Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice

Abstract

The gut microbiota is a contributing factor in obesity-related metabolic disorders. The effect of metformin on the gut microbiota has been reported; however, the relationship between the gut microbiota and the mechanism of action of metformin in elderly individuals is unclear. In this study, the effect of metformin on the gut microbiota was investigated in aged obese mice. The abundance of the genera Akkermansia, Bacteroides, Butyricimonas, and Parabacteroides was significantly increased by metformin in mice fed a high-fat diet. Metformin treatment decreased the expression of IL-1β and IL-6 in epididymal fat, which was correlated with the abundance of various bacterial genera. In addition, both fecal microbiota transplantation from metformin-treated mice and extracellular vesicles of Akkermansia muciniphila improved the body weight and lipid profiles of the mice. Our findings suggest that modulation of the gut microbiota by metformin results in metabolic improvements in aged mice, and that these effects are associated with inflammatory immune responses.

An in vitro model maintaining taxon-specific functional activities of the gut microbiome

“…A high level of IVIVC at the phylum level, especially for day 14 samples, was indicated with Pearson's correlation of r = 0.93 ± 0.02 ( Figure 3B). Furthermore, at the genus level, we observed a consistent increase in the genera Akkermansia, Bacteroides and Parabacteroides ( Figure 3C) under both in vitro and in vivo conditions, the in vivo change was agreement with the previously reported studies 5,41,42 . At the species level, three separate groups of PLS-DA analyses were performed by comparing untreated microbiome versus microbiome following in vivo 14-and 28-day and in vitro 24 hr metformin treatment, respectively.…”

“…Metformin is a widely prescribed drug for treating type 2 diabetes and it has been reported that in human 30% of the oral dose can be recovered in ers he for in feces 40 . Several studies have focused on the effect of metformin on gut microbiota composition and functions 5,6,41 . For these reasons, we employed metformin to validate our MiPro model against in vivo studies by investigating the impact of metformin exposure on gut microbial communities in mice and in our model.…”

Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals

“…is colonised by a unique microbial community, including species such as Bacteroides fragilis and Akkermansia muciniphila 11,12 . The importance of A. muciniphila is only starting to emerge in connection with several diseases: it is most beneficial to the host, although an excess has been linked to pathologies such as multiple sclerosis 13 and Parkinson's disease 14 .…”

Potential correlation between carbohydrate‐active enzyme family 48 expressed by gut microbiota and the expression of intestinal epithelial AMP‐activated protein kinase β

“…Additionally, members of the Lachnospiraceae and Erysipelotrichaceae families have previously been suggested to be associated with microbe TMA generation and development of atherosclerosis (Qiu, Tao, Xiong, Yu, & Wei, 2018). These species have been suggested as playing a role in inhibiting obesity as well as improving intestinal barrier function, possibly through interaction with host intestinal epithelial cells via mucoprotein(Berry et al, 2012;Depommier et al, 2019;Lee et al, 2018).The differences in the gut microbial species from different experimental groups were further defined using LEfSe analysis (Figure 4). The composition of the gut microbiota at the phylum and genus levels induced by the experimental diets is shown in Figure 3.…”

“…without AMPK inhibition). These species have been suggested as playing a role in inhibiting obesity as well as improving intestinal barrier function, possibly through interaction with host intestinal epithelial cells via mucoprotein(Berry et al, 2012;Depommier et al, 2019;Lee et al, 2018).The differences in the gut microbial species from different experimental groups were further defined using LEfSe analysis (Figure 4). Species from Firmicutes phylum, Dubosiella, Chlamydia, Enterorhabdus, and Clostridium were identified to be significantly enriched in the mice fed with a red meat diet, potentially indicating a relatively unhealthy gut environment as these species have been associated with dysbiosis or pathogenicity (Kociolek & Gerding, 2016; Leclercq et al, 2017; Zhang et al, 2018).…”