Since December 2019, a global pandemic has been observed, caused by the emergence of a new coronavirus, SARS CoV-2. The latter is responsible for the respiratory disease, COVID-19. The infection is also characterized by renal, hepatic, and gastrointestinal dysfunctions suggesting the spread of the virus to other organs. A dysregulated immune response was also reported. To date, there is no measure to treat or prevent SARS CoV-2 infection. Additionally, as gut microbiota composition is altered in patients with COVID-19, alternative therapies using probiotics can be considered to fight SARS CoV-2 infection. This review aims at summarizing the current knowledge about next-generation probiotics (NGPs) and their benefits in viral respiratory tract infections and in COVID-19. We describe these bacteria, highlighted by studies using metagenomic approaches. In addition, these bacteria generate metabolites such as butyrate, desaminotyrosine, and secondary bile acid, suggested to prevent viral respiratory infections. Gut microbial metabolites transported via the circulation to the lungs could inhibit viral replication or improve the immune response against viruses. The use of probiotics and/or their metabolites may target either the virus itself and/or the immunologic process. However, this review showed that more studies are needed to determine the benefits of probiotics and metabolite products in COVID-19.

The gut microbiota contributes to human health and disease; however, the mechanisms by which commensal bacteria interact with the host are still unclear. To date, a number of in vitro systems have been designed to investigate the host–microbe interactions. In most of the intestinal models, the enteroendocrine cells, considered as a potential link between gut bacteria and several human diseases, were missing. In the present study, we have generated a new model by adding enteroendocrine cells (ECC) of L-type (NCI-H716) to the one that we have previously described including enterocytes, mucus, and M cells. After 21 days of culture with the other cells, enteroendocrine-differentiated NCI-H716 cells showed neuropods at their basolateral side and expressed their specific genes encoding proglucagon (GCG) and chromogranin A (CHGA). We showed that this model could be stimulated by commensal bacteria playing a key role in health, Roseburia intestinalis and Bacteroides fragilis, but also by a pathogenic strain such as Salmonella Heidelberg. Moreover, using cell-free supernatants of B. fragilis and R. intestinalis, we have shown that R. intestinalis supernatant induced a significant increase in IL-8 and PYY but not in GCG gene expression, while B. fragilis had no impact. Our data indicated that R. intestinalis produced short chain fatty acids (SCFAs) such as butyrate whereas B. fragilis produced more propionate. However, these SCFAs were probably not the only metabolites implicated in PYY expression since butyrate alone had no effect. In conclusion, our new quadricellular model of gut epithelium could be an effective tool to highlight potential beneficial effects of bacteria or their metabolites, in order to develop new classes of probiotics.