Implication of Gut Microbiota in Cardiovascular Diseases

Figure 2

Manners of cell death induced by gut microbiota. A variety of gut flora have been demonstrated to be effective in regulating cell death. (a) Muciniphila and (b) fragilis were shown to counteract apoptosis. In contrast, sodium propionate has the ability to induce apoptosis. Interestingly, the effects of butyrate on apoptosis are controversial, manifesting elevated biomarkers such as P21, Bad, Bax, and caspase-3. In addition, SCFAs stimulate autophagy, while Bifidobacterium is autophagy-protective, with decreased expression of P62, Beclin1, and LC3II. Sodium butyrate promotes autophagy by inhibiting the PI3K/Akt/mTOR pathway. Additionally, it is involved in pyroptosis via regulation of the caspase-1/gasdermin D pathway. In addition, TMAO stimulates ROS activation and thus induces pyroptosis. Along with pyroptosis, the NLRP3/NLRP6 inflammasome and IL-1β are produced. Moreover, clockophagy can reverse gut dysbiosis. For instance, SCFAs are capable of controlling rhythmicity via clock genes such as Bmal1.