Human gut microbiota adaptation to high-altitude exposure: longitudinal analysis over acute and prolonged periods

From BugSigDB
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Ma X, Duan C, Wang X, Tao Y, Yang L, Teng Y, Pan Y, Zhang M, Xu J, Sheng J, Wang X, Jin P
Journal
Microbiology spectrum
Year
2025
Keywords:
16S rDNA, dysbacteriosis, gut microbiota, high altitude, longitudinal effects
UNLABELLED: This study investigated the longitudinal effects of acute (7-day) and prolonged (3-month) high-altitude exposure on gut microbiota in healthy adult males, addressing the limited data available in human populations. A cohort of 406 healthy adult males was followed, and fecal samples were collected at three time points: baseline at 800 m (406 samples), 7 days after ascending to 4,500 m (406 samples), and 2 weeks post-return to 800 m following 3 months at high altitude (186 samples). High-throughput 16S ribosomal DNA sequencing was employed to analyze microbiota composition and diversity. Results revealed significant changes in alpha- and beta-diversity, with acute high-altitude exposure inducing more pronounced effects compared to prolonged exposure. Specifically, acute exposure increased opportunistic pathogens (Ruminococcus and Oscillibacter) but decreased beneficial short-chain fatty acid producers (Faecalibacterium and Bifidobacterium). Notably, these changes in microbiota persisted even after returning to low altitude, indicating long-term remodeling. Functional analyses revealed substantial changes in metabolic pathways, suggesting microbiota-driven adaptations to energy utilization under high-altitude hypoxic conditions. In summary, acute high-altitude exposure caused dramatic changes in gut microbiota, while prolonged exposure led to structural and functional reshaping. These findings enhance our understanding of how high-altitude environments reshape gut microbiota. IMPORTANCE: This study is the first to investigate the impact of high-altitude exposure on gut microbiota adaptation in a large-scale longitudinal cohort. It seeks to enhance understanding of how high-altitude environments reshape gut microbiota. Acute exposure to high altitude significantly affected both α-diversity and β-diversity of gut microbiota, with acute exposure causing more pronounced changes than prolonged adaptation, indicating temporary disruptions in microbial communities. Notable shifts in microbial abundance were observed, including increased levels of genera linked to hypoxic stress (e.g., Gemmiger, Ruminococcus, and Parabacteroides) and decreased levels of beneficial bacteria (e.g., Faecalibacterium, Roseburia, and Bifidobacterium), suggesting possible adverse health effects. Functional analysis indicated changes in metabolism-related pathways post-exposure, supporting the idea that high-altitude adaptations involve metabolic adjustments for energy management. These findings enhance understanding of high-altitude physiology, illustrating the role of gut microbiota in hypoxic health.

Experiment 1


Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/04

Curator: YokoC

Revision editor(s): YokoC

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
High altitude adaptation High altitude adaptation,high altitude adaptation
Group 0 name Corresponds to the control (unexposed) group for case-control studies
G-II + G-III (Group 2 and 3)
Group 1 name Corresponds to the case (exposed) group for case-control studies
G-I (Group 1 at 800 m)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of healthy adult males at the baseline at 800 m altitude.
Group 0 sample size Number of subjects in the control (unexposed) group
592
Group 1 sample size Number of subjects in the case (exposed) group
406
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/05

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 5C

Description: LEfSe differential analysis comparing the baseline group at 800 m. of altitude vs. acute high-altitude group and prolonged high-altitude group after a 2 week return from 3 months at 4500 m).

Abundance in Group 1: increased abundance in G-I (Group 1 at 800 m)

NCBI Quality ControlLinks
Actinomycetes
Actinomycetota
Alloprevotella
Anaerostipes
Bilophila
Blautia
Butyricicoccus
Collinsella
Coriobacteriaceae
Coriobacteriales
Dorea
Enterobacterales
Enterobacteriaceae
Erysipelotrichaceae
Erysipelotrichales
Erysipelotrichia
Faecalibacterium
Flavonifractor
Fusicatenibacter
Gammaproteobacteria
Pseudomonadota
Clostridium XVIIIClostridium XVIII
Ruminococcus 2Ruminococcus 2
Escherichia/Shigella sp.

Revision editor(s): YokoC

Experiment 2


Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
G-I + G-III (Group and 3)
Group 1 name Corresponds to the case (exposed) group for case-control studies
G-2 (Group 2 acute altitude at 4500 m)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of healthy adult males seven days after ascending to 4,500 m.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 5C

Description: LEfSe differential analysis comparing the acute high-altitude group at 4500 m vs. the baseline group at 800 m. of altitude and prolonged high-altitude group (after a two week return from 3 months at 4500 m).

Abundance in Group 1: increased abundance in G-2 (Group 2 acute altitude at 4500 m)

NCBI Quality ControlLinks
Akkermansia
Alistipes
Barnesiella
Betaproteobacteria
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Burkholderiales
Butyricimonas
Coprococcus
Deltaproteobacteria
Desulfovibrionaceae
Desulfovibrionales
Dialister
Gemmiger
Methanobacteria
Methanobacteriaceae
Methanobacteriales
Methanobacteriota
Methanobrevibacter
Mitsuokella
Odoribacter
Oscillibacter
Parabacteroides
Porphyromonadaceae
Rikenellaceae
Ruminococcus
Sutterellaceae
Verrucomicrobiaceae
Verrucomicrobiales
Verrucomicrobiia
Verrucomicrobiota
Clostridium IVClostridium IV
Archaea

Revision editor(s): YokoC

Experiment 3


Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
G-I + G-II (Group 1 and 2)
Group 1 name Corresponds to the case (exposed) group for case-control studies
G-3 (Group 3 after prolonged altitude at 800 m)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of healthy adult males two weeks post-return to 800 m following 3 months at high altitude
Group 0 sample size Number of subjects in the control (unexposed) group
812
Group 1 sample size Number of subjects in the case (exposed) group
186

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 5C

Description: LEfSe differential analysis comparing the prolonged high-altitude group (after a two week return from 3 months at 4500 m) vs. the baseline group at 800 m. of altitude and acute high-altitude group at 4500 m.

Abundance in Group 1: increased abundance in G-3 (Group 3 after prolonged altitude at 800 m)

NCBI Quality ControlLinks
Butyrivibrio
Fusobacterium
Lachnospiraceae
Lachnospiraceae incertae sedis
Megamonas
Mucispirillum
Roseburia
Clostridium XIVaClostridium XIVa
Clostridium XIVbClostridium XIVb
Bacteria

Revision editor(s): YokoC

Experiment 4


Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
G-I (Group 1 baseline)
Group 1 name Corresponds to the case (exposed) group for case-control studies
G-2 (Group 2 acute altitude exposure at 4500 m)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of healthy adult males seven days after ascending to 4,500 m.
Group 0 sample size Number of subjects in the control (unexposed) group
406
Group 1 sample size Number of subjects in the case (exposed) group
406

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 5A. Within text, Results under "Unique microflora characteristics" section.

Description: Box plots for differential analysis of gut microbiota at the genus level between the acute high-altitude exposure group at 4500 m. vs. the baseline group at 800 m.

Abundance in Group 1: increased abundance in G-2 (Group 2 acute altitude exposure at 4500 m)

NCBI Quality ControlLinks
Alistipes
Gemmiger
Oscillibacter
Parabacteroides
Ruminococcus
Escherichia/Shigella sp.

Revision editor(s): YokoC

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 5A. Within text, Results under "Unique microflora characteristics" section.

Description: Box plots for differential analysis of gut microbiota at the genus level between the acute high-altitude exposure group at 4500 m. vs. the baseline group at 800 m.

Abundance in Group 1: decreased abundance in G-2 (Group 2 acute altitude exposure at 4500 m)

NCBI Quality ControlLinks
Alloprevotella
Faecalibacterium
Megamonas
Roseburia

Revision editor(s): YokoC

Experiment 5


Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
G-3(Group 3 prolonged altitude exposure at 4500 m.)
Group 0 sample size Number of subjects in the control (unexposed) group
186

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 5A, Within text, Results under "Unique microflora characteristics" section.

Description: Box plots for differential analysis of gut microbiota at the genus level between the acute high-altitude exposure group at 4500 m. and the prolonged high-altitude exposure group, two weeks post-return to 800 m following 3 months at high altitude.

Abundance in Group 1: increased abundance in G-2 (Group 2 acute altitude exposure at 4500 m)

NCBI Quality ControlLinks
Alistipes
Gemmiger
Oscillibacter
Parabacteroides
Ruminococcus
Escherichia/Shigella sp.

Revision editor(s): YokoC

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 5A, Within text, Results under "Unique microflora characteristics" section.

Description: Box plots for differential analysis of gut microbiota at the genus level between the acute high-altitude exposure group at 4500 m. and the prolonged high-altitude exposure group, two weeks post-return to 800 m following 3 months at high altitude.

Abundance in Group 1: decreased abundance in G-2 (Group 2 acute altitude exposure at 4500 m)

NCBI Quality ControlLinks
Faecalibacterium
Roseburia
Megamonas
Alloprevotella

Revision editor(s): YokoC

Experiment 6


Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/21

Curator: YokoC

Revision editor(s): YokoC, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Smoking behavior smoking,Smoking behavior,smoking behavior
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Non-Smokers
Group 1 name Corresponds to the case (exposed) group for case-control studies
Smokers
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of healthy adult males who smoke.
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified

Lab analysis

Statistical Analysis

Statistical test
Spearman Correlation


Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 7

Description: Heatmap of a Spearman correlation analysis of genera with lifestyle factors (smoking).

Abundance in Group 1: increased abundance in Smokers

NCBI Quality ControlLinks
Roseburia

Revision editor(s): YokoC

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 7

Description: Heatmap of a Spearman correlation analysis of genera with lifestyle factors (smoking).

Abundance in Group 1: decreased abundance in Smokers

NCBI Quality ControlLinks
Odoribacter
Butyricimonas
Parabacteroides
Alloprevotella
Bilophila
Dialister
Clostridium IVClostridium IV
Oscillibacter

Revision editor(s): YokoC

Experiment 7


Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Alcohol drinking alcohol consumption,Alcohol drinking,alcohol drinking
Group 0 name Corresponds to the control (unexposed) group for case-control studies
No alcohol use
Group 1 name Corresponds to the case (exposed) group for case-control studies
Alcohol use
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of healthy adult males who use alcohol.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 7

Description: Heatmap of a Spearman correlation analysis of genera with lifestyle factors (alcohol use).

Abundance in Group 1: increased abundance in Alcohol use

NCBI Quality ControlLinks
Roseburia

Revision editor(s): YokoC

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 7

Description: Heatmap of a Spearman correlation analysis of genera with lifestyle factors (alcohol use).

Abundance in Group 1: decreased abundance in Alcohol use

NCBI Quality ControlLinks
Bifidobacterium
Butyricicoccus
Dorea
Clostridium XIVaClostridium XIVa

Revision editor(s): YokoC

Experiment 8


Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Age Age,age
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Lower age
Group 1 name Corresponds to the case (exposed) group for case-control studies
Higher age
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of healthy adult males between the ages of 18 - 25.

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 7

Description: Heatmap of a Spearman correlation analysis of genera with lifestyle factors (age).

Abundance in Group 1: increased abundance in Higher age

NCBI Quality ControlLinks
Blautia
Fusicatenibacter
Roseburia

Revision editor(s): YokoC

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 7

Description: Heatmap of a Spearman correlation analysis of genera with lifestyle factors (age).

Abundance in Group 1: decreased abundance in Higher age

NCBI Quality ControlLinks
Methanobrevibacter
Collinsella
Bifidobacterium
Oscillibacter

Revision editor(s): YokoC

Experiment 9


Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Body mass index BMI,Quetelet's Index,Body mass index,body mass index
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Lower BMI (Body Mass Index)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Higher BMI (Body Mass Index)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of healthy adult males with a higher Body Mass Index (BMI).

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 7

Description: Heatmap of a Spearman correlation analysis of genera with lifestyle factors (BMI).

Abundance in Group 1: increased abundance in Higher BMI (Body Mass Index)

NCBI Quality ControlLinks
Collinsella

Revision editor(s): YokoC

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 7

Description: Heatmap of a Spearman correlation analysis of genera with lifestyle factors (BMI).

Abundance in Group 1: decreased abundance in Higher BMI (Body Mass Index)

NCBI Quality ControlLinks
Dialister

Revision editor(s): YokoC

Experiment 10


Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Tea consumption measurement Tea consumption measurement,tea consumption measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Lower tea consumption
Group 1 name Corresponds to the case (exposed) group for case-control studies
Higher tea consumption

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-11

Curated date: 2025/05/22

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 7

Description: Heatmap of a Spearman correlation analysis of genera with lifestyle factors (tea consumption).

Abundance in Group 1: increased abundance in Higher tea consumption

NCBI Quality ControlLinks
Methanobrevibacter

Revision editor(s): YokoC