Alterations in Gut Microbiota and Upregulations of VPAC2 and Intestinal Tight Junctions Correlate with Anti-Inflammatory Effects of Electroacupuncture in Colitis Mice with Sleep Fragmentation

Abstract

The relationship between inflammatory bowel disease and sleep disturbances is complicated and of increasing interest. We investigated the inflammatory and immunological consequences of EA in sleep-deprived colitis and found that dextran sulfate sodium (DSS)-induced colitis in sleep-fragmented (SF) mice was more severe than that in mice with normal sleep. This increase in the severity of colitis was accompanied by reduced body weight, shortened colon length, and deteriorated disease activity index. DSS with SF mice presented obvious diminished intestinal tight junction proteins (claudin-1 and occludin), elevated proinflammatory cytokines (CRP, IFN-γ, IL-6), lowered melatonin and adiponectin levels, downregulated vasoactive intestinal peptide (VIP) type 1 and 2 receptor (VPAC1, VPAC2) expression, and decreased diversity of gut bacteria. EA ameliorated colitis severity and preserved the performance of the epithelial tight junction proteins and VIP receptors, especially VPAC2. Meanwhile, the innate lymphoid cells-derived cytokines in both group 2 (IL-4, IL5, IL-9, IL-13) and group 3 (IL-22, GM-CSF) were elevated in mice colon tissue. Furthermore, dysbiosis was confirmed in the DSS group with and without SF, and EA could maintain the species diversity. Firmicutes could be restored, such as Lachnospiraceae, and Proteobacteria become rebalanced, mainly Enterobacteriaceae, after EA intervention. On the other hand, SF plays different roles in physiological and pathological conditions. In normal mice, interrupted sleep did not affect the expression of claudin-1 and occludin. But VPAC1, VPAC2, and gut microbiota diversity, including Burkholderiaceae and Rhodococcus, were opposite to mice in an inflamed state.

Electroacupuncture and human iPSC-derived small extracellular vesicles regulate the gut microbiota in ischemic stroke via the brain-gut axis

“…The dysfunctional intestinal microflora can stimulate inflammatory response, change the intestinal mucosal permeability, affect the inflammatory factors to aggravate the cerebral ischemia injury, and then feed back to the gut and microflora, and the cycle repeats. Acupuncture and moxibustion can regulate the various links of the cerebral and intestinal axis and block this vicious cycle (62,63).…”

Acupuncture treatment for post-stroke depression: Intestinal microbiota and its role

“…Adiponectin, as a adipocyte derived protein, can inhibit the infiltration of macrophages and the increase of pro-inflammatory cytokines, maintain intestinal homeostasis and improve intestinal barrier integrity ( Obeid et al, 2017 ), and is significantly associated with Firmicutes differential OTUs, which may be a key node between intestinal microbiota and depression ( Bai et al, 2022 ). Liu et al (2020b , 2022) found electroacupuncture restored melatonin and adiponectin levels in plasma to near-normal levels in diseased rats as a result of electroacupuncture, while it could also restore the expression of VIP and its VIP type 1 receptor (VPAC1) and its VIP type 2 receptor (VPAC2). In addition, there is evidence that VIP can improve the immunity of intestinal mucosa ( Seillet et al, 2020 ), and it is also associated with biological depression ( Yu et al, 2021 ; Shukla et al, 2022 ), thus, acupuncture may be a mediator of gut-brain communication.…”

“…In their previous experiment, Liu et al (2020b) discovered that electroacupuncture could inhibit the proinflammatory factors IFN-γ, TNF-α, and IL-6 through TLR4 signaling via MyD88-dependent pathway to prevent excessive immune response in the whole body. According to subsequent related experiments, Liu et al (2022) also found that electroacupuncture could reduce the level of proinflammatory factor IL-6 in plasma, and significantly increase Th2/ILC2 related cytokines (including IL-4, IL-5, IL-9, IL-13, IL-10), as well as increase ILC3-derived cytokines IL-22 and GM-CSF, among which IL-10 is a potent anti-inflammatory cytokine for ILC2s to exert their functions.…”

“…Additionally, Zhang et al (2022d) observed that manual acupuncture significantly reduced the abundance of Firmicutes, Proteobacteria and Escherichia-Shigella in Alzheimer's disease mice, while significantly increasing the abundance of Bacteroides, which led to improvements in intestinal flora. Liu et al (2020bLiu et al ( , 2022 demonstrated that electroacupuncture regulated the overall structure of the intestinal microbiota in the intestinal tract of diseased mice, making the abundance and diversity of Firmicutes is similar to what it is in the healthy mice's intestinal tracts. The mechanism of intestinal microbiota dysbiosis induced by post-stroke depression (PSD) and how acupuncture regulates the intestinal microbiota to treat PSD.…”

Comparison of the Different Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Mice in the Enteric Nervous System

“…Meanwhile, the innate lymphoid cells-derived cytokines (GM-CSF) were elevated in in ammatory mice colon tissue [35].…”