A deep relationship between the gut microbiota and immune cells dynamics in humans
The gut microbiota has a fundamental role in modulating the activity of the immune system, its efficiency and its composition. Indeed, multiple studies highlighted the deep connection between gut microbiome composition and immunotherapies diverse outcomes. The effect of gut microbiome on the immune system homeostasis has been prevalently studied in animal models so far but the relevance of those studies could be argued based on some differences between animals and humans. The work of J. Schuler et Al. aims to fill the gap in our understanding of gut microbiome-immunity correlation in human subjects.
Researchers collected a large number of data regarding the immune-reconstitution dynamics in patients that received an allogeneic haematopoietic transplant after heavy radiotherapy or chemotherapy, in a period of time that went from 2003 to 2019. The treatments and the transplant cause a severe alteration in blood cell counts as well as a reduction in microbiota diversity. Homeostasis is heterogeneously reconstituted in each patient. The process is orchestrated by both immunomodulators, such as GCSF, and gut microbiota.
The existence of a correlation between the role of gut microbiota and WBCs counts was firstly demonstrated with auto-FMT performed at different times after neutrophils engraftment in a small cohort (24 patients). Overall, people receiving the auto-FMT showed higher counts of neutrophils, monocytes and lymphocytes compared to other patients. This result is probably related to the anticipated restoration of a complete and heterogeneous gut microbiome thanks to FMT that supports WBCs levels recovery and a better clinical outcome.
The following large scale observational study was organized in two stages. The first one had the aim to analyse the daily WBCs and find a correlation between day-to-day variation and the kind of medication received. In the second stage the purpose was to integrate the information collected previously and describe the contribution of the gut microbiome in the observed restoration dynamics.
Apart from confirming the already known activity of classical medications on WBCs counts, some interesting associations between microbial species abundance and WBCs dynamics were highlighted. Data showed a positive correlation between Faecalibacterium, Ruminococcus and Akkermansia presence and neutrophils rates and between Ruminococcus 2 and Staphylococcus and lymphocytes rates. Moreover, Faecalibacterium and Ruminococcus 2 contributed to the increase of the monocytes compartment. Conversely, Rothia and Clostridium sensu stricto 1 negatively correlated with neutrophil restoration.
The interaction between the immune system and gut microbiota is a cross talk. Different bacteria are able to influence the source of WBCs in the bone marrow and their tissue destination but the immune system can modulate microbiota composition as well. The better understanding of the latter relationship was the focus of the second part of J. Schuler et Al. study.
Interestingly, the taxa that positively correlated with WBC were mainly obligate anaerobes such as Ruminococcus, Faecalibacterium and Akkermansia. The same kind of bacteria were the ones that more easily colonized the gut after auto-FMT. This may explain the higher WBCs counts in patients receiving the fecal transplant right after chemotherapy and HCT.
Eventually, Ruminococcus 2, Faecalibacterium and Akkermansia have the most impactful role on immune cell development, proliferation and reconstitution after haematopoietic cell transplantation. Since HCT can affect their abundance, a poor WBCs count restoration after the transplant could be related to severe and excessive damages to the aforementioned bacterial genera. Enriching the microbiota of patients in these genera could be an innovative approach to induce a faster and more efficient immune cells reconstitution, considering that they are able to greatly accelerate the process even without the cooperation of immunostimulatory drugs.