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other·critical care, gastroenterology, microbiome, nutrition, clinical trial·PMC10880344

Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults

BMC Medicine · 16 authors, 12 centres

AI SUMMARY

FIDELITY 100%

POPULATIONCritically ill adults (n=54) with intact gastrointestinal tract, admitted to ICU, mean age 64.6 years, 39% female, 87% on antibiotics

INTERVENTIONOral or nasogastric kefir (Lifeway Foods) in escalating doses: 60 mL, then 120 mL after 12 h, then 240 mL daily

COMPARISONNo control group (open-label single-arm study); within-patient comparison of stool samples at two timepoints (T1 within 72 h of admission, T2 ≥72 h after full dose)

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TL;DR

This phase I trial in 54 ICU patients found that kefir administration is safe and feasible, with 91% of prescribed doses successfully given and no kefir-related bacteremia. Although gut microbial diversity did not increase, the Gut Microbiome Wellness Index (GMWI) significantly improved (P=0.034), suggesting potential gut health benefits. These findings support larger trials of kefir to mitigate ICU-associated gut dysbiosis.

Full summary

3,066 CHARS

**Background:** Gut microbiome dysbiosis is common in ICU patients and is associated with increased risk of nosocomial infections, organ failure, and mortality. Standard ICU therapies (antibiotics, acid suppression, opioids) further disrupt the microbiome. Probiotic supplements have not consistently improved microbial diversity, but fermented foods like kefir may offer benefits. This study aimed to evaluate the safety, feasibility, and gut microbiome impact of kefir in critically ill adults.

**Methods:** This open-label phase I trial enrolled 54 critically ill patients (mean age 64.6 years, 39% female, 87% on antibiotics) with functional GI tracts. Kefir (Lifeway Foods, 25–30 billion CFU per 240 mL serving) was administered in an ascending dose schedule: 60 mL initially, then 120 mL after 12 h, then 240 mL daily. Safety was monitored for bloating, vomiting, aspiration, diarrhea, bacteremia, or fungemia. Feasibility was defined as delivery of >75% of prescribed doses. Stool samples were collected within 72 h of ICU admission (T1, n=29) and ≥72 h after full-dose kefir (T2, n=13). Shotgun metagenomic sequencing was performed, and taxonomic profiling used MetaPhlAn3. α-diversity (Shannon Index, richness) and β-diversity (Bray-Curtis, PERMANOVA) were assessed. The Gut Microbiome Wellness Index (GMWI) was calculated based on 42 health-associated species.

**Key Results:** Of 393 prescribed kefir doses, 359 (91%) were successfully administered. No kefir-related bacteremia, fungemia, or deaths occurred. Two patients developed diarrhea while on laxatives and tube feeds; no other GI side effects were attributed to kefir. Four patients dropped out (one due to bloating from undiagnosed mesenteric ischemia, three due to taste). In the 13 patients with paired stool samples, α-diversity significantly decreased from T1 to T2 (Shannon Index P=0.048; species richness P=0.010). PERMANOVA showed timepoint accounted for 6% of variance in community composition (P=0.004). GMWI significantly increased from T1 to T2 (P=0.034, one-sided Wilcoxon). Among 12 kefir microbial species, three Lactobacillus species (L. plantarum, L. reuteri, L. rhamnosus) showed increased prevalence at T2, while Bifidobacterium longum decreased; seven species were never detected. Of 23 GMWI species observed, two health-scarce species (Hungatella hathewayi and Clostridium bolteae) significantly decreased at T2 (P<0.05, permutation test).

**Clinical Implications:** This first-in-ICU study demonstrates that kefir can be safely and feasibly administered to critically ill patients with intact GI tracts. Despite ongoing antibiotic therapy and declining microbial diversity, kefir was associated with improved GMWI and engraftment of some beneficial Lactobacillus species. The findings support larger randomized controlled trials to evaluate kefir's efficacy in mitigating ICU-associated dysbiosis and potentially reducing nosocomial infections. Limitations include the single-arm design, small sample size for microbiome analysis, and inability to control for antibiotics.

PICO

PPOPULATION

Critically ill adults (n=54) with intact gastrointestinal tract, admitted to ICU, mean age 64.6 years, 39% female, 87% on antibiotics

IINTERVENTION

Oral or nasogastric kefir (Lifeway Foods) in escalating doses: 60 mL, then 120 mL after 12 h, then 240 mL daily

OOUTCOME

Safety (adverse events, bacteremia), feasibility (≥75% of doses administered), gut microbiome changes (α-diversity, β-diversity, GMWI, engraftment of kefir species)

STUDY TYPE

other

SPECIALTY

critical care

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10880344

Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults

BMC Medicine

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ABSTRACT

Abstract Background Dysbiosis of the gut microbiome is frequent in the intensive care unit (ICU), potentially leading to a heightened risk of nosocomial infections. Enhancing the gut microbiome has been proposed as a strategic approach to mitigate potential adverse outcomes. While prior research on select probiotic supplements has not successfully shown to improve gut microbial diversity, fermented foods offer a promising alternative. In this open-label phase I safety and feasibility study, we examined the safety and feasibility of kefir as an initial step towards utilizing fermented foods to mitigate gut dysbiosis in critically ill patients. Methods We administered kefir in escalating doses (60 mL, followed by 120 mL after 12 h, then 240 mL daily) to 54 critically ill patients with an intact gastrointestinal tract. To evaluate kefir’s safety, we monitored for gastrointestinal symptoms. Feasibility was determined by whether patients received a minimum of 75% of their assigned kefir doses. To assess changes in the gut microbiome composition following kefir administration, we collected two stool samples from 13 patients: one within 72 h of admission to the ICU and another at least 72 h after the first stool sample. Results After administering kefir, none of the 54 critically ill patients exhibited signs of kefir-related bacteremia. No side effects like bloating, vomiting, or aspiration were noted, except for diarrhea in two patients concurrently on laxatives. Out of the 393 kefir doses prescribed for all participants, 359 (91%) were successfully administered. We were able to collect an initial stool sample from 29 (54%) patients and a follow-up sample from 13 (24%) patients. Analysis of the 26 paired samples revealed no increase in gut microbial α-diversity between the two timepoints. However, there was a significant improvement in the Gut Microbiome Wellness Index (GMWI) by the second timepoint ( P = 0.034, one-sided Wilcoxon signed-rank test); this finding supports our hypothesis that kefir administration can improve gut health in critically ill patients. Additionally, the known microbial species in kefir were found to exhibit varying levels of engraftment in patients’ guts. Conclusions Providing kefir to critically ill individuals is safe and feasible. Our findings warrant a larger evaluation of kefir’s safety, tolerability, and impact on gut microbiome dysbiosis in patients admitted to the ICU. Trial registration NCT05416814 ; trial registered on June 13, 2022. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-024-03299-x. Keywords: Kefir, ICU, Critical illness, Probiotics, Gut microbiome, GMWI

CITATION EXPORT

Vinod K Gupta, Sanu Rajendraprasad, Mahmut Ozkan et al.. Safety, feasibility, and impact on the gut microbiome of kefir administration in critically ill adults. BMC Medicine. (2024). https://doi.org/10.1186/s12916-024-03299-x

AUTHORS

16 · 12 CENTRES

Vinod K Gupta, Sanu Rajendraprasad, Mahmut Ozkan, Dhanya Ramachandran, Sumera Ahmad, Johan S Bakken, Krzysztof Laudanski, Ognjen Gajic, Brent Bauer, Simon Zec, David W Freeman, Sahil Khanna, Aditya Shah, Joseph H Skalski, Jaeyun Sung, Lioudmila V Karnatovskaia

1Microbiome Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN USA
2Division of Surgery Research, Department of Surgery, Mayo Clinic, Rochester, MN USA
3Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN USA
4Department of Surgery, Mayo Clinic, Rochester, MN USA
5Section of Infectious Diseases, St Luke’s Hospital, Duluth, MN USA
6Department of Anesthesiology and Perioperative Care, Mayo Clinic, Rochester, MN USA
7Department of Internal Medicine, Mayo Clinic, Rochester, MN USA
8Department of Anesthesiology and Perioperative Care, Beth Israel Deaconess Medical Center, Boston, MA USA
9Department of Neurologic Surgery, Mayo Clinic, Jacksonville, FL USA
10Division of Gastroenterology, Department of Medicine, Mayo Clinic, Rochester, MN USA
11Division of Public Health, Infectious Diseases, and Occupational Medicine, Department of Medicine, Mayo Clinic, Rochester, MN USA
12Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN USA