The Study Of Alleviation Effects On Cathartic Colon By Lactic Acid Bacteria

Cathartic colon is the intestinal dysfunction caused by long-term use of stimulating laxatives such as senna,rhubarb,aloe vera,and buckthorn.Intractable constipation is the main clinical manifestation.Once cathartic colon occurs,most of the ordinary laxatives will lose their effect.Compared with ordinary constipation,the most prominent feature of patients with cathartic colon is the presence of severe enteric nerve damage and intestinal mucosal lesions.So,except for constipation,the treatment also needs to repair the enteric nerve and intestinal barrier.Current studies have shown that lactic acid bacteria such as Bifidobacterium and Lactobacillus have outstanding effects in alleviating constipation,and also show potential in repairing the intestinal barrier and treating neurodegenerative diseases.Therefore,it was believed that lactic acid bacteria have potential advantages in alleviating the cathartic colon.In this study,a mouse model of cathartic colon caused by long-term use of senna was established.Lactic acid bacteria were used for the treatment of cathartic colon for the first time,aiming to evaluate the repair effects on the enteric nerve and intestinal barrier by lactic acid bacteria,also explore the possible pathways to relieve the cathartic colon.It was looked forward that this study would provide a safe and effective probiotic therapy for not only constipation alleviation,but also the intestinal nerves repair.The main results of this article are as follows:First,a cathartic colon mouse model by long-term use of senna leaf extract was established to evaluate the alleviation effect of lactic acid bacteria,including 10 strains of Bifidobacterium and 10 strains of Lactobacillus.Among these 10 strains,4 strains(Bifidobacterium adolescentis BA2,B.bifidum BB1,B.bifidum BB2,Lactobacillus paracasei LP1)were screened which can effectively relieve the cathartic colon.Secondly,the effects of lactic acid bacteria on the enteric nerve were evaluated by the levels of enteric glial cells(EGCs),neurotrophic factors,neurotransmitters and Interstitial cells of Cajal(ICC)in the colon.The effects on the intestinal barrier of cathartic colon mice by lactic acid bacteria were evaluated by measuring the levels of tight junction proteins,mucins,inflammation in the colon and the number of stem cells(ISCs).The results show that lactic acid bacteria can repair enteric nerve and barrier function by increasing the number of EGCs,ICC and ISCs in colon.It is speculated that lactic acid bacteria can repair enteric nerves by activating EGCs to promote neural proliferation and differentiation,and restore intestinal barrier by stimulating the proliferation and differentiation of ISCs.Different lactic acid bacteria strains showed different ways of effect on cathartic colon alleviation.ISCs contribute to the alleviation of B.bifidum BB1 and BB2 while EGCs stimulated by increasing SCFAs may be the main pathway of alleviation by L.paracasei,and both of the above effects were observed in the alleviation by B.adolescentis.Finally,to further explore the relationship between the changes in the intestinal environment and the alleviation pathways used by lactic acid bacteria,the content of short chain fatty acids(SCFAs)in the cecum content of mice and the species abundance were measured.It was found that the SCFAs levels in the contents of the cecum of mice was significantly increased after gavage of lactic acid bacteria.Among them,the content of acetate acid and isovaleric acid was related to the number of neurons and EGCs.It is speculated that the increase of acetate acid and isovaleric acid stimulates the proliferation of EGCs.On the one hand,the increase of EGCs was directly involved in regulating intestinal movement,and on the other hand,it played a role in supporting and protecting neurons,rebuilding intestinal homeostasis,and alleviating the cathartic colon.With the evaluation of the gut microbiota diversity by ?-diversity index,?-diversity index and the species abundance,it was found that the cathartic colon mice showed obvious gut microbiota dysbiosis,which is manifested by the decrease of intestinal ?-diversity.The abundance of beneficial bacteria such as Akkermansia,Ruminococcaceae?UCG?014,Lachnospiraceae?UCG?006,Bifidobacterium,Faebacterium,and [Eubacterium] xylanophilum group,and the abundance of Odoribacter was significantly increased.Lactic acid bacteria intervention can significantly adjust the gut microbiota of cathartic colon mice.B.adolescentis BA2 significantly increases the abundance of Akkermansia and Bacteroides,and reduces the abundance of Odoribacter;B.bifidum BB1 significantly increased the abundance of Akkermansia,Bifidobacterium,Lactobacillus,[Eubacterium] xylanophilum group,and reduced the abundance of Odoribacter,;B.bifidum BB2 significantly increased the abundance of Bifidobacterium,Faecalibacterium,and Bacteroides;L.paracasei LP1 can significantly increase the abundance of the beneficial bacteria Ruminococcaceae UCG-014,Bifidobacterium,and Lactobacillus.In summary,lactic acid bacteria can be used to relieve the cathartic colon,also can repair the intestinal nerve damage and intestinal barrier damage caused by long-term use of laxative stimulation,improve the intestinal environment,and rebuild intestinal homeostasis.Among the lactic acid bacteria strians that effectively relieve the cathartic colon,different species of bacteria show different pathways.ISCs contribute to B.bifidum to relieve the cathartic colon while EGCs stimulated by increasing SCFAs may be the main pathway in alleviation by L.paracasei,and both of the above effects are observed in the alleviation of B.adolescentis.