Abstract
Mucositis is an inflammatory condition of the gut, caused by an adverse effect of chemotherapy drugs, such as 5-fluorouracil (5-FU). In an attempt to develop alternative treatments for the disease, several research groups have proposed the use of probiotics, in particular, Lactic Acid Bacteria (LAB). In this context, the use of recombinant LAB, for delivering anti-inflammatory compounds has also been explored. In previous work, we demonstrated that either Lactococcus lactis NZ9000 or a recombinant strain expressing an antimicrobial peptide involved in human gut homeostasis, the Pancreatitis-associated Protein (PAP), could ameliorate 5-FU-induced mucositis in mice. However, the impact of these strains on the gut microbiota still needs to be elucidated. Therefore, in the present study, we aimed to characterize the effects of both Lactococci strains in the gut microbiome of mice through a 16 S rRNA gene sequencing metagenomic approach. Our data show 5-FU caused a significant decrease in protective bacteria and increase of several bacteria associated with pro-inflammatory traits. The Lactococci strains were shown to reduce several potential opportunistic microbes, while PAP delivery was able to suppress the growth of Enterobacteriaceae during inflammation. We conclude the strain secreting antimicrobial PAP was more effective in the control of 5-FU-dysbiosis.
Highlights
Oncology treatments based on chemotherapy or radiotherapy are responsible for the occurrence of a gastrointestinal inflammatory condition known as mucositis[1,2,3]
Our research group evaluated the beneficial effect of a recombinant strain of L. lactis NZ9000 producing an antimicrobial peptide (AMP) isolated from human, the Pancreatitis-associated Protein (PAP), into mice exposed to 5-FU24
The high-throughput sequencing generated more than 135 megabases (Mb) for the enriched 16 rRNA gene V4 regions from all 72 samples, representing a total of 4.784.028 reads
Summary
Oncology treatments based on chemotherapy or radiotherapy are responsible for the occurrence of a gastrointestinal inflammatory condition known as mucositis[1,2,3]. The treatment of gastrointestinal mucositis relies mostly on antibiotics and analgesics administration and since the efficiency of current therapies in alleviating this pathology has been questioned, several research groups are currently investigating alternative rationales[13] In this context, promising achievements with probiotics, mainly members of the Lactic Acid Bacteria (LAB) group, have been reported in animal models of mucositis and seems to be useful to maintain intestinal barrier function[14,15,16,17,18,19,20,21]. Our research group evaluated the beneficial effect of a recombinant strain of L. lactis NZ9000 producing an antimicrobial peptide (AMP) isolated from human, the Pancreatitis-associated Protein (PAP), into mice exposed to 5-FU24 This AMP is naturally secreted by Paneth cells in mammalian small intestines and seems to be involved in the protection of the host by killing harmful bacteria and preventing the microbe-driven inflammatory process[25]. As L. lactis NZ9000 has shown protective effects in the same model, we addressed its effects on the gut microbiome as well
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