Recent evidence suggests that probiotics can restore the mucosal barrier integrity, ameliorate inflammation, and promote homeostasis required for metabolism in obesity by affecting the gut microbiota composition. In this study, we investigated the effect of Akkermansia muciniphila and its extracellular vesicles (EVs) on obesity-related genes in microarray datasets and evaluated the cell line and C57BL/6 mice by conducting RT-PCR and ELISA assays. A. muciniphila-derived EVs caused a more significant loss in body and fat weight of high-fat diet (HFD)-fed mice, compared with the bacterium itself. Moreover, treatment with A. muciniphila and EVs had significant effects on lipid metabolism and expression of inflammatory markers in adipose tissues. Both treatments improved the intestinal barrier integrity, inflammation, energy balance, and blood parameters (i.e., lipid profile and glucose level). Our findings showed that A. muciniphila-derived EVs contain various biomolecules, which can have a positive impact on obesity by affecting the involved genes. Also, our results showed that A. muciniphila and its EVs had a significant relationship with intestinal homeostasis, which highlights their positive role in obesity treatment. In conclusion, A. muciniphila-derived EVs can be used as new therapeutic strategies to ameliorate HFD-induced obesity by affecting various mechanisms.

Several studies have reported that the host-microbe interactions in the gut modulate the host serotonin or 5-hydroxytryptamine (5-HT) system. Here, we evaluated the effects of Akkermansia muciniphila and its extracellular vesicles (EVs) on genes pertaining to the serotonergic system in the colon and hippocampus of mice. Male C57BL/6J mice were administered viable A. muciniphila and its EVs for 4 weeks. The serotonin levels in the colon, hippocampus, and serum of mice, as well as the human colon carcinoma cells (Caco-2), were measured by ELISA assays. Also, the effects of A. muciniphila and its EVs on the expression of serotonin system genes in the colon and hippocampus were examined. A. muciniphila and its EVs may have a biological effect on the induction of serotonin levels in the colon and hippocampus of mice. Also, EVs increased the serotonin level in the Caco-2 cell line. In contrast, both treatments decreased the serotonin level in the serum. Both the bacterium and its EVs had significant effects on the mRNA expression of genes, involved in serotonin signaling/metabolism in the colon and hippocampus of mice. Moreover, A. muciniphila and its EVs affected the mRNA expression of inflammatory cytokines (Il-10 and Tnf-α) in the colon, however, there is no significant difference in inflammatory cell infiltrate in the histopathology of the colon. The presence of A. muciniphila and its EVs in the gut promotes serotonin concentration, they also affect serotonin signaling/metabolism through the gut-brain axis and may be considered in new therapeutic strategies to ameliorate serotonin-related disorders.

Considering the important role of microbiome, many of current investigations have focused on its beneficial aspects. Although, research explores new dimensions of the impact of microbiome and examines the differences in patients and healthy individuals for identifying biomarker patterns, but limited information is available, and investigation in this field seems to be of great value. On the other hand, new therapeutic approaches, called personalized medicine, have opened a new window in medical science, and the association between microbiome and personalized medicine seems to be one of the most interesting aspects of the subsequent research, and has a pivotal perspective on the treatment of diseases such as cancer. Accordingly, given the novelty of the relationship between these two axes, there are very few studies in this regard. The presence of specific strains may have the ability to modulate cancer progression and therapeutics; this increases the likelihood of precision medicine in relation to microbiota, in terms of treatment and prognosis, and therefore, microbiota is a next generation medicine and may develop a novel therapeutic action in this field.

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