Marine Chitooligosaccharide Alters Intestinal Flora Structure and Regulates Hepatic Inflammatory Response to Influence Nonalcoholic Fatty Liver Disease

Abstract

In this study, C57BL/6 mice were given an HFHSD diet for 8 weeks to induce hepatic steatosis and then given COSM solution orally for 12 weeks. The study found that the HFHSD diet resulted in steatosis and insulin resistance in mice. The formation of NAFLD induced by HFHSD diet was related to the imbalance of intestinal flora. However, after COSM intervention, the abundance of beneficial bacteria increased significantly, while the abundance of harmful bacteria decreased significantly. The HFHSD diet also induced changes in intestinal bacterial metabolites, and the content of short-chain fatty acids in cecal contents after COSM intervention was significantly higher than that in the model group. In addition, COSM not only improved LPS levels and barrier dysfunction in the ileum and colon but upregulated protein levels of ZO-1, occludin, and claudin in the colon and downregulated the liver LPS/TLR4/NF-κB inflammatory pathway. We concluded that the treatment of marine chitooligosaccharide COSM could improve the intestinal microflora structure of the fatty liver and activate an inflammatory signaling pathway, thus alleviating the intrahepatic lipid accumulation induced by HFHSD.

Intestinal flora: A new target for traditional Chinese medicine to improve lipid metabolism disorders

“…CA (Mu et al, 2021) decreased LPS/TLR4, an LPS-mediated inflammatory pathway, and reduced TNF-α, IL-6 levels, thereby inhibiting dysregulation of lipid metabolism. LBPs (Gao et al, 2021) and COSM (Feng et al, 2022) inhibited indicators related to hepatic LPS/TLR4/NF-κB signaling pathway and attenuated the level of inflammation. HQT (Tang, 2019) and Compound Danshen Dripping Pills selectively targeted TLR4 and inhibited LPS-induced inflammatory mediator production by attenuating the LPS/TLR4/MyD88 pathway.…”

“…The abundance of Desulfovibrio, a producer of LPS, was positively correlated with inflammation and LMD. Danlou Tablet (DLT) (Sun et al, 2020), DZSM (Guo et al, 2022), GQD (Liu, 2019), SLBZ (Zhang et al, 2018), DG (Li Y. et al, 2018), Chitooligosaccharide (COSM) (Feng et al, 2022), Rhizoma Coptidis (RC) alkaloids (He et al, 2016), Baicalin (Liu, 2016), Quercetin (Porras et al, 2017) and BBR (Xu, 2013) might ameliorate LMD by decreasing the abundance of Desulfovibrio to reduce LPS into the blood and inflammatory factors secretion. Notably, DLT (Sun et al, 2020), Gastrodin (Liu F. Y. et al, 2021) could downregulate the levels of inflammatory markers IL-1β, ICAM-1 and TNF-α, favoring the reversal of periaortic inflammation and reduction of plaque area in AS mice.…”

“…LC (Zhang et al, 2019), DLT (Sun et al, 2020), NXT (Lu et al, 2022), IPTS (Ba et al, 2022), LJP (Zhang et al, 2021d), LBPs (Gao et al, 2021), Zanthoxylum bungeanum Maxim. [Rutaceae; Zanthoxyli pericarpium] (ZB) (You, 2016), Ginkgo biloba extract (GbE) , Inulin (Bao, 2021;, NFP (Yang et al, 2020), TP (Wang et al, 2018), Bilberry anthocyanins (Nakano et al, 2020) and COSM (Feng et al, 2022) significantly improved serum lipid levels (TC, TG) as well as reducing lipid accumulation, which may be associated with modifying intestinal flora and increasing SCFAs levels. In-depth research revealed that Compound Danshen Dripping Pills and JZG intervention elevated the abundance of Lachnospiraceae; Qingxin Jieyu Granule (QXJY) (Wang, 2019) and water insoluble polysaccharide WIP (Sun et al, 2019) intervention increased Clostridium abundance; Macroalgae Laminaria japonica (MLJ) (Zhang Q. et al, 2020), Quercetin (Porras et al, 2017), Myricetin (Sun et al, 2021), MC (Bai, 2019) and GLP (Sang et al, 2021) administration improved the abundance of Allobaculum; Erchen decoction (ECD) and EGCG (Zuo, 2020) administration enhanced the abundance of Roseburia; HGQZ (Tang, 2019) and DG (Li Y. et al, 2018) treatment increased the abundance of Ruminococcaceae; SLBZ (Hong, 2021) and DZSM (Guo et al, 2022) administration enriched the abundance of Bifidobacterium, Lactobacillus; Guanxinning Tablet (GXNT) (Yang Q. et al, 2022), Black tea polyphenols (BTP) (Henning et al, 2018) and RLPs (Zhang X. J., 2020) treatment all increased the relative abundance of Prevotella; G. pentaphyllum saponins (GPS) (Zhong F. W. et al, 2022) administration enriched the abundance of Bacteroides.…”

Preventive and therapeutic effects of natural products and herbal extracts onnonalcoholic fatty liver disease/nonalcoholic steatohepatitis

“…Feng et al revealed that COSM could dose‐dependently reduce IL‐6 levels and TNF‐α levels to attenuate inflammatory responses in NAFLD mice; serum LPS levels (representing the degree of intestinal barrier obstruction) were also significantly decreased in the COSM group. Additionally, COSM was able to improve intestinal barrier structure by increasing beneficial bacteria such as thick‐walled and proteobacteria in NAFLD mice as well as inhibit LPS/TLR4/NF‐κB signaling pathway (Feng et al, 2022).…”

“…Additionally, COSM was able to improve intestinal barrier structure by increasing beneficial bacteria such as thick-walled and proteobacteria in NAFLD mice as well as inhibit LPS/TLR4/NF-κB signaling pathway (Feng et al, 2022).…”