Microbiota long-term dynamics and prediction of acute graft-versus-host disease in pediatric allogeneic stem cell transplantation

Abstract

Background Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) exhibit changes in their gut microbiota and are experiencing a range of complications, including acute graft-versus-host disease (aGvHD). It is unknown if, when, and under which conditions a re-establishment of microbial and immunological homeostasis occurs. It is also unclear whether microbiota long-term dynamics occur at other body sites than the gut such as the mouth or nose. Moreover, it is not known whether the patients’ microbiota prior to HSCT holds clues to whether the patient would suffer from severe complications subsequent to HSCT. Here, we take a holobiont perspective and performed an integrated host-microbiota analysis of the gut, oral, and nasal microbiota in 29 children undergoing allo-HSCT. Results The bacterial diversity decreased in the gut, nose, and mouth during the first month and reconstituted again 1–3 months after allo-HSCT. The microbial community composition traversed three phases over 1 year. Distinct taxa discriminated the microbiota temporally at all three body sides, including Enterococcus spp., Lactobacillus spp., and Blautia spp. in the gut. Of note, certain microbial taxa appeared already changed in the patients prior to allo-HSCT as compared with healthy children. Acute GvHD occurring after allo-HSCT could be predicted from the microbiota composition at all three body sites prior to HSCT. The reconstitution of CD4+ T cells, TH17, and B cells was associated with distinct taxa of the gut, oral, and nasal microbiota. Conclusions This study reveals for the first time bacteria in the mouth and nose that may predict aGvHD. Monitoring of the microbiota at different body sites in HSCT patients and particularly through involvement of samples prior to transplantation may be of prognostic value and could assist in guiding personalized treatment strategies. The identification of distinct bacteria that have a potential to predict post-transplant aGvHD might provide opportunities for an improved preventive clinical management, including a modulation of microbiomes. The host-microbiota associations shared between several body sites might also support an implementation of more feasible oral and nasal swab sampling-based analyses. Altogether, the findings suggest that the microbiota and host factors together could provide actionable information to guiding precision medicine.

Long-Term Analysis of Resilience of the Oral Microbiome in Allogeneic Stem Cell Transplant Recipients

“…At that time, the oral microbiome is most different from pre-SCT conditions. The present study, as well as our previous study in autoSCT recipients and the study of Ingham et al, showed that the oral microbiome is resilient as it returns to pre-SCT levels three months after SCT, remaining relatively stable in the first 12 to 18 months following SCT [10,15].…”

“…The decrease in oral bacterial diversity after SCT has been described by our group after autologous SCT [10] and by others in both adults and children in alloSCT and autoSCT patients [9,[14][15][16][31][32][33]. Most studies described a significant change in microbial composition directly after SCT.…”

“…Most studies described a significant change in microbial composition directly after SCT. Changes in the oral microbiome were related to oral mucositis in adults [9,10,16,31,32] or to acute GVHD anywhere in the body in adult patients [14] or children [15]. Almost all the studies lack data on the recovery of the oral microbiome as these studies ended at three to four weeks after SCT.…”

“…A number of studies described changes in the oral microbiome early after cancer treatment [9][10][11][12][13][14][15]. Several genera, including Staphylococcus and Enterococcus, and loss of microbiome diversity were associated with oral mucositis [9,10,12,16].…”

Exposure to food additive mixtures in 106,000 French adults from the NutriNet-Santé cohort

“…A potential role in the development of Chron's disease has also been suggested for lecithins 95 – 97 , and an experimental study among humans suggests a link between lecithins and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO) 94 . In a study on ex-vivo models of human microbiota, 20 emulsifiers were tested and a large majority (including carboxymethylcellulose, polysorbate 80, carrageenans, guar/xanthan gums, lecithins), were able to directly modify the gut microbiota in a way that could promote gut inflammation 23 . Carrageenans have been linked to fasting hyperglycemia and exacerbated glucose intolerance and hyperlipidemia without effect on weight in mice 31 .…”