Skip to main content

Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice

Abstract

Increased inflammation associated with leaky gut is a major risk factor for morbidity and mortality in older adults; however, successful preventive and therapeutic strategies against these conditions are not available. In this study, we demonstrate that a human-origin Lactobacillus paracasei D3-5 strain (D3-5), even in the non-viable form, extends life span of Caenorhabditis elegans. In addition, feeding of heat-killed D3-5 to old mice (> 79 weeks) prevents high- fat diet-induced metabolic dysfunctions, decreases leaky gut and inflammation, and improves physical and cognitive functions. D3-5 feeding significantly increases mucin production, and proportionately, the abundance of mucin-degrading bacteria Akkermansia muciniphila also increases. Mechanistically, we show that the lipoteichoic acid (LTA), a cell wall component of D3-5, enhances mucin (Muc2) expression by modulating TLR-2/p38-MAPK/NF-kB pathway, which in turn reduces age-related leaky gut and inflammation. The findings indicate that the D3-5 and its LTA can prevent/treat age-related leaky gut and inflammation.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

References

Download references

Acknowledgments

We would like to thank Sandy Sink for help in metabolic phenotyping studies, and Cynthia Zimmerman from Wake Forest Regenerative Medicine Histology Core for tissue processing and slide preparations. We are also thankful to Dr. John Parks and Dr. Martha Alexander Miller for providing valuable advices, suggestions, and departmental resources. C. elegans strains were generously provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). We are also thankful to all the participating researchers, technicians, and the staff members of the animal facilities and laboratory members for their consistent help during the study.

Funding

This work was supported by National Institutes of Health grant R01DK081842 (DAM), R01HL142930 (KK), R01HL132035 (XZ), R01AG059416, U13AG040938, R01AG052419, U24AG058556, KL2TR001421 (SBK), R01AG018915, R01AG045551, and U24AG059624 (DWK); the Pepper Older Americans for Independence Center (P30AG21332); and the Department of Defense funding W81XWH-18-1-0118, GRANT12726940/AZ180098, R01AG018915 (HY), as well as funds and services provided from the Center for Diabetes, Obesity and Metabolism, Wake Forest Baptist Medical Center, and the National Center for Advancing Translational Sciences (NCATS), the National Institutes of Health-funded Wake Forest Clinical, and Translational Science Institute (WF CTSI) through Grant Award Number UL1TR001420.

Author information

Authors and Affiliations

Authors

Contributions

SW, SA, RN, SJ, SPM, KK, XZ, and ZW performed and/or helped in various experiments conducted in this study as well as data compilations and interpretations, and writing first draft of manuscript. DAM, SBK, and DWK significantly contributed as intellects for experimental designs and data interpretations. HY conceived the project idea, supervised the study, compiled and interpreted data, and wrote the manuscript.

Corresponding author

Correspondence to Hariom Yadav.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 780 kb)

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wang, S., Ahmadi, S., Nagpal, R. et al. Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice. GeroScience 42, 333–352 (2020). https://doi.org/10.1007/s11357-019-00137-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-019-00137-4

Keywords

  • Aging
  • Cell wall
  • Cognition
  • Goblet cell
  • Inflammation
  • Leaky gut
  • Lipoteichoic acid
  • Metabolism
  • Mucin
  • Probiotics
  • Physical function