The intestinal microbiota of dogs consists of bacteria, fungi, archaea, viruses and protozoa, and intestinal bacteria have been implicated in several types of cancer [3-7]. Animal models play a key role in understanding the importance of gut microbiota composition in immune system development, and its relation with health and disease. Microbes can influence immune cells directly, indirectly, or both, and led to an increased lymphocyte proliferation with a higher chance of aberrant DNA replication, particularly in some B lymphocytes which are innately vulnerable to genetic instability and activation. Also oxidative stress caused by intestinal microbiota, either directly or indirectly through the immune system, can affect tumorigenesis, thus, the microbiota can affect several pathways associated with lymphomagenesis [7]. The optimal responses to cancer therapy require an intact commensal microbiota that mediates its effects, by modulating myeloid derived cell functions in the tumour microenvironment [1]. A recent study showed significant differences in the microbial communities of dogs presenting with multi-centric lymphoma compared to healthy control dogs [2]. In our study design we analysed the microbiome (by using 16S rRNA gene Illumina sequencing and qPCR assays) of naturally voided fecal samples from 12 healthy dogs, 12 lymphoma affected dogs before (pre) and after (post) induction phase (8 weeks) of chemotherapy (cyclophosphamide, vincristine, and prednisolone) plus probiotics (B. clausii or S. thermophilus, L. acidophilus, L. plantarum, L. casei, L. helveticus, L. brevis, 2B. lactis). All dogs were affected by B cell lymphoma, generalized lymphadenopathy form (multicentric), stage III or IV (WHO clinical staging for lymphoma) without systemic signs. Animals selected were not showing any additional clinical signs of significant disease, and were in good general conditions. None of the dog showed any gastrointestinal signs in the previous two months, and none received antibiotics within at least the previous 2 months before fecal sample collection. Several statistically significant data were observed comparing the fecal microbiome of healthy dogs vs lymphoma dogs before and after chemotherapy plus probiotics. In particular, higher concentrations in healthy dogs compared to lymphoma dogs were observed for Faecalibacterium (P<0.001, healthy vs pre and post chemotherapy) and Turicibacter (P< 0.01 healthy vs post chemotherapy). On the contrary, the concentration of E.coli (P< 0.01) and Streptococcus (P<0.05) was higher in lymphoma dogs post chemotherapy compared to healthy dogs. In conclusion, this study showed significant differences in the fecal microbial communities of dogs presenting with multi-centric lymphoma undergoing chemotherapy compared to healthy dogs but not between microbiota pre vs post chemotherapy. In order to understand microbiome’s changes in 58 lymphoma affected dogs treated with standard protocol plus probiotics, a larger number of patients and stool samples, before and after treatment, should be investigated.

Fecal microbiota differences in canine lymphoma treated with chemotherapy and probiotics

George Lubas;
2018

Abstract

The intestinal microbiota of dogs consists of bacteria, fungi, archaea, viruses and protozoa, and intestinal bacteria have been implicated in several types of cancer [3-7]. Animal models play a key role in understanding the importance of gut microbiota composition in immune system development, and its relation with health and disease. Microbes can influence immune cells directly, indirectly, or both, and led to an increased lymphocyte proliferation with a higher chance of aberrant DNA replication, particularly in some B lymphocytes which are innately vulnerable to genetic instability and activation. Also oxidative stress caused by intestinal microbiota, either directly or indirectly through the immune system, can affect tumorigenesis, thus, the microbiota can affect several pathways associated with lymphomagenesis [7]. The optimal responses to cancer therapy require an intact commensal microbiota that mediates its effects, by modulating myeloid derived cell functions in the tumour microenvironment [1]. A recent study showed significant differences in the microbial communities of dogs presenting with multi-centric lymphoma compared to healthy control dogs [2]. In our study design we analysed the microbiome (by using 16S rRNA gene Illumina sequencing and qPCR assays) of naturally voided fecal samples from 12 healthy dogs, 12 lymphoma affected dogs before (pre) and after (post) induction phase (8 weeks) of chemotherapy (cyclophosphamide, vincristine, and prednisolone) plus probiotics (B. clausii or S. thermophilus, L. acidophilus, L. plantarum, L. casei, L. helveticus, L. brevis, 2B. lactis). All dogs were affected by B cell lymphoma, generalized lymphadenopathy form (multicentric), stage III or IV (WHO clinical staging for lymphoma) without systemic signs. Animals selected were not showing any additional clinical signs of significant disease, and were in good general conditions. None of the dog showed any gastrointestinal signs in the previous two months, and none received antibiotics within at least the previous 2 months before fecal sample collection. Several statistically significant data were observed comparing the fecal microbiome of healthy dogs vs lymphoma dogs before and after chemotherapy plus probiotics. In particular, higher concentrations in healthy dogs compared to lymphoma dogs were observed for Faecalibacterium (P<0.001, healthy vs pre and post chemotherapy) and Turicibacter (P< 0.01 healthy vs post chemotherapy). On the contrary, the concentration of E.coli (P< 0.01) and Streptococcus (P<0.05) was higher in lymphoma dogs post chemotherapy compared to healthy dogs. In conclusion, this study showed significant differences in the fecal microbial communities of dogs presenting with multi-centric lymphoma undergoing chemotherapy compared to healthy dogs but not between microbiota pre vs post chemotherapy. In order to understand microbiome’s changes in 58 lymphoma affected dogs treated with standard protocol plus probiotics, a larger number of patients and stool samples, before and after treatment, should be investigated.
978-88-6768-034-4
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/937605
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