Dietary ethanolamine plasmalogen alleviates DSS-induced colitis by enhancing colon mucosa integrity, antioxidative stress, and anti-inflammatory responses

Nguma E, Yamashita S, Han K, Otoki Y, Yamamoto A, Nakagawa K, Fukushima M, Miyazawa T, and Kinoshita M. (2021) Dietary ethanolamine plasmalogen alleviates DSS-induced colitis by enhancing colon mucosa integrity, antioxidative stress, and anti-inflammatory responses via increased ethanolamine plasmalogen molecular species: Protective role of vinyl ether linkages. Journal of Agricultural and Food Chemistry

Ulcerative colitis (UC) is an intestinal disorder caused by prolonged inflammation affecting the mucosal surface of the colon. This results in epithelial dysfunction and an increase in mucosal permeability in the colon. A person with UC can experience abdominal pain, diarrhea, rectal bleeding, or weight loss. The inflammation experienced is the result of infiltrating neutrophils, lymphocytes, monocytes, macrophages, and plasma cells as well as an excess of reactive oxygen species (ROS), proinflammatory mediators, and apoptosis signals which leads to ulceration. In addition, genetic predisposition and environmental factors such as smoking, stress, hormone imbalance, vitamin D, and diet can play a role in the onset of UC, however a singular cause is not known. Dietary fat has been associated with the risk of UC with the intake of n-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) being associated with a reduced risk of UC and the intake of n-6 PUFAs, such as linoleic acid and arachidonic acid (ARA) increasing the risk of UC. Plasmalogens are a class of lipid that contain a vinyl-ether bond at sn-1 and at sn-2 is a PUFA, either EPA or DHA in marine sources or ARA in land sources. As plasmalogens are known to have roles in membrane structure, scavenging ROS, and would provide PUFAs, Nguma et al were interested in the role of dietary plasmalogens in a mouse model of colitis.

A mouse model of colitis was created through induction from dextran sodium sulfate (DSS), a synthetic sulfated polysaccharide which produces similar clinical and histological characteristics to human UC. After UC was induced, the mice were fed either a diet containing 0.1% ethanolamine glycerophospholipids (EtnGpls) from either ascidian muscle or porcine liver. It is important to note that ascidian muscle EtnGpls were found to contain 86.2% plasmalogens while porcine liver EtnGpls was only 7.7% plasmalogens and that the porcine liver had a lower ratio of EPA + DHA to ARA compared to ascidian muscle (6.1 and 29.1, respectively). Four days after the onset of DSS induction, the control group had a significantly higher body weight compared to the DSS group. As well, the group treated with the ascidian muscle diet had a higher body weight compared to the DSS group, but the weights of the porcine liver diet-fed group were not different from the DSS group.

After 16 days of the study, the colon length was the same in the DSS and DSS + either EtnGpls diets, and was significantly longer in the control group as expected. In addition, tissue sections from the control group showed normal morphology of colon crypts and epithelium, but the DSS group demonstrated severe disruption of both structures. Interestingly, the ascidian muscle diet-fed and the porcine liver diet-fed mice showed an intermediate level of damage between the DSS group and the control group. As well, there was less damage in the ascidian muscle-fed group compared to the porcine liver-fed group, suggesting that the ascidian muscle EtnGpls were more effective at recovering the disruption caused by DSS-induced colitis.

To demonstrate whether the diets influenced apoptosis-related proteins in the colon mucosa such as antiapoptotic proteins Bcl-2 (B-cell lymphoma 2) and p27, cleaved caspase-3 apoptosis executioner protein, and TNF R1 death receptor protein were analyzed. All four were found to be upregulated in the DSS group compared to the control group indicating a higher level of apoptosis activity. The group fed the ascidian muscle-diet had a significant downregulation of the levels of cleaved caspase 2 protein and TNF R1 death receptor protein compared to the DSS group.

Nguma et al were able to determine efficacy of a EtnGpl-enriched diet in recovering a DSS-induced colitis model. Although both treatments generally were advantageous, the diet containing EtnGpls from ascidian muscle showed the greatest improvement. As this treatment had a higher plasmalogen content and greater level of EPA and DHA chains, where the consumption of either is associated with a reduced risk of UC, it is unsurprising that the ascidian muscle was more successful. It was able to improve the weight of the mice, the disruption of colon crypts and epithelium, and downregulate some apoptotic-related proteins in the mice. This study is the first account of treating colon inflammation in DSS-induced colitis with dietary plasmalogens and was largely successful. Further work into the use of a plasmalogen treatment for colitis, or its potential as a preventative measure, could provide a new therapeutic avenue for people who experience this intestinal disorder.