Butyrate functions in concert with myeloid-derived suppressor cells recruited by CCR9 to alleviate DSS-induced murine colitis.

Ulcerative colitis (UC) is a precancerous disease caused mainly by a combination of genetic susceptibility, environmental factors and microbiota dysbiosis. As a kind of short-chain fatty acid (SCFA), butyrate has been shown to be closely related to the progression of colitis. However, the exact regulatory mechanism of butyrate in colitis needs to be further elucidated. In our current research, the effects of butyrate were examined in a dextran sulfate sodium (DSS)-induced murine colitis model, which simulates human UC. The administration of butyrate significantly reversed the signs of colitis and alleviated colonic histological damage in DSS­induced colitis. The transcription levels of the main proinflammatory mediators, including tumor necrosis factor-α, interleukin-6 and interleukin-12, were also reduced, as determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). This indicates that butyrate could alleviate DSS-induced colitis by inhibiting proinflammatory mediators. In addition, we found that myeloid-derived suppressor cells (MDSCs), which have an inflammation-relieving effect, did not effectively alleviate DSS­induced colitis but showed a compensatory increase in the DSS group. However, the compensatory increase in MDSCs in the DSS group significantly decreased after butyrate treatment. Moreover, the chemokine receptor CCR9, which mediates the homing of intestinal immune cells, also showed consistent changes similar to MDSCs. Butyrate alone did not have the aforementioned effects on mice. Thus, butyrate may effectively relieve DSS­induced colitis by synergistic regulatory effects with MDSCs, which migrate and gather through CCR9 recruitment.

High fat diet exacerbates dextran sulfate sodium induced colitis through disturbing mucosal dendritic cell homeostasis.

Epidemiological studies have shown that fat rich western diet contributes to the high incidence of inflammatory bowel disease (IBD). Moreover, accumulated data indicated that fat dietary factor might promote the change of the composition and metabolism in commensal flora. But, the exact mechanisms for fatty diet in gut inflammation are not well demonstrated. In this study, we found that high fat diet (HFD) promoted inflammation and exacerbated the disease severity of dextran sulfate sodium (DSS) induced colitis in mice. Compared with low fat diet (LFD)/DSS mice, shorter colon length, more epithelial loss and crypt destruction and more Gr-1+ myeloid inflammatory cells infiltration in colons were observed in HFD/DSS cohorts. Interestingly, such HFD mediated inflammation accompanied with the dys-regulation of hematopoiesis, and more hematopoiesis stem and progenitor cells were detected in colon and spleen. We further analyzed the effects of HFD and DSS treatment on mucosal DC subsets, and found that DSS treatment in LFD mice mainly dramatically increased the percentage of CD11c+CD103-CD11b+ DCs in lamina propria (LP). While, in HFD/DSS mice, HFD pre-treatment not only increased the percentage of CD11c+CD103-CD11b+ DCs, but also decreased CD11c+CD103+CD11b+ in both LP and mesenteric lymph nodes (MLN) in mice with colitis. This disequilibrium of mucosal dendritic cells in HFD/DSS mice may depend on the reduced levels of buytrate and retinoic acid. Thus, this study declared the effects of HFD on gut microenviroment, and further indicated its potential role in the development of DSS induced colitis.

Dietary fish oil exacerbates concanavalin A induced hepatitis through promoting hepatocyte apoptosis and altering immune cell populations.

The development of hepatitis is associated with the infiltration and activation of immune cells in liver. N-3 polyunsaturated fatty acids (n-3 PUFAs) rich fish oil (FO) is used to prevent and treat inflammatory diseases. But, the effects of dietary FO on autoimmune hepatitis remain largely unknown. In this study, Concanavalin A (Con A) induced hepatitis was used to evaluate the actions of dietary FO. Unexpectedly, 2-week FO treatment had not shown any protection, on the contrary, exacerbated liver injury in this hepatitis model. The levels of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) statistically increased from 10,501 ± 2,154 and 30,394 ± 2,420 in low fat diet (LFD)/Con A group to 17,579 ± 693 and 49,439 ± 4,628 in FO/Con A group. Simultaneously, FO diet induced more necrotic liver tissues and apoptotic hepatocytes, and up-regulated the hepatic expression of TNF-α and IFN-γ after Con A challenge. Interestingly, FO promoted severe liver injury was accompanied by decreasing the percentage of CD4⁺ T cell, NK1.1⁺ cells and CD8⁺ T cells in CD45⁺ liver non-parenchymal hepatic cells (NPCs) through inducing apoptosis. Further experiments declared 2-week FO diet intake firstly increased the proportion of CD11b⁺Gr-1(hi) neutrophils in liver, but then dramatically expanded CD11b⁺Gr-1(int) inflammatory monocytes population after Con A administration. Collectively, our study indicated that high FO intake not only aggravated liver injury, but also altered the population of immune cells in liver. Thus, these results indicated that when dietary FO was used to benefit health in autoimmune diseases, its potential risks of side effect also need paying close attention.