The Composition And Medication Modification Of Intestinal Flora Of Bedridden Stroke Patients

Background:Stroke is a major public health concern with high rates of morbidity and mortality worldwide.Long-term bed is a common outcome after stroke.Bedridden stroke patients,are liable to a wide range of complications resulted in low quality of life.Due to diet,activity and mental factors,constipation,diarrhea and other intestinal dysfunctions are among the prominent complications.Meanwhile intestinal disorder acts as a risk factor for the treatment and prognosis.The mechanism of constipation in bedridden stroke patients remains unclear,constipation is often caused by intestinal dysfunction.Healthy intestinal flora is vital for prevention of constipation and other intestinal dysfunctions.The interaction between intestinal flora and its host is called intestinal micro-ecology(Gut microflora),which is the largest micro-ecological system in human body.Due to its importance in human health and disease,gut microflora has become a research hotspot in recent years.Through microbial-intestinal-cerebral axis in vivo,intestinal flora act on human nervous system and play a key role to the CNS(central nervous system,CNS)Disease.There are several mechanism possible,intestinal flora stimulate the intestinal immune system to secret immune or inflammatory factors which could directly activate the brain or the hypothalamus-pituitary-adrenal axis;participating in tryptophan metabolism,intestinal flora affects the content of serotonin in human body;in addition,some intestinal flora synthesizes and secrete certain neurotransmitters or neurotrophic factors for nervous system.Current study has included the multiple sclerosis(multiple sclerosis,MS),Parkinson’s disease(Parkinson disease,PD),Alzheimer’s disease(Alzheimer’ s disease,AD)and Stroke.The development of next generation sequencing and bio-information technology promote meta genomics research.Meta genomics either clone the total DNA,construct meta-genomic library to discover de novo microbiomes;or sequence 16s rDNA amplicon to systematic analysis the genetic diversity and molecular ecological information of microorganisms.It explains the relationship between microbial community diversity,evolutionary relationship,population structure,functional activity and environment,and greatly expands the scope of microbiology Research.The development of intestinal meta genomics profound and deepen the study of intestinal flora.As a new biological product,probiotics has been attracting more and more attention in the medical pharmaceutical industry and has been the auxiliary and even alternative treatment for many diseases.It has been reported that its main function can be "protection,immunity,antibacterial,balance,nutrition,anti-tumor,protect liver,reduce blood lipid and etc".At present,its clinical application mainly involves the following aspects,diarrhea,functional constipation,liver disease,colon cancer.The functional mechanism of probiotics remains unclear at present but balancing and restoring intestinal flora is of great significance to the health and treatment of disease.Objective:First,to study the distinct composition of intestinal flora in bedridden stroke patients comparing to healthy oldie.Second,measure the effects of probiotics on balancing intestinal flora and eliminating constipation and diarrhea.Third,to associate probiotics,intestinal flora with nervous system function.Methods:Since September 2017 to August.2018,40 bedridden post-stroke patients were recruited and randomly divided into probiotics untreated group(non-probiotics treatment,NPT)and probiotics treatment group(probiotic treatment,PT),and 20 healthy oldies were enlisted as control group(health control,HC).NPT group was routinely given post-stroke treatment,and PT group was administered Clostridium butyricum Capsule orally(3 tablets bid).NPT group was routinely given post-stroke treatment,and PT group was administered Clostridium butyricum Capsule orally(3 tablets bid).The difference changes of the intestinal tract symptoms within three groups were recorded.Fecal specimens were collected 8 weeks after treatment.DNA was extracted,used to generate DNA amplicons of the V4 hypervariable region of the bacterial 16S rDNA gene,and subjected to Illumina(MiSeq2500/4000)sequencing.At the same time,NIHSS score was applied to evaluate the neurological function of stroke patients.Results:1.Clostridium butyricum Capsules significantly reduced the incidence of constipation in PT group comparing to NT group(10%vs 40%,p<0.05)。2.0n average,over 61348 tags per sample were generated.High bacterial diversity was noted in the fecal of PT patients comparing to NT patients and HC oldies[242.4 operational taxonomical units(OTU)vs 128 OTU vs 150.25 OUT at 3%divergence)with no significant difference.3.A total of 9,11 and 10 predominant phyla(relative abundance>0.01%)were presented in HC,NT and PT groups respectively.The first five phyla were Bacteroidetes,Firmicutes,Actinobacteria,Fusobacteria,Proteobacteria for HC oldies;Firmicutes,Bacteroidetes,Proteobacteria,Actinobacteria,and Euryarchaeota for NT patients;Bacteroidetes,Firmicutes,Proteobacteria,Verrucomicrobia,Actinobacteria,and Fusobacteria for PT patients.Clostridium butyricum Capsules restored the population of Proteobacteria and Bacteroidetes in PT patients to that of HC oldies.The relative abundance of Proteobacteria is 3%,20%,and 7%in HC,NT,and PT groups respectively.43%,30%,and 58%are the ex facto of Bacteroidetes.4.A total of 21 genera with>1%relative abundance was screened,the first 5 were:Bacteroides(bacillus 25.2%),Parabacteroides(8.7%)Alistipes(7.5%),Escherichia(Escherichia coli 6.7%),Clostridium_xlva(3.3%),The first five genera accounted for 51.4%of the total composition of intestinal flora.Compared to HC patients,NPT patients have significantly decreased abundance of Bifidobacterium,Lactobacillus,and Faecalibacterium,while increased abundance of Bbacteroides,Enterococcus,Escherichia,and Alistipes.Compared to NPT patients,PT patients’Bifidobacterium,Lactobacillus,Faecalibacterium,and Escherichia abundance significantly increased;whereas reduced the Bacteroides,and Enterococcus.5.Compared to HC oldies,NPT patients’ Alistipes population improved,while Faecalibacterium declined.Conclusion:Distinct changes in the population of intestinal flora occur in patients with post-stroke bedridden.Probiotics have the effects on restoring the intestinal flora and preventing constipation.