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Page 8 of 12 Procaccianti et al. Microbiome Res Rep 2023;2:24 https://dx.doi.org/10.20517/mrr.2023.23

hepatocellular carcinoma (NCT05178524), investigators used Bifidobacterium-rich BIFICO as an
intervention strategy to sustain medication in the perioperative period of hepatectomy and observed
postoperative liver functionality recovery. The first published research on this project revealed that the GM
profile influenced the rate at which liver function recovered after hepatectomy, and, again, Bifidobacterium
was a major player. In an interventional randomized clinical trial (NCT03112837), investigators evaluated
the impact of combined live capsules of Bifidobacterium, Lactobacillus and Enterococcus in patients with
nasopharyngeal carcinoma. In particular, the aim of this study was to determine whether GM modulation
reduced the severity of radiation-induced mucositis in patients receiving radical dose radiotherapy. Indeed,
radiation-induced mucositis is an acute mucosal reaction of patients undergoing head and neck
radiotherapy, which leads to dose-limiting and debilitating side effects.

CONCLUSIONS AND FUTURE TRENDS
GM has now taken a leading role in research focused on maintaining host well-being, including the success
of anticancer therapies. In this scenario, several works have linked Bifidobacterium to improved response to
immunochemotherapy. However, its well-known anti-inflammatory and immunosuppressive properties
and its recent association with platinum resistance do not allow definitive conclusions to be drawn.
Nevertheless, some clinical trials are already underway involving the intake of Bifidobacterium directly in
cancer patients. It goes without saying that further studies in large cohorts are needed to fill the many
knowledge gaps and provide robust experimental evidence. Such studies should possibly be conducted with
different omics approaches (including metabolomics) and animal models to finally go beyond simple
associations and uncover the underlying molecular mechanisms. Only the achievement of such a goal will
truly allow precision strategies to be implemented. In the near future, it is possible to foresee not only that
Bifidobacteriuml strains will be rationally used to induce certain anticancer effects in a given context, but
that they will eventually be engineered to either boost or hinder some functionalities instrumental to the
success of immunochemotherapy protocols. Not least, it is possible to envisage the use of Bifidobacterium-
derived postbiotics to specifically confer beneficial effects by directly using the molecular actors involved.
[88]
This could be particularly relevant in the case of cancer patients, often immunocompromised and with an
increased risk of infections and sepsis.

DECLARATIONS
Authors’ contributions
Wrote the original draft: Procaccianti G, Roggiani S, Conti G
Reviewed and edited the manuscript: Turroni S, D’Amico F
Supervised during the draft preparation: D’Amico F, Turroni S, Brigidi P
All authors have read and agreed to the published version of the manuscript.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.