Klebsiella vs. Microbiome Therapy
Klebsiella is one of the more difficult types of overgrowth/infection that we come across in our practice. Not to mention carries the potential to be dangerous, and impact the lives of patients significantly. Klebsiella tend to be opportunistic commensals, that are harmless most of the time, but dangerous when they become overgrown and relocate to other areas of the body. They can survive with or without oxygen, and can utilize citrate, glucose and ammonia within their metabolism, and they produce endotoxins. Most of the time pathogenic strains are picked up in hospitals. This microbe tends to be elevated in atherosclerosis, bipolar CFS, depression, IB, IBS, obesity, Parkinsons Disease, Chronic UTI’s, RA, SIBO, Lupus, UC, T2 Diabetes and Ankylosing Spondylitis. Research has found that elevated Klebsiella can be a causative factor in Ankylosing Spondyltis.
In regards to FMT for treatment of Klebsiella so far there is research only on drug resistant pathogenic strains of Klebsiella. We can refer to Castro et al meta-analysis of ten studies covering 210 patients with Carbapenem resistant Klebsiella treated with FMT.
Meta-Analysis of Fecal Microbiota Transplantation for Carbapenem-Resistant Enterobacteriaceae
In order to participate in most of the trials patients had to have three consecutive positive swabs from either blood, respiratory or rectal secretions which were cultured for Klebsiella and screened for Carbapenem resistant genes.
In one of the reviewed studies, patient age range was 16 to 64, with 48 being the median age. 70% of patients had gut infections, without systemic infection. And 30% had systemic infection. An 84ml frozen enema product was used. No antibiotic preparation was used.
In a second of the reviewed studies, Seventeen patients with a median age of 73 years were treated with FMT for resistant Klebsiella. Patients were reported to have been carrying the Klebsiella for a median of 62.5 days. One week after FMT, 6 of 17 patients were cleared of colonization. After three months, 11 more were cleared of colonization. Six patients still needed and received antibiotics during follow-up. The authors felt that a standardised protocol, including 5 days of antibiotic treatment, bowel cleansing and systematic indwelling devices removal, would improve protocol effectiveness.
In a third of the reviewed trials 39 patients were given a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day). Three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea. 1 patient in this study received FMT via nasogastric tube. The rest received 15 capsules per day for two days. The capsules contained 80% glycerine for stability. The dose administered to patients was derived from a total of about 15–30 g of faecal material from 7 donors. 41% of the intervention group achieved decolonization while 29% of the control group did as well.
Meta-analyzed Cases Results
FMT was reportedly effective to eradicate the Klebsiella in 78% of the total meta-analyzed cases, although the patients who used antibiotics at follow up were included in this as well. Side-effects included constipation and diarrhea. Most of the patients who responded to FMT were improved by the end of one month post FMT, however the rest who did respond to FMT took up to 6-12 months to respond. 30% required at least one top-up.
Case reports such as Ueckermann et al "Fecal Microbial Transplantation for the Treatment of Persistent Multidrug-Resistant Klebsiella pneumoniae Infection in a Critically Ill Patient” tend to focus on critically ill patients with low diversity and low immune function. In this case the patient had experienced multi-organ dysfunction and kidney injury due to the infection. Along with Klebsiella he also tested positive for Candida. 16s rRNA sequencing was used to test his microbiome and diversity, which was low. After the FMT, the patient had no further episodes of sepsis, and blood cultures were repeatedly negative for any bacteria. The patient was successfully discharged from the intensive care unit, and after a period of physical rehabilitation (to address critical illness-associated weakness) returned home in good health. Six weeks post-transplant stool of the patient was analysed, and the Shannon diversity index had improved to 2, considered within the normal range.
I would have loved to see PCR results for all of these patients. What we don’t know is whether patients were still carriers of commensal Klebsiella, and just the antibiotic resistant gene carrying Klebsiella were removed. Or if the total of Klebsiella strains were removed by FMT.
There are ongoing clinical trials on this subject right now. This one for drug resistant Klebsiella Pneumonia for example: https://clinicaltrials.gov/ct2/show/NCT04760665
Other Case Studies..
But, what if you carry Klebsiella without being critically ill (but have a chronic illness) or without knowing whether you carry antibiotic resistant strains of Klebsiella? I have a case study for you. In a client for whom the primary concerns were behavioural and cognitive function. The client completed a herbal antimicrobial and antifungal preparation phase of two weeks. The client received 1.125g of FMT in capsules per 5 days per week for 4 months. And 40ml of enema solution 2 days per week for 4 months. While using FMT the client followed a diverse diet prioritizing prebiotic intake. Client was instructed to avoid sugar alcohols and to supplement HMO’s based on baseline testing.
The motivation to use FMT was not necessarily Klebsiella clearance, however as you’ll see the client was a carrier.
16s rRNA sequencing was done to collect a baseline and follow up sequencing was done in the fourth month. The results are as follows:
Although the other Proteobacteria levels improved with the first round of FMT, as did SCFA composition and beneficial microbe levels improved the status of the Klebsiella did not.
If we read the research done by Ebringer A, Wilson C on Klebsiella’s contribution to autoimmune molecular mimicry, particularly in Ankylosing Spondylitis, we see that Klebsiella metabolizes starch (among other things). A high prebiotic diet that doesn’t remove starch may still promote growth of Klebsiella despite use of antimicrobials and FMT.
At the time of the second test the client’s bowel movements were loose and having 3-4 bowel movements per day.
At this point the approach changed. While continuing FMT use the patient was instructed to implement a lower starch diet. Macro nutrients were shifted to incorporate more fat containing foods relative to carbohydrate and protein. Within two weeks bowel movements solidified and reduced to 1-2x per day.
By the third test Klebsiella was eliminated completely, along with all major Proteobacteria, and the client had experienced improvement in behaviour.
With the shift in diet there was a slight loss in diversity, and an increase in gram negative count, although it still remains in the optimal range. An increase in Bacteroides and Bilophila occurred This is a common shift with diets that are higher in fat. Post FMT the patient implemented a diet with balanced Macros and strategies to reduce the Bacteriodes and Bilophila.
Why These Results Are Critical?
I share these results because I believe that:
The future of FMT use for chronic conditions will be paired with customized nutritional and supplemental support. During FMT patients should receive PCR microbiome testing in order to follow how the colonic microbiome is responding, so that protocols can be adjusted accordingly.
FMT and microbiome centric therapies can help those for whom dysbiosis contributes to their symptoms. Non pathogenic, non drug resistant strains of bacteria may contribute to symptoms of chronic health conditions.
References
[1] Jordán Macareño-Castro, Adán Solano-Salazar, Le Thanh Dong, Md Mohiuddin, J. Luis Espinoza,
Fecal microbiota transplantation for Carbapenem-Resistant Enterobacteriaceae: A systematic review,
Journal of Infection, Volume 84, Issue 6, 2022, Pages 749-759
https://doi.org/10.1016/j.jinf.2022.04.028
[2] Ueckermann V, Hoosien E, De Villiers N, Geldenhuys J. Fecal Microbial Transplantation for the Treatment of Persistent Multidrug-Resistant Klebsiella pneumoniae Infection in a Critically Ill Patient. Case Rep Infect Dis. 2020 Feb 12;2020:8462659. doi: 10.1155/2020/8462659. PMID: 32099702; PMCID: PMC7038171.
