the bacterial population in the colon is extremely large , containing 1014 microbial cells with over 3 million bacterial genes . interestingly , bacteroides , faecalibacterium and bifidobacterium are the most abundant genera , but their relative abundance is highly variable across individuals . bacteria play an essential role in the initiation and perpetuation of gut inflammation in inflammatory bowel disease with evident particularities between crohn disease and ulcerative colitis . it is known that in the ulcerative colitis a dysbiosis is present , an imbalance in the gut microbiota   and it is clear that this imbalance leads to an improper communication between the bacteria and the immune system of the colon mucosa . changing the composition of the intraluminal bacteria induces proinflammatory stimuli , responsible for the characteristic mucosal lesions in ulcerative colitis . recent research shows that dysbiosis in ulcerative colitis is characterized by the decreased concentration of butyrate - producing bacteria such as roseburia hominis and faecalibacterium prausnitzii , both from the ( phylum ) firmicutes division . given these theoretical arguments several studies evaluate the effect of fecal microbiota transplantation in inflammatory bowel disease . the results are contradictory , but it is noted that the positive effects are present , especially in patients with ulcerative colitis [ 68 ] . under these conditions we attempted to evaluate the effect of fecal microbiota transplantation in patients with ulcerative colitis and also to evaluate indications of fecal microbiota transplant in ulcerative colitis , thus answering the question whether fecal microbiota transplantation is a therapeutic alternative or should be reserved only for certain patients . recent research shows that dysbiosis in ulcerative colitis is characterized by the decreased concentration of butyrate - producing bacteria such as roseburia hominis and faecalibacterium prausnitzii , both from the ( phylum ) firmicutes division . given these theoretical arguments several studies evaluate the effect of fecal microbiota transplantation in inflammatory bowel disease . the results are contradictory , but it is noted that the positive effects are present , especially in patients with ulcerative colitis [ 68 ] . under these conditions we attempted to evaluate the effect of fecal microbiota transplantation in patients with ulcerative colitis and also to evaluate indications of fecal microbiota transplant in ulcerative colitis , thus answering the question whether fecal microbiota transplantation is a therapeutic alternative or should be reserved only for certain patients . of 28 patients with fecal microbiota transplantation who tested positive for clostridium difficile ( toxins a and b positive ) and ulcerative colitis in the year 2014 , we selected five patients with ulcerative colitis aged between 26  61 years ; the majority were male with extended colitis or pancolitis and more than 2 years from diagnosis ( table i ) . all patients signed an informed consent and the procedure was approved by the ethics committee of the regional institute of gastroenterology and hepatology , cluj - napoca ( irgh ) . the initiation of fecal microbiota transplant was justified by the response loss to biological therapy in 3 cases , clostridium difficile infection , immunosuppression , or biological therapy refusal ( table ii ) . - 1 patient with ulcerative colitis with low levels of infliximab at 7 weeks from administration in which decreased administration interval had no effect ; - 2 patients with infliximab antibodies ; - 1 female patient with active spurt ( 810 stools / day , blood streaks , abdominal pain ) and superinfection clostridium difficile infection ( a and b positive toxins to patient with ulcerative colitis ) ; - 1 young patient with moderate - severe ulcerative colitis who had refused immunosuppressive and biological treatment . patients and donors were informed about the potential risks and benefits of fecal microbiota transplant and experimental status . donors were selected from the families of patients , first degree relatives who were tested according to the protocol . donor stool screening : ova and parasites , stool culture ( salmonella , shigella , escherichia coli , yersinia enterocolitica , and campylobacter ) , clostridium difficile toxins a and b , giardia antigen . donor serum screening : hiv-1 and hiv-2 , hepatitis a , b , and c , some practitioners additionally screen for : rapid plasma reagin and fluorescent treponema antibody - absorbed treponema pallidum . additional potential exclusions should include donors with a history of incarceration , tattoo or body piercing in the past 6 months , current or known exposure to a communicable disease , use of immunosuppressant agents , or antibiotics within the last 3 months . travel within the past 6 months to an area known to be a risk factor for diarrheal illness or other infectious diseases should also be considered in the analysis of donors . fecal suspension ( ~ 150 ml ) was diluted in 0.9 % sterile saline solution up to a volume of 400425 ml . subsequently the suspension was filtered several times . donated stool is mixed with diluent to a consistency that can be injected via the biopsy channel of a colonoscopy . before aspiration into a syringe , the administration method was transcolonic during colonoscopy , after standard preparation ( fortrans split - in doses that varied according to each patient s bowel transit ) . colonoscopy offers the advantage of allowing direct colonic mucosa and evaluation , assessment of disease severity and exclusion of coexisting pathological conditions . the patients received 4 mg of loperamide in order to reduce gut motility immediately after fecal microbiota transplant and 6 hours after the procedure . serological tests were evaluated every day . the day after the fecal microbiota transplant the patients were discharged . clinical remission : disappearance of symptoms ( pain , abdominal discomfort ) , the decrease in the number of stools , stool normalization , the disappearance of pathological products in the stool ( mucus , blood ) ; biological remission : erythrocyte sedimentation rate , white blood cell , c - reactive protein ; endoscopic remission : mayo score reduction ( of at least 3 points ) or mucosal healing installation . of 28 patients with fecal microbiota transplantation who tested positive for clostridium difficile ( toxins a and b positive ) and ulcerative colitis in the year 2014 , we selected five patients with ulcerative colitis aged between 26  61 years ; the majority were male with extended colitis or pancolitis and more than 2 years from diagnosis ( table i ) . all patients signed an informed consent and the procedure was approved by the ethics committee of the regional institute of gastroenterology and hepatology , cluj - napoca ( irgh ) . the initiation of fecal microbiota transplant was justified by the response loss to biological therapy in 3 cases , clostridium difficile infection , immunosuppression , or biological therapy refusal ( table ii ) . - 1 patient with ulcerative colitis with low levels of infliximab at 7 weeks from administration in which decreased administration interval had no effect ; - 2 patients with infliximab antibodies ; - 1 female patient with active spurt ( 810 stools / day , blood streaks , abdominal pain ) and superinfection clostridium difficile infection ( a and b positive toxins to patient with ulcerative colitis ) ; - 1 young patient with moderate - severe ulcerative colitis who had refused immunosuppressive and biological treatment . patients and donors were informed about the potential risks and benefits of fecal microbiota transplant and experimental status . donors were selected from the families of patients , first degree relatives who were tested according to the protocol . donor stool screening : ova and parasites , stool culture ( salmonella , shigella , escherichia coli , yersinia enterocolitica , and campylobacter ) , clostridium difficile toxins a and b , giardia antigen . donor serum screening : hiv-1 and hiv-2 , hepatitis a , b , and c , some practitioners additionally screen for : rapid plasma reagin and fluorescent treponema antibody - absorbed treponema pallidum . additional potential exclusions should include donors with a history of incarceration , tattoo or body piercing in the past 6 months , current or known exposure to a communicable disease , use of immunosuppressant agents , or antibiotics within the last 3 months . travel within the past 6 months to an area known to be a risk factor for diarrheal illness or other infectious diseases should also be considered in the analysis of donors . fecal suspension ( ~ 150 ml ) was diluted in 0.9 % sterile saline solution up to a volume of 400425 ml . subsequently the suspension was filtered several times . donated stool is mixed with diluent to a consistency that can be injected via the biopsy channel of a colonoscopy . before aspiration into a syringe , the suspension is filtered through gauze pads or strainer to remove large particulate matter . the administration method was transcolonic during colonoscopy , after standard preparation ( fortrans split - in doses that varied according to each patient s bowel transit ) . colonoscopy offers the advantage of allowing direct colonic mucosa and evaluation , assessment of disease severity and exclusion of coexisting pathological conditions . the patients received 4 mg of loperamide in order to reduce gut motility immediately after fecal microbiota transplant and 6 hours after the procedure . serological tests were evaluated every day . the day after the fecal microbiota transplant the patients were discharged . clinical remission : disappearance of symptoms ( pain , abdominal discomfort ) , the decrease in the number of stools , stool normalization , the disappearance of pathological products in the stool ( mucus , blood ) ; biological remission : erythrocyte sedimentation rate , white blood cell , c - reactive protein ; endoscopic remission : mayo score reduction ( of at least 3 points ) or mucosal healing installation . mild to moderate abdominal pain was observed in the first 2 hours after transplantation , but did not require any medication . one patient presented mild rectal bleeding , for this reason two months after fecal microbiota transplantation the decision to reintroduce azathioprine treatment was taken . for 2 patients the 5 acetyl salicylic acid dose patients 1 and 3 were free of ulcerations , mucosal healing was found in patients 2 and 5 ( table iii ) . we watched using the t test and significance of c - reactive protein value before and after fecal microbiota transplant ( table iv ) . cases 2 , 4 and 5 had a sustained therapeutic effect , clinical and biological remission was maintained even after 1 year from fecal microbiota transplant . biologic therapy was reintroduced ( infliximab ) with favorable outcome administered at 810 weeks interval depending on colonic transit ( the patient decided the optimal administration interval ) . case 3 had an incomplete remission ( 23 stools / day , blood streaks present sometimes in the stool ) , for this reason azathioprine was reintroduced . one year after fecal microbiota transplant , under azathioprine , the patient presented 2 stools / day , without blood streaks . cases 2 , 4 and 5 had a sustained therapeutic effect , clinical and biological remission was maintained even after 1 year from fecal microbiota transplant . biologic therapy was reintroduced ( infliximab ) with favorable outcome administered at 810 weeks interval depending on colonic transit ( the patient decided the optimal administration interval ) . case 3 had an incomplete remission ( 23 stools / day , blood streaks present sometimes in the stool ) , for this reason azathioprine was reintroduced . one year after fecal microbiota transplant , under azathioprine , the patient presented 2 stools / day , without blood streaks . current therapeutic methods achieve control in most cases . the appearance of biological therapy has achieved deep remission and mucosal healing in a significant number of cases . however , there are patients in which biological therapy is not effective and particularly the loss of therapeutic effect in a significant percentage of patients after a variable period of time has been described . loss effect is due to either low levels of infliximab , or the appearance of antibodies against the biological treatment . the remedy is to increase the dose , shorten the dosing intervals or treatment change ( adalimumab after infliximab ) . fecal microbiota transplant has a theoretical justification in ulcerative colitis . in these conditions we tested the efficiency of fecal microbiota transplantation in 3 patients who had lost the therapeutic effect due to insufficient dose ( 1 patient ) or antibody development ( 2 patients ) . patients entered clinical remission immediately , remission was maintained in one case until the writing of this article and for two other cases for 1012 months . the reintroduction of biological treatment or azathioprine for the 2 cases mentioned above proved to have a profound effect on maintaining remission duration and treatment effect was regained . our results show that fecal microbiota transplantation may be considered as a necessary rescue therapy in the loss of therapeutic effect for biological therapy . of course there is also the possibility to switch to another biological treatment with durable results but only after a period of several wash - out weeks , in our patients we could not afford to lose the time as patients were in a prolonged acute spurt . a number of cases have been published in china , where clinical remission in 70% of patients achieved long term remission . the female patient with clostridium difficile superinfection had a moderate - severe activity spurt with 8 stools / day and long term biological parameters ( erythrocyte sedimentation rate and c - reactive protein ) severely altered . the superinfection of the clostridium difficile infection had occurred during the active spurt for which biological therapy was programmed . after fecal microbiota transplant treatment pathological stools disappeared within the next day and complete remission was maintained for 5 months . for clostridium difficile infection it is very well known that fecal microbiota transplantation is an effective therapy   and its association with the spurt activity can be considered the indication of choice for fecal microbiota transplantation , although results in literature are contradictory ( positive results or ulcerative colitis reactivation ) . the 5 patient was a 26 year old male who had colitis and multiple moderate spurts . the results were excellent and the patient has been in complete remission for more than 2 years . in this case fecal microbiota transplant was a therapeutic alternative that could be considered in young patients who refuse aggressive treatments : immunosuppression or biological therapy . although encouraging our results were obtained on a small number of cases . but this diversity can provide an insight into the main indications of fecal microbiota transplantation in ulcerative colitis . we identified several cases in which it can be used : the loss of therapeutic effect for biological medication through under dosing or the appearance of antibodies may be an indication for salvage therapy using fecal microbiota transplant . in these cases when the fecal microbiota transplant effect diminished we discovered that biological and immunosuppressive therapy response was achieved again . fecal microbiota transplant is the choice when superinfection of the clostridium difficile infection is present . finally , for patients , especially young patients who refuse aggressive treatments , fecal microbiota transplantation can be considered as a therapeutic alternative .
background and aimsfecal microbiota transplantation is used with success in persistent ( more than two episodes ) clostridium difficile infection ; it has also gained importance and started to be used in inflammatory bowel disease . 
 there are theoretical arguments that justify its use in ulcerative colitis or crohn s disease . based on our clinical cases we tried to evaluate the indications of fecal microbiota transplantation young patients with ulcerative colitis and multiple relapses , in which biological or immunosuppressive treatment were ineffective.methodsfive patients with moderate - severe ulcerative colitis or clostridium difficile infection who ceased to have a therapeutic response to biological therapy , 
 were given fecal microbiota transplant as an alternative to biological therapy and/or immunosuppression . 
 fecal microbiota transplant was administered via colonoscopy using healthy donors from their family.resultsthe results were favorable and spectacular in all patients and complete remission was achieved for at least 10 months . 
 clinical remission was achieved in all patients . 
 endoscopic appearance of ulcers in patients improved . in 2 patients 
 the effect of the fecal microbiota transplant diminished after 1012 months and the tendency to relapse appeared ( 34 stools / day , blood streaks present sometimes in the stool ) . 
 reintroduction of systemic therapy or immunosuppression demonstrated that patients regained the therapeutic response to these treatments , and remission was maintained.conclusionfecal microbiota transplantation can be used as salvage therapy in patients refractory to biological therapy , as elective therapy in clostridium difficile infection or as an alternative therapy in young patients with multiple relapses who have reservations regarding biological or immunosuppressive treatment .