Could the Spike Protein Derived from mRNA Vaccines Negatively Impact Beneficial Bacteria in the Gut?
Abstract
:1. Correlation between COVID-19 Disease and GM
2. Correlation between Vaccination Status and GM
3. The Hypothesis
4. Proposed In Vitro Analysis
4.1. Cell Culture
- Use human intestinal epithelial cells (e.g., Caco-2 cells).
- Grow cells in Dulbecco’s modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum and antibiotics at 37 °C with 5% CO2.
4.2. Treatment with Synthetic Spike Protein
- Divide cells into three groups: control (no treatment), low-dose spike protein (e.g., 10 ng/mL), and high-dose spike protein (e.g., 100 ng/mL).
- Treat cells for 24, 48, and 72 h.
4.3. Cytokine Analysis
- Collect cell culture supernatants at each time point.
- Measure cytokine levels (e.g., IL-6, IL-8, TNF-α) using ELISA kits.
4.4. Tight Junction Protein Expression
- Harvest cells at each time point.
- Analyze the expression of tight junction proteins (e.g., occludin, claudin 1, ZO-1) by Western blotting and immunofluorescence.
4.5. Cell Viability Assay
- Perform an MTT assay to assess cell viability after treatment.
5. Potential In Vivo Study
5.1. Animal Model
- Use C57BL/6 mice, 8–10 weeks old.
- Divide mice into three groups: control (saline), low-dose spike protein (e.g., 10 μg/kg), and high-dose spike protein (e.g., 100 μg/kg).
5.2. Administration of Synthetic Spike Protein
- Administer synthetic spike protein via intramuscular injection.
5.3. Inflammatory Response
- Collect blood samples on days 0, 7, and 14.
- Measure serum cytokine levels (e.g., IL-6, IL-8, TNF-α) using ELISA kits.
5.4. Intestinal Tissue Analysis
- Euthanize mice on day 14.
- Collect intestinal tissues for histological analysis (H&E staining) and immunohistochemistry for tight-junction proteins.
5.5. Microbiome Analysis
- Collect fecal samples on days 0, 7, and 14.
- Perform 16S rRNA sequencing to analyze microbiome composition.
- Compare the relative abundance of beneficial and harmful bacteria between groups.
6. Discussion
- (1)
- The GM affects digestion, metabolism, immunological response, and even neurological functions. It is essential for preserving general health [57,58]. This delicate ecosystem might be altered if the spike protein or its components were discovered to interact with and damage beneficial commensal bacteria in the gut.
- (2)
- Proper development and control of the immune system depend on gut microbes. Dysbiosis, or changes in the GM composition, has been connected to several immune-related diseases and disorders [59]. Investigating the potential effects of the spike protein on the GM could provide insight into possible immune dysregulation mechanisms.
- (3)
- The ACE2 receptor is the primary route via which SARS-CoV-2 infects human cells [60]; however, the spike protein may also interact with other receptors or parts of the cell, such as those found on the surface of bacteria [61]. Studying these interactions is intriguing from a scientific standpoint because it may shed light on hitherto undiscovered aspects of viral biology and host-virus dynamics.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Quigley, E.M. Gut bacteria in health and disease. Gastroenterol. Hepatol. 2013, 9, 560. [Google Scholar]
- Mills, S.; Stanton, C.; Lane, J.A.; Smith, G.J.; Ross, R.P. Precision nutrition and the microbiome, part I: Current state of the science. Nutrients 2019, 11, 923. [Google Scholar] [CrossRef]
- Rothschild, D.; Weissbrod, O.; Barkan, E.; Kurilshikov, A.; Korem, T.; Zeevi, D.; Costea, P.I.; Godneva, A.; Kalka, I.N.; Bar, N. Environment dominates over host genetics in shaping human gut microbiota. Nature 2018, 555, 210–215. [Google Scholar] [CrossRef]
- Wiley, N.; Dinan, T.; Ross, R.; Stanton, C.; Clarke, G.; Cryan, J. The microbiota-gut-brain axis as a key regulator of neural function and the stress response: Implications for human and animal health. J. Anim. Sci. 2017, 95, 3225–3246. [Google Scholar] [PubMed]
- Zheng, P.; Zeng, B.; Liu, M.; Chen, J.; Pan, J.; Han, Y.; Liu, Y.; Cheng, K.; Zhou, C.; Wang, H. The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice. Sci. Adv. 2019, 5, eaau8317. [Google Scholar] [CrossRef] [PubMed]
- Geuking, M.B.; Köller, Y.; Rupp, S.; McCoy, K.D. The interplay between the gut microbiota and the immune system. Gut Microbes 2014, 5, 411–418. [Google Scholar] [CrossRef]
- Burgueno, J.F.; Reich, A.; Hazime, H.; Quintero, M.A.; Fernandez, I.; Fritsch, J.; Santander, A.M.; Brito, N.; Damas, O.M.; Deshpande, A. Expression of SARS-CoV-2 entry molecules ACE2 and TMPRSS2 in the gut of patients with IBD. Inflamm. Bowel Dis. 2020, 26, 797–808. [Google Scholar] [CrossRef]
- Chen, Y.; Chen, L.; Deng, Q.; Zhang, G.; Wu, K.; Ni, L.; Yang, Y.; Liu, B.; Wang, W.; Wei, C. The presence of SARS-CoV-2 RNA in the feces of COVID-19 patients. J. Med. Virol. 2020, 92, 833–840. [Google Scholar] [CrossRef] [PubMed]
- Wölfel, R.; Corman, V.M.; Guggemos, W.; Seilmaier, M.; Zange, S.; Müller, M.A.; Niemeyer, D.; Jones, T.C.; Vollmar, P.; Rothe, C. Virological assessment of hospitalized patients with COVID-2019. Nature 2020, 581, 465–469. [Google Scholar] [CrossRef]
- Zhou, Z.; Zhao, N.; Shu, Y.; Han, S.; Chen, B.; Shu, X. Effect of gastrointestinal symptoms in patients with COVID-19. Gastroenterology 2020, 158, 2294–2297. [Google Scholar] [CrossRef]
- Zuo, T.; Zhang, F.; Lui, G.C.; Yeoh, Y.K.; Li, A.Y.; Zhan, H.; Wan, Y.; Chung, A.C.; Cheung, C.P.; Chen, N. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology 2020, 159, 944–955.e948. [Google Scholar] [CrossRef] [PubMed]
- Yeoh, Y.K.; Zuo, T.; Lui, G.C.-Y.; Zhang, F.; Liu, Q.; Li, A.Y.; Chung, A.C.; Cheung, C.P.; Tso, E.Y.; Fung, K.S. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut 2021, 70, 698–706. [Google Scholar] [CrossRef]
- Tay, M.Z.; Poh, C.M.; Rénia, L.; MacAry, P.A.; Ng, L.F. The trinity of COVID-19: Immunity, inflammation and intervention. Nat. Rev. Immunol. 2020, 20, 363–374. [Google Scholar] [CrossRef]
- Liu, Y.; Chan, M.T.; Chan, F.K.; Wu, W.K.; Ng, S.C.; Zhang, L. Lower gut abundance of Eubacterium rectale is linked to COVID-19 mortality. Front. Cell. Infect. Microbiol. 2023, 13, 1249069. [Google Scholar] [CrossRef]
- Rueca, M.; Fontana, A.; Bartolini, B.; Piselli, P.; Mazzarelli, A.; Copetti, M.; Binda, E.; Perri, F.; Gruber, C.E.M.; Nicastri, E. Investigation of nasal/oropharyngeal microbial community of COVID-19 patients by 16S rDNA sequencing. Int. J. Environ. Res. Public Health 2021, 18, 2174. [Google Scholar] [CrossRef] [PubMed]
- Trøseid, M.; Holter, J.C.; Holm, K.; Vestad, B.; Sazonova, T.; Granerud, B.K.; Dyrhol-Riise, A.M.; Holten, A.R.; Tonby, K.; Kildal, A.B. Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19. Crit. Care 2023, 27, 69. [Google Scholar] [CrossRef]
- Brogna, C.; Brogna, B.; Bisaccia, D.R.; Lauritano, F.; Marino, G.; Montano, L.; Cristoni, S.; Prisco, M.; Piscopo, M. Could SARS-CoV-2 have bacteriophage behavior or induce the activity of other bacteriophages? Vaccines 2022, 10, 708. [Google Scholar] [CrossRef]
- Brogna, C.; Cristoni, S.; Petrillo, M.; Bisaccia, D.R.; Lauritano, F.; Montano, L.; Prisco, M.; Piscopo, M. The first report on detecting SARS-CoV-2 inside bacteria of the human gut microbiome: A case series on asymptomatic family members and a child with COVID-19. F1000Research 2022, 11, 135. [Google Scholar] [CrossRef]
- Brogna, C.; Costanzo, V.; Brogna, B.; Bisaccia, D.R.; Brogna, G.; Giuliano, M.; Montano, L.; Viduto, V.; Cristoni, S.; Fabrowski, M. Analysis of bacteriophage behavior of a human RNA virus, SARS-CoV-2, through the integrated approach of immunofluorescence microscopy, proteomics and D-amino acid quantification. Int. J. Mol. Sci. 2023, 24, 3929. [Google Scholar] [CrossRef]
- Petrillo, M.; Querci, M.; Brogna, C.; Ponti, J.; Cristoni, S.; Markov, P.V.; Valsesia, A.; Leoni, G.; Benedetti, A.; Wiss, T. Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota. F1000Research 2022, 11, 292. [Google Scholar] [CrossRef]
- Suskun, C.; Kilic, O.; Yilmaz Ciftdogan, D.; Guven, S.; Karbuz, A.; Ozkaya Parlakay, A.; Kara, Y.; Kacmaz, E.; Sahin, A.; Boga, A. Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C). Eur. J. Pediatr. 2022, 181, 3175–3191. [Google Scholar] [CrossRef]
- Lesgards, J.-F.; Cerdan, D.; Perronne, C.; Sabatier, J.-M.; Azalbert, X.; Rodgers, E.A.; McCullough, P.A. Toxicity of SARS-CoV-2 Spike Protein from the Virus and Produced from COVID-19 mRNA or Adenoviral DNA Vaccines. Microbiol. Immunol. 2023, 7, 121–138. [Google Scholar] [CrossRef]
- Parry, P.I.; Lefringhausen, A.; Turni, C.; Neil, C.J.; Cosford, R.; Hudson, N.J.; Gillespie, J. ‘Spikeopathy’: COVID-19 spike protein is pathogenic, from both virus and vaccine mRNA. Biomedicines 2023, 11, 2287. [Google Scholar] [CrossRef]
- Cosentino, M.; Marino, F. Understanding the pharmacology of COVID-19 mRNA vaccines: Playing dice with the spike? Int. J. Mol. Sci. 2022, 23, 10881. [Google Scholar] [CrossRef]
- Ksiazek, T.G.; Erdman, D.; Goldsmith, C.S.; Zaki, S.R.; Peret, T.; Emery, S.; Tong, S.; Urbani, C.; Comer, J.A.; Lim, W. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 2003, 348, 1953–1966. [Google Scholar] [CrossRef] [PubMed]
- Peiris, J.S.M.; Chu, C.-M.; Cheng, V.C.-C.; Chan, K.; Hung, I.; Poon, L.L.; Law, K.-I.; Tang, B.; Hon, T.; Chan, C. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: A prospective study. Lancet 2003, 361, 1767–1772. [Google Scholar] [CrossRef]
- Kurt-Jones, E.A.; Dudek, T.E.; Watanabe, D.; Mandell, L.; Che, J.; Zhou, S.; Cao, L.; Greenough, T.; Babcock, G.J.; Diaz, F. Expression of SARS coronavirus 1 spike protein from a herpesviral vector induces innate immune signaling and neutralizing antibody responses. Virology 2021, 559, 165–172. [Google Scholar] [CrossRef]
- Trypsteen, W.; Van Cleemput, J.; Snippenberg, W.v.; Gerlo, S.; Vandekerckhove, L. On the whereabouts of SARS-CoV-2 in the human body: A systematic review. PLoS Pathog. 2020, 16, e1009037. [Google Scholar] [CrossRef] [PubMed]
- Argenziano, M.G.; Bruce, S.L.; Slater, C.L.; Tiao, J.R.; Baldwin, M.R.; Barr, R.G.; Chang, B.P.; Chau, K.H.; Choi, J.J.; Gavin, N. Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: Retrospective case series. BMJ 2020, 369, m1996. [Google Scholar] [CrossRef]
- Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506. [Google Scholar] [CrossRef]
- Lin, L.; Jiang, X.; Zhang, Z.; Huang, S.; Zhang, Z.; Fang, Z.; Gu, Z.; Gao, L.; Shi, H.; Mai, L. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut 2020, 69, 997–1001. [Google Scholar] [CrossRef] [PubMed]
- Chu, K.H.; Tsang, W.K.; Tang, C.S.; Lam, M.F.; Lai, F.M.; To, K.F.; Fung, K.S.; Tang, H.L.; Yan, W.W.; Chan, H.W. Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Kidney Int. 2005, 67, 698–705. [Google Scholar] [CrossRef] [PubMed]
- Mao, L.; Jin, H.; Wang, M.; Hu, Y.; Chen, S.; He, Q.; Chang, J.; Hong, C.; Zhou, Y.; Wang, D. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020, 77, 683–690. [Google Scholar] [CrossRef]
- Castruita, J.A.S.; Schneider, U.V.; Mollerup, S.; Leineweber, T.D.; Weis, N.; Bukh, J.; Pedersen, M.S.; Westh, H. SARS-CoV-2 spike mRNA vaccine sequences circulate in blood up to 28 days after COVID-19 vaccination. Apmis 2023, 131, 128–132. [Google Scholar] [CrossRef] [PubMed]
- Bansal, S.; Perincheri, S.; Fleming, T.; Poulson, C.; Tiffany, B.; Bremner, R.M.; Mohanakumar, T. Cutting edge: Circulating exosomes with COVID spike protein are induced by BNT162b2 (Pfizer–BioNTech) vaccination prior to development of antibodies: A novel mechanism for immune activation by mRNA vaccines. J. Immunol. 2021, 207, 2405–2410. [Google Scholar] [CrossRef] [PubMed]
- Brogna, C.; Cristoni, S.; Marino, G.; Montano, L.; Viduto, V.; Fabrowski, M.; Lettieri, G.; Piscopo, M. Detection of recombinant Spike protein in the blood of individuals vaccinated against SARS-CoV-2: Possible molecular mechanisms. PROTEOMICS–Clin. Appl. 2023, 17, 2300048. [Google Scholar] [CrossRef]
- Broudic, K.; Laurent, S.; Perkov, V.; Simon, C.; Garinot, M.; Truchot, N.; Latour, J.; Désert, P. Nonclinical safety assessment of an mRNA Covid-19 vaccine candidate following repeated administrations and biodistribution. J. Appl. Toxicol. 2024, 44, 371–390. [Google Scholar] [CrossRef]
- Hassett, K.J.; Benenato, K.E.; Jacquinet, E.; Lee, A.; Woods, A.; Yuzhakov, O.; Himansu, S.; Deterling, J.; Geilich, B.M.; Ketova, T. Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Mol. Ther.-Nucleic Acids 2019, 15, 1–11. [Google Scholar] [CrossRef]
- Reichmuth, A.M.; Oberli, M.A.; Jaklenec, A.; Langer, R.; Blankschtein, D. mRNA vaccine delivery using lipid nanoparticles. Ther. Deliv. 2016, 7, 319–334. [Google Scholar] [CrossRef]
- Röltgen, K.; Nielsen, S.C.; Silva, O.; Younes, S.F.; Zaslavsky, M.; Costales, C.; Yang, F.; Wirz, O.F.; Solis, D.; Hoh, R.A. Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination. Cell 2022, 185, 1025–1040.e1014. [Google Scholar] [CrossRef]
- Lindsay, K.E.; Bhosle, S.M.; Zurla, C.; Beyersdorf, J.; Rogers, K.A.; Vanover, D.; Xiao, P.; Araínga, M.; Shirreff, L.M.; Pitard, B. Visualization of early events in mRNA vaccine delivery in non-human primates via PET–CT and near-infrared imaging. Nat. Biomed. Eng. 2019, 3, 371–380. [Google Scholar] [CrossRef] [PubMed]
- Krauson, A.J.; Casimero, F.V.C.; Siddiquee, Z.; Stone, J.R. Duration of SARS-CoV-2 mRNA vaccine persistence and factors associated with cardiac involvement in recently vaccinated patients. npj Vaccines 2023, 8, 141. [Google Scholar] [CrossRef]
- Angeli, F.; Spanevello, A.; Reboldi, G.; Visca, D.; Verdecchia, P. SARS-CoV-2 vaccines: Lights and shadows. Eur. J. Intern. Med. 2021, 88, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Zhang, S.; Liu, Y.; Wang, X.; Yang, L.; Li, H.; Wang, Y.; Liu, M.; Zhao, X.; Xie, Y.; Yang, Y. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J. Hematol. Oncol. 2020, 13, 120. [Google Scholar] [CrossRef] [PubMed]
- Seneff, S.; Kyriakopoulos, A.M.; Nigh, G.; McCullough, P.A. A potential role of the spike protein in neurodegenerative diseases: A narrative review. Cureus 2023, 15, e34872. [Google Scholar] [CrossRef]
- Hazan, S.; Stollman, N.; Bozkurt, H.S.; Dave, S.; Papoutsis, A.J.; Daniels, J.; Barrows, B.D.; Quigley, E.M.; Borody, T.J. Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity. BMJ Open Gastroenterol. 2022, 9, e000871. [Google Scholar] [CrossRef]
- Hazan, S.; Dave, S.; Barrows, B.; Borody, T.J. S227 Messenger RNA SARS-CoV-2 Vaccines Affect the Gut Microbiome. Off. J. Am. Coll. Gastroenterol. | ACG 2022, 117, e162. [Google Scholar] [CrossRef]
- Hikmet, F.; Méar, L.; Edvinsson, Å.; Micke, P.; Uhlén, M.; Lindskog, C. The protein expression profile of ACE2 in human tissues. Mol. Syst. Biol. 2020, 16, e9610. [Google Scholar] [CrossRef]
- Yonker, L.M.; Gilboa, T.; Ogata, A.F.; Senussi, Y.; Lazarovits, R.; Boribong, B.P.; Bartsch, Y.C.; Loiselle, M.; Rivas, M.N.; Porritt, R.A.; et al. Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier. J. Clin. Investig. 2021, 131, e149633. [Google Scholar] [CrossRef] [PubMed]
- Camargo, S.M.; Singer, D.; Makrides, V.; Huggel, K.; Pos, K.M.; Wagner, C.A.; Kuba, K.; Danilczyk, U.; Skovby, F.; Kleta, R. Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. Gastroenterology 2009, 136, 872–882.e873. [Google Scholar] [CrossRef]
- Stevens, B.R.; Ellory, J.C.; Preston, R.L. B0AT1 amino acid transporter complexed with SARS-CoV-2 receptor ACE2 forms a heterodimer functional unit: In situ conformation using radiation inactivation analysis. Function 2021, 2, zqab027. [Google Scholar] [CrossRef] [PubMed]
- Hashimoto, T.; Perlot, T.; Rehman, A.; Trichereau, J.; Ishiguro, H.; Paolino, M.; Sigl, V.; Hanada, T.; Hanada, R.; Lipinski, S. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 2012, 487, 477–481. [Google Scholar] [CrossRef]
- Cosola, C.; Rocchetti, M.T.; Gesualdo, L. Gut microbiota, the immune system, and cytotoxic T lymphocytes. Cytotoxic T-Cells: Methods Protoc. 2021, 2325, 229–241. [Google Scholar]
- Chen, H.; Wang, J.; Ding, K.; Xu, J.; Yang, Y.; Tang, C.; Zhou, Y.; Yu, W.; Wang, H.; Huang, Q. Gastrointestinal microbiota and metabolites possibly contribute to distinct pathogenicity of SARS-CoV-2 proto or its variants in rhesus monkeys. Gut Microbes 2024, 16, 2334970. [Google Scholar] [CrossRef] [PubMed]
- Brogna, C.; Viduto, V.; Fabrowski, M.; Cristoni, S.; Marino, G.; Montano, L.; Piscopo, M. The importance of the gut microbiome in the pathogenesis and transmission of SARS-CoV-2: Someone on Earth:“… we moved at the speed of Science!”-Science from the center of the Universe:“Hey man, I’m still waiting for you in the 50s!”. Gut Microbes 2023, 15, 2244718. [Google Scholar] [CrossRef] [PubMed]
- Hazan, S.; Dave, S.; Barrows, B.; Borody, T.J. S2099 Persistent Damage to the Gut Microbiome Following Messenger RNA SARS-CoV-2 Vaccine. Off. J. Am. Coll. Gastroenterol. | ACG 2022, 117, e1429–e1430. [Google Scholar] [CrossRef]
- Al Bander, Z.; Nitert, M.D.; Mousa, A.; Naderpoor, N. The gut microbiota and inflammation: An overview. Int. J. Environ. Res. Public Health 2020, 17, 7618. [Google Scholar] [CrossRef]
- Laudes, M.; Geisler, C.; Rohmann, N.; Bouwman, J.; Pischon, T.; Schlicht, K. Microbiota in health and disease—Potential clinical applications. Nutrients 2021, 13, 3866. [Google Scholar] [CrossRef]
- Campbell, C.; Kandalgaonkar, M.R.; Golonka, R.M.; Yeoh, B.S.; Vijay-Kumar, M.; Saha, P. Crosstalk between gut microbiota and host immunity: Impact on inflammation and immunotherapy. Biomedicines 2023, 11, 294. [Google Scholar] [CrossRef]
- Scialo, F.; Daniele, A.; Amato, F.; Pastore, L.; Matera, M.G.; Cazzola, M.; Castaldo, G.; Bianco, A. ACE2: The major cell entry receptor for SARS-CoV-2. Lung 2020, 198, 867–877. [Google Scholar] [CrossRef]
- Fazel, P.; Sedighian, H.; Behzadi, E.; Kachuei, R.; Imani Fooladi, A.A. Interaction between SARS-coV-2 and pathogenic bacteria. Curr. Microbiol. 2023, 80, 223. [Google Scholar] [CrossRef] [PubMed]
- Jiao, J.; Shen, Y.; Wang, P.; Zuo, K.; Yang, X.; Chen, M.; Dong, Y.; Li, J. Characterization of the intestinal microbiome in healthy adults over Sars-Cov-2 vaccination. Front. Biosci.-Landmark 2022, 27, 280. [Google Scholar] [CrossRef]
- Singer, J.; Tunbridge, M.; Perkins, G.B.; Salehi, T.; Ying, T.; Wu, H.; Coates, P.T.; Chadban, S.J. Rapamycin and inulin for third-dose vaccine response stimulation (RIVASTIM): Inulin–study protocol for a pilot, multicentre, randomised, double-blinded, controlled trial of dietary inulin to improve SARS-CoV-2 vaccine response in kidney transplant recipients. BMJ Open 2022, 12, e062747. [Google Scholar]
- Shen, Y.; Dong, Y.; Jiao, J.; Wang, P.; Chen, M.; Li, J. BBIBP-corV vaccination against the SARS-coV-2 virus affects the gut microbiome. Vaccines 2023, 11, 942. [Google Scholar] [CrossRef]
- Lynn, D.J.; Benson, S.C.; Lynn, M.A.; Pulendran, B. Modulation of immune responses to vaccination by the microbiota: Implications and potential mechanisms. Nat. Rev. Immunol. 2022, 22, 33–46. [Google Scholar] [CrossRef]
- Hagan, T.; Cortese, M.; Rouphael, N.; Boudreau, C.; Linde, C.; Maddur, M.S.; Das, J.; Wang, H.; Guthmiller, J.; Zheng, N.-Y. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell 2019, 178, 1313–1328.e1313. [Google Scholar] [CrossRef]
- de Jong, S.E.; Olin, A.; Pulendran, B. The impact of the microbiome on immunity to vaccination in humans. Cell Host Microbe 2020, 28, 169–179. [Google Scholar] [CrossRef] [PubMed]
- Hong, M.; Lan, T.; Li, Q.; Li, B.; Yuan, Y.; Xu, F.; Wang, W. A comprehensive perspective on the interaction between gut microbiota and COVID-19 vaccines. Gut Microbes 2023, 15, 2233146. [Google Scholar] [CrossRef] [PubMed]
- Stojanov, S.; Berlec, A.; Štrukelj, B. The influence of probiotics on the firmicutes/bacteroidetes ratio in the treatment of obesity and inflammatory bowel disease. Microorganisms 2020, 8, 1715. [Google Scholar] [CrossRef]
- Dillon, S.; Lee, E.; Kotter, C.; Austin, G.; Dong, Z.; Hecht, D.; Gianella, S.; Siewe, B.; Smith, D.; Landay, A. An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia. Mucosal Immunol. 2014, 7, 983–994. [Google Scholar] [CrossRef]
- Vázquez-Castellanos, J.; Serrano-Villar, S.; Latorre, A.; Artacho, A.; Ferrús, M.; Madrid, N.; Vallejo, A.; Sainz, T.; Martínez-Botas, J.; Ferrando-Martínez, S. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals. Mucosal Immunol. 2015, 8, 760–772. [Google Scholar] [CrossRef]
- Devi, T.B.; Devadas, K.; George, M.; Gandhimathi, A.; Chouhan, D.; Retnakumar, R.; Alexander, S.M.; Varghese, J.; Dharmaseelan, S.; Chandrika, S.K. Low Bifidobacterium abundance in the lower gut microbiota is associated with Helicobacter pylori-related gastric ulcer and gastric cancer. Front. Microbiol. 2021, 12, 631140. [Google Scholar] [CrossRef] [PubMed]
- Hibberd, A.A.; Lyra, A.; Ouwehand, A.C.; Rolny, P.; Lindegren, H.; Cedgård, L.; Wettergren, Y. Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention. BMJ Open Gastroenterol. 2017, 4, e000145. [Google Scholar] [CrossRef]
- Kosumi, K.; Hamada, T.; Koh, H.; Borowsky, J.; Bullman, S.; Twombly, T.S.; Nevo, D.; Masugi, Y.; Liu, L.; da Silva, A. The amount of Bifidobacterium genus in colorectal carcinoma tissue in relation to tumor characteristics and clinical outcome. Am. J. Pathol. 2018, 188, 2839–2852. [Google Scholar] [CrossRef]
- Li, J.; Chu, R.; Wang, C.; Li, Y.; Wu, B.; Wan, J. Microbiome characteristics and Bifidobacterium longum in colorectal cancer patients pre-and post-chemotherapy. Transl. Cancer Res. 2020, 9, 2178. [Google Scholar] [CrossRef] [PubMed]
- Elahi, Z.; Shariati, A.; Bostanghadiri, N.; Dadgar-Zankbar, L.; Razavi, S.; Norzaee, S.; Arasi, S.V.; Darban-Sarokhalil, D. Association of Lactobacillus, Firmicutes, Bifidobacterium, Clostridium, and Enterococcus with colorectal cancer in Iranian patients. Heliyon 2023, 9, e22602. [Google Scholar] [CrossRef]
- Huck, M.B.; Bohl, J.L. Colonic polyps: Diagnosis and surveillance. Clin. Colon Rectal Surg. 2016, 29, 296–305. [Google Scholar] [CrossRef]
- Vogelstein, B.; Fearon, E.R.; Hamilton, S.R.; Kern, S.E.; Preisinger, A.C.; Leppert, M.; Smits, A.M.; Bos, J.L. Genetic alterations during colorectal-tumor development. N. Engl. J. Med. 1988, 319, 525–532. [Google Scholar] [CrossRef]
- Fearon, E.R.; Vogelstein, B. A genetic model for colorectal tumorigenesis. cell 1990, 61, 759–767. [Google Scholar] [CrossRef]
- Morson, B. The evolution of colorectal carcinoma. Clin. Radiol. 1984, 35, 425–431. [Google Scholar] [CrossRef]
- Atkin, W.S.; Morson, B.C.; Cuzick, J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N. Engl. J. Med. 1992, 326, 658–662. [Google Scholar] [CrossRef]
- Dalile, B.; Van Oudenhove, L.; Vervliet, B.; Verbeke, K. The role of short-chain fatty acids in microbiota–gut–brain communication. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 461–478. [Google Scholar] [CrossRef] [PubMed]
- Iida, N.; Dzutsev, A.; Stewart, C.A.; Smith, L.; Bouladoux, N.; Weingarten, R.A.; Molina, D.A.; Salcedo, R.; Back, T.; Cramer, S. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 2013, 342, 967–970. [Google Scholar] [CrossRef] [PubMed]
- Vétizou, M.; Pitt, J.M.; Daillère, R.; Lepage, P.; Waldschmitt, N.; Flament, C.; Rusakiewicz, S.; Routy, B.; Roberti, M.P.; Duong, C.P. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015, 350, 1079–1084. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Rubio-Casillas, A.; Fabrowski, M.; Brogna, C.; Cowley, D.; Redwan, E.M.; Uversky, V.N. Could the Spike Protein Derived from mRNA Vaccines Negatively Impact Beneficial Bacteria in the Gut? COVID 2024, 4, 1368-1378. https://doi.org/10.3390/covid4090097
Rubio-Casillas A, Fabrowski M, Brogna C, Cowley D, Redwan EM, Uversky VN. Could the Spike Protein Derived from mRNA Vaccines Negatively Impact Beneficial Bacteria in the Gut? COVID. 2024; 4(9):1368-1378. https://doi.org/10.3390/covid4090097
Chicago/Turabian StyleRubio-Casillas, Alberto, Mark Fabrowski, Carlo Brogna, David Cowley, Elrashdy M. Redwan, and Vladimir N. Uversky. 2024. "Could the Spike Protein Derived from mRNA Vaccines Negatively Impact Beneficial Bacteria in the Gut?" COVID 4, no. 9: 1368-1378. https://doi.org/10.3390/covid4090097