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. 2025 Feb 17;28(4):112053.
doi: 10.1016/j.isci.2025.112053. eCollection 2025 Apr 18.

Improved oxygen saturation and acclimatization with bacteriotherapy at high altitude

Affiliations

Improved oxygen saturation and acclimatization with bacteriotherapy at high altitude

James J Yu et al. iScience. .

Abstract

High altitude imposes physiological stress on the human body due to reduced oxygen availability, and options to improve acclimatization are limited. Seventeen participants underwent a randomized, doubled-blinded, placebo-controlled study to test the effects of a multi-strain probiotic on acclimatization to high altitude (3,800 m). The primary outcome was oxygen saturation (SpO2) during both daytime and nighttime. Secondary measurements included acute mountain sickness (AMS) score, sleep measurements, ventilation, resting heart rate, blood pressure, heart rate variability, and fasting glucose levels. The probiotic group exhibited a higher daytime and nighttime SpO2 compared to the placebo group at high altitude. The probiotic group also exhibited a lower AMS score and enhanced acclimatization relative to the placebo group at high altitude, evidenced by higher SpO2 and lower AMS scores in treatment versus placebo groups. These results suggest bacteriotherapy as a novel, non-invasive intervention for high-altitude acclimatization.

Keywords: Environmental health; Pharmacology.

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Conflict of interest statement

T.S.S. and A.M. are funded by the National Institutes of Health. A.M. reports income from Eli Lilly, Zoll, Powell Mansfield, and Livanova. ResMed provided a philanthropic donation to UC San Diego.

Figures

None
Graphical abstract
Figure 1
Figure 1
Individuals in the probiotic group had increased SpO2 at high altitude during both daytime and nighttime compared to the placebo group (A) All individuals experienced a decrease in SpO2 upon ascent to high altitude (p < 0.0001, paired Student’s t test). A two-way ANOVA revealed a significant effect of treatment group (p < 0.0001) but not time point (p = 0.47) on daytime SpO2 at high altitude, and a Bonferroni post hoc revealed a mean increase of 3.6% in the probiotic group. Error bars represent standard error (SE). (B) A two-way ANOVA also revealed a significant effect of treatment group (p = 0.011) but not time point (p = 0.66) on mean nocturnal SpO2 at high altitude, and a Bonferroni post hoc revealed a mean increase of 5.1% in the probiotic group. All 17 individuals had at least one night of sleep data at high altitude and nine individuals (five probiotic, four placebo) had three nights of sleep data at high altitude. Error bars represent SE.
Figure 2
Figure 2
The probiotic group had decreased acute mountain sickness scores compared to the placebo group during the first two days at high altitude All individuals had an AMS score of two or less at sea level. The placebo group experienced a significant increase in AMS scores from sea level to the first day at high altitude (p = 0.0022, paired Student’s t test), while the probiotic group did not (p = 0.10, paired Student’s t test). The probiotic group had a lower AMS score during the first two days at high altitude compared to the placebo group (p = 0.0026, two-way ANOVA with Bonferroni post hoc) with a mean decrease of 2.5. Error bars represent SE.
Figure 3
Figure 3
The probiotic group exhibited higher Vi during acute hypoxia exposure and higher hypercapnic HVRs at high altitude compared to the placebo group (A–D) The probiotic group (A) exhibited a higher Vi during acute hypoxia at high altitude compared to the placebo group (p = 0.012, unpaired t test) but (B) did not have a significantly higher HVR at high altitude (p = 0.062, unpaired t test). There were no significant differences between the treatment groups for (C) Vi during acute hypercapnia (p = 0.054, unpaired t test) and (D) HCVR at high altitude (p = 0.22, unpaired t test). (E) The probiotic group exhibited a higher Vi during combined hypercapnia-hypoxia (p = 0.002, unpaired t test) compared to the placebo group and both groups exhibited a higher Vi in combined hypercapnia-hypoxia compared to just hypoxia (depicted in faded images). (F) The probiotic group also exhibited a higher hypercapnic HVR at high altitude compared to the placebo group (p = 0.036, unpaired t test). One asterisk (∗) represents p < 0.05 and two asterisks (∗∗) represents p < 0.01. All error bars represent SE.
Figure 4
Figure 4
Treatment groups did not exhibit any differences in AHI or ODI at high altitude Both treatment groups experienced an increase in (A) AHI (p = 0.0078 for placebo group, p = 0.0012 for probiotic group, paired Student’s t tests) and (B) ODI (p = 0.00096 for placebo group, p = 0.00089 for probiotic group, paired Student’s t tests. There was no difference in (A) AHI or (B) ODI between the two groups at high altitude. Error bars represent SE.
Figure 5
Figure 5
Treatment groups did not exhibit any differences in resting heart rate, systolic blood pressure, nor diastolic blood pressure at high altitude (A) Both groups experienced an increase in resting HR from sea level to high altitude (p = 0.0084 for placebo group, p = 0.0064 for probiotic group, Student’s t test) but did not differ in resting HR at high altitude. Error bars represent SE. (B) There was no difference in systolic blood pressure from sea level to high altitude in either group and no difference in systolic blood pressure between the two groups at high altitude. (C) Diastolic blood pressure decreased with exposure to high altitude in the placebo group (p = 0.045, Student’s paired t test) but did not change in the probiotic group. There was no difference in diastolic blood pressure between treatment groups at high altitude. Error bars represent SE.
Figure 6
Figure 6
Treatment groups did not exhibit differences in measures of heart rate variability during exposure to high altitude (A) Both groups experienced a decrease in SDRR during the second day at high altitude compared to sea level (p = 0.028, Student’s t test) but no differences between treatment groups (p = 0.21, two-way ANOVA). (B) Neither group exhibited a change in RMSDD with exposure to high altitude (p = 0.074, Student’s t test) nor was there a difference between treatment groups in RMSDD (p = 0.10, two-way ANOVA). (C and D) There were no differences in LF or HF between sea level and the second day at high altitude in both groups (p = 0.081 and p = 0.155, respectively, Student’s t test) and no differences between groups at high altitude for both LF (p = 0.20, two-way ANOVA) and HF (p = 0.20, two-way ANOVA). (E) Both groups experienced an increase in LF/HR ratio during the second day at high altitude compared to sea level (p = 0.03, Student’s t test) but no differences between treatment groups (p = 0.12, two-way ANOVA). All error bars represent SE.
Figure 7
Figure 7
Treatment groups did not exhibit differences in fasted glucose at high altitude Both treatment groups did not experience a significant change in fasted glucose from sea level to the first morning (Day 2) at high altitude and did not differ in fasted glucose levels at high altitude. Error bars represent SE.

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