The document discusses the interplay between gut microbiota and immunity, highlighting its impact on various health conditions, including diseases like COVID-19 and cancer. It emphasizes the potential of microbiome modulation through prebiotics and probiotics to influence immune responses and improve health outcomes. Furthermore, it identifies ongoing research into the clinical application of microbiome manipulation as a strategy for treating and preventing immune-mediated diseases.

1. Microbiata
A main player in immunity

4. Intestinal microbiota-immunity
interplay in homeostasis.
Cell Research volume 30, pages492–506 (2020)

5. Microbiome-immunity interaction in extra-intestinal organs
Cell Research volume 30, pages492–506 (2020)

6. the activation of immune cells by probiotics
does not alter intestinal homeostasis, probably
by the regulatory cells activation that
maintains a tolerogenic environment.
These facts ensure the safety of probiotics
consumption for long periods of time without
adverse effects
Ann Nutr Metab 2019;74:115–124

8. Intercommunication between the host and the gut microbiome

11. Front. Cell. Neurosci., 06 July 2021 | https://doi.org/10.3389/fncel.2021.698126
Age-associated alterations in the brain innate immunity and the gut microbiota

12. Dysregulation of microbiome-immunity interaction in disease.
Cell Research volume 30, pages492–506 (2020)

13. Impact of prebiotics on immune response:the direct action of
prebiotics on immune cel
Immunology & Cell Biology, Volume: 99, Issue: 3, Pages: 255-273, First published: 30 September 2020, DOI: (10.1111/imcb.12409)

14. Immunology & Cell Biology, Volume: 99, Issue: 3, Pages: 255-273, First published: 30 September 2020, DOI: (10.1111/imcb.12409)
Direct and indirect effect of prebiotics on
gut‐associated lymphoid tissue

15. Immunology & Cell Biology, Volume: 99, Issue: 3, Pages: 255-273, First published: 30 September 2020, DOI: (10.1111/imcb.12409)
Effect of prebiotics on the innate immune response

16. Overview of clinical studies on the effect of prebiotics on innate immune cells
Immunology & Cell Biology, Volume: 99, Issue: 3, Pages: 255-273, First published: 30 September 2020, DOI: (10.1111/imcb.12409)

17. https://link.springer.com/chapter/10.1007/978-3-319-23213-3_5
Immunomodulatory actions of probiotics

18. https://link.springer.com/chapter/10.1007/978-3-319-23213-3_5
Probable immunological actions of probiotics to reduce the risk factors that
contribute to type 2 diabetes mellitus and cardiovascular diseases

19. Front. Microbiol., 21 June 2021 | https://doi.org/10.3389/fmicb.2021.688137
Impact of Probiotic Bacteria on Respiratory Allergy Disorders

20. Immune mechanisms mediated by oral probiotic administration to
control allergy at bronchial level.
Ann Nutr Metab 2019;74:115–124

21. Adv Nutr, Volume 10, Issue suppl_1, January 2019, Pages S49–S66, https://doi.org/10.1093/advances/nmy063
Main effects of probiotics on the immune system. ASC, apoptosis-associated
Speck-like protein containing a ...

23. The microbiome is an environmental factor in
intricate symbiotic relationship with its hosts'
immune system, potentially shaping:
anticancer immunity,
autoimmunity, and
transplant responses.
.
•. 2021 Aug;40(8):745-753. doi: 10.1016/j.healun.2021.04.004

24. Microbiata in organ
transplantation immunity

25. •The microbiota changes dynamically following transplantation, but
whether these changes affect transplant outcomes can be difficult to
parse out.
•New data reveal effects of the microbiota locally, as well as systemically,
depending on the mucosal/epithelial surface colonized, the specific
commensal communities present and the nature of microbial-derived
molecules produced.
•These complex interactions result in the microbiota potentially impacting
transplantation at different levels, including modulation of donor and/or
recipient cells, alterations in the priming and/or effector phases of the
alloimmune response, availability or metabolism of immunosuppressive
drugs, transplant fate or post-transplant complications.
•. 2021 Aug;40(8):745-753. doi: 10.1016/j.healun.2021.04.004

27. the gut microbiome holds great promise in changing our current understanding of disease
processes. However, only a collective interdisciplinary experimental, bioinformatical, and clinical
approach will ensure that the potentially profound scientific insight translates into a better
clinical outcome and personalized patient care of transplant patients
The gut microbiome in solid organ transplantation
Pediatric Transplantation. 2020;24:e13866.

28. there is a plethora of highly relevant, but yet unanswered questions:
1. the role of a low-diversity microbiome in common transplant-associated complications such
as allograft rejection remains to be clarified.
2. Microbiome-based biomarkers could facilitate the early identification of patients at risk and
potentially serve as a decision-making tool in risk stratification and treatment strategies. In
this context, selective culturing of pathobionts, detection of individual marker genes by
quantitative PCR, identification of protein biomarkers by antibody-based tests, and
assessment of (toxic) metabolic products by targeted mass spectrometry are potential
clinical implementation strategies.
3. Further, microbial biomarkers could be used as a tool towards personalized
immunosuppressive treatment: For example, the drug and drug dose could be determined
based on a patient's predisposition on drug exposure and toxicity rather than on population-
wide averages. Once microbial changes are established as a decisive factor in disease
pathophysiology, restoration, and specific modulation of the microbiome could be used both
therapeutically and preventively to alleviate adverse events.
4. Broad interventions, such as FMT or defined microbial consortia, could be applied to restore
gut microbial diversity, while more targeted interventions, such as phages, could be used to
eradicate individual bacterial pathogens.

29. Microbiata in cancer immunity

30. Recent scientific advances have greatly enhanced our understanding of the complex
link between the gut microbiome and cancer. Gut dysbiosis is an imbalance between
commensal and pathogenic bacteria and the production of microbial antigens and
metabolites. The immune system and the gut microbiome interact to maintain
homeostasis of the gut, and alterations in the microbiome composition lead to
immune dysregulation, promoting chronic inflammation and development of tumors.
Gut microorganisms and their toxic metabolites may migrate to other parts of the
body via the circulatory system, causing an imbalance in the physiological status of
the host and secretion of various neuroactive molecules through the gut-brain axis,
gut-hepatic axis, and gut-lung axis to affect inflammation and tumorigenesis in
specific organs. Thus, gut microbiota can be used as a tumor marker and may provide
new insights into the pathogenesis of malignant tumors
Gut microbiota influence tumor development and Alter interactions with
the human immune system
Journal of Experimental & Clinical Cancer
Research volume 40, Article number: 42 (2021)

31. •Dysregulation of the gut microbiota and its interaction with
the host may be important in tumorigenesis.
•First, we need to identify relevant bacteria in humans, study
their abundance and the impact of their products on cancer
progression, and elucidate their interactions with the human
immune system as well as their ultimate impact on the
mechanism of tumor occurrence and development.
•We then need to identify novel therapeutic microbial
interventions and combine them with conventional therapies
to treat tumors and other multifactorial human diseases.
Journal of Experimental & Clinical Cancer Research volume 40, Article number: 42 (2021

33. The antitumor and pro-tumor impact of the microbiota in cancer.

34. . Bacteria prominent during gut dysbiosis can secrete toxins able to interfere with host cell growth, finally predisposing the
host organism to cancer development. Schematic of the intestinal layers, from top to bottom: mucus and microbiota, gut
epithelium. Into the grey boxes are illustrated, from top to bottom, the microorganism species implicated in the pro-cancer
process, the molecules produced and the corresponding effects induced within the host. Abbreviations: ROS, Reactive
Oxygen Species; CTD, cytolethal distending toxin; IpgD, inositol phosphate phosphatase D; VirA, virulence gene A; CagA,
cytotoxin associated gene A; FadA, Fusobacterium effector adhesin A; MP Toxin, metalloproteinase toxin; AvrA, avirulence
protein A; β-gluc, β-glucuronidase.
Pro-tumoral effects of the gut microbiota
January 2019Cancers 11(1):38

35. Modulating the microbiome to improve therapeutic response in
cancer
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30952-5/fulltext

38. Microbiata in autoimmune diseases

39. Multiple links have been made between
microbiota and immune-mediated diseases
NAture RevIeWS |
MICRobIology Reviews
volume 18 | September
2020 | 521

40. NAture RevIeWS | MICRobIology Reviews volume 18 | September 2020 | 521

41. Dermatol Ther (Heidelb) (2021)
11:363–384

42. Microbiata in covid-19

43. Gut microbiota composition reflects disease severity and dysfunctional
immune responses in patients with COVID-19
What is already known on this subject?
► SARS-CoV-2 primarily infects the respiratory tract, however, pathophysiology of COVID-19 can
be attributed to aberrant immune responses in clearing the virus.
► Several lines of evidence such as replication of SARS-CoV-2 in human enterocytes, detection
of viruses in faecal samples and the altered gut microbiota composition in patients with COVID-
19 suggest involvement of the GI tract.
► COVID-19 gut microbiota surveys are limited and have not examined links between gut
microbiome and disease pathophysiology.
What are the new findings?
► Composition of the gut microbiota in patients with COVID-19 is concordant with disease
severity and magnitude of plasma concentrations of several inflammatory cytokines,
chemokines and blood markers of tissue damage.
► Patients with COVID-19 were depleted in gut bacteria with known immunomodulatory
potential, such as Faecalibacterium prausnitzii, Eubacterium rectale and several bifidobacterial
species.
► The dysbiotic gut microbiota composition in patients with COVID-19 persists after clearance
of the virus.
Yeoh YK, et al. Gut 2021;70:698–706. doi:10.1136/gutjnl-2020-323020

44. How might it impact on clinical practice in the foreseeable
future?
► These findings suggest that depletion of immunomodulatory
gut microorganisms contributes to severe COVID-19 disease.
► The dysbiotic gut microbiota that persists after disease
resolution could be a factor in developing persistent symptoms
and/or multisystem inflammation syndromes that occur in some
patients after clearing the virus.
► Bolstering of beneficial gut species depleted in COVID-19
could serve as a novel avenue to mitigate severe disease,
underscoring importance of managing patients’ gut microbiota
during and after COVID-19.
Gut microbiota composition reflects disease severity and dysfunctional
immune responses in patients with COVID-19
Yeoh YK, et al. Gut 2021;70:698–706. doi:10.1136/gutjnl-2020-323020

45. Timeline of the procedures performed in patients with CDI, which coincidentally occurred
during COVID-19 early stage infection.
Jarosław Biliński et al. Gut doi:10.1136/gutjnl-2021-325010
Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

46. Our findings provide early evidence regarding the use of
FMT in recurrent CDI in patients with COVID-19.
Furthermore, these data let us speculate that gut
microbiome manipulation may merit further exploration
as an immunomodulatory strategy in COVID-19. Based on
our experience here (and other data demonstrating gut
microbiome-immune interactions in humans10), we are
progressing to a clinical trial to assess the impact of FMT
added to standard COVID-19 treatment on the risk
reduction of disease progression (NCT04824222); this
should commence recruitment shortly
Timeline of the procedures performed in patients with CDI, which coincidentally occurred
during COVID-19 early stage infection.
Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.

47. Clinical trials of probiotics for COVID-19 (ClinicalTrials.gov, accessed on 15 May 2021).
J. Clin. Med. 2021, 10, 2903

48. Clinical trials of probiotics for COVID-19 (ClinicalTrials.gov, accessed on 15 May 2021).
J. Clin. Med. 2021, 10, 2903