M., Yeiser, J.R., Walland, A.C., Bornstein, V.U., Chen, K., He, B., Cassis, L., Bigas, A., Cols, M., et al. (2013). Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science 342, 447–453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shroyer, N.F., Wallis, D., Venken, K.J.T., Bellen, H.J., and Zoghbi, H.Y. (2005). Gfi1 functions downstream of Math1 to control intestinal secretory cell subtype allocation and differentiation. Genes Dev 19, 2412–2417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song, Q., Zheng, C., Jia, J., Zhao, H., Feng, Q., Zhang, H., Wang, L., Zhang, Z., and Zhang, Y. (2019). A probiotic spore-based oral autonomous nanoparticles generator for cancer therapy. Adv Mater 31, 1903793.

    Article  CAS  Google Scholar 

  • Sui, L., Cai, J., Sun, H., Wille, M., and Bossier, P. (2012). Effect of poly-β-hydroxybutyrate on Chinese mitten crab, Eriocheir sinensis, larvae challenged with pathogenic Vibrio anguillarum. J Fish Dis 35, 359–364.

    Article  CAS  PubMed  Google Scholar 

  • Sui, L., Liu, Y., Sun, H., Wille, M., Bossier, P., and De Schryver, P. (2014). The effect of poly-β-hydroxybutyrate on the performance of Chinese mitten crab (Eriocheir sinensis Milne-Edwards) zoea larvae. Aquac Res 45, 558–565.

    Article  CAS  Google Scholar 

  • Taherali, F., Varum, F., and Basit, A.W. (2018). A slippery slope: on the origin, role and physiology of mucus. Adv Drug Deliv Rev 124, 16–33.

    Article  CAS  PubMed  Google Scholar 

  • Tan, P., Fu, H., and Ma, X. (2021). Design, optimization, and nanotechnology of antimicrobial peptides: from exploration to applications. Nano Today 39, 101229.

    Article  CAS  Google Scholar 

  • Wang, X., Cao, Z., Zhang, M., Meng, L., Ming, Z., and Liu, J. (2020). Bioinspired oral delivery of gut microbiota by self-coating with biofilms. Sci Adv 6, eabb1952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, X., Jiang, X.R., Wu, F., Ma, Y., Che, X., Chen, X., Liu, P., Zhang, W., Ma, X., and Chen, G.Q. (2019). Microbial poly-3-hydroxybutyrate (PHB) as a feed additive for fishes and piglets. Biotechnol J 14, 1900132.

    Article  CAS  Google Scholar 

  • Wei, D.X., Dao, J.W., and Chen, G.Q. (2018). A micro-ark for cells: highly open porous polyhydroxyalkanoate microspheres as injectable scaffolds for tissue regeneration. Adv Mater 30, 1802273.

    Article  Google Scholar 

  • Xu, P., Xi, Y., Zhu, J., Zhang, M., Luka, Z., Stolz, D.B., Cai, X., Xie, Y., Xu, M., Ren, S., et al. (2021). Intestinal sulfation is essential to protect against colitis and colonic carcinogenesis. Gastroenterology 161, 271–286.e11.

    Article  CAS  PubMed  Google Scholar 

  • Yan, J., and Bassler, B.L. (2019). Surviving as a community: antibiotic tolerance and persistence in bacterial biofilms. Cell Host Microbe 26, 15–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan, X., Liu, X.Y., Zhang, D., Zhang, Y.D., Li, Z.H., Liu, X., Wu, F., and Chen, G.Q. (2021). Construction of a sustainable 3-hydroxybutyrate-producing probiotic Escherichia coli for treatment of colitis. Cell Mol Immunol 18, 2344–2357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, K., Fan, K.H., Newmark, H., Leung, D., Lipkin, M., Steele, V.E., and Kelloff, G.J. (1996). Cytokeratin, lectin, and acidic mucin modulation in differentiating colonic epithelial cells of mice after feeding western-style diets. Cancer Res 56, 4644–4648.

    CAS  PubMed  Google Scholar 

  • Yang, Q., Bermingham, N.A., Finegold, M.J., and Zoghbi, H.Y. (2001). Requirement of Math1 for secretory cell lineage commitment in the mouse intestine. Science 294, 2155–2158.

    Article  CAS  PubMed  Google Scholar 

  • Zmora, N., Zilberman-Schapira, G., Suez, J., Mor, U., Dori-Bachash, M., Bashiardes, S., Kotler, E., Zur, M., Regev-Lehavi, D., Brik, R.B.Z., et al. (2018). Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell 174, 1388–1405.e21.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Key Research and Development Program of China (2022YFD1300400), the National Natural Science Foundation of China (31930106 and 31829004), the Chinese Universities Scientific Fund (2022TC033), the 2115 Talent Development Program of China Agricultural University (1041-00109019), the Henan Province Public Benefit Research Foundation (201300111200-05), and the 111 Project (B16044).

Author information

Author notes

  1. Contributed equally to this work

Authors and Affiliations

  1. State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China

    Ning Ma, Pingting Guo, Zengkai Qi, Chunchen Liu, Jiakun Shen, Yiwei Sun, Xiyue Chen & Xi Ma

  2. Beijing Laboratory for Food Quality and Safety, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China

    Jingyu Chen

  3. Center for Synthetic and Systems Biology, MOE Key Lab for Industrial Biocatalysis, School of Life Sciences and Dept Chemical Engineering, Tsinghua University, Beijing, 100084, China

    Guo-Qiang Chen

Authors
  1. Ning Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pingting Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jingyu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zengkai Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chunchen Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiakun Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yiwei Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiyue Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Guo-Qiang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Xi Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Guo-Qiang Chen or Xi Ma.

Additional information

Compliance and ethics

The author(s) declare that they have no conflict of interest.

Electronic supplementary material

11427_2022_2213_MOESM1_ESM.docx

Supporting Information: Poly-β-hydroxybutyrate alleviated diarrhea and colitis via Lactobacillus johnsonii biofilm-mediated maturation of sulfomucin

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ma, N., Guo, P., Chen, J. et al. Poly-β-hydroxybutyrate alleviated diarrhea and colitis via Lactobacillus johnsonii biofilm-mediated maturation of sulfomucin. Sci. China Life Sci. 66, 1569–1588 (2023). https://doi.org/10.1007/s11427-022-2213-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-022-2213-6

Keywords

Search

Navigation