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Abstract Deeply rooted in its developmental philosophy of gross national happiness (GNH), Bhutan's healthcare system strives towards achieving a shared goal of universal health coverage (UHC). Despite being primarily financed by the government, the health system faces a plethora of challenges. To overcome these hurdles and achieve UHC goals, expanding the fiscal space for health and improving operational efficiency are crucial. This article aims to address Bhutan's evolving healthcare landscape and advance the achievement of UHC through two policy options. The first policy option focuses on the dual objective of improving health outcomes and promoting financial sustainability by leveraging health taxes, whereas the second option emphasizes reinforcing a systematic health technology assessment (HTA) in the Bhutanese health system. First, drawing lessons from global experiences, the policy brief recommends leveraging health taxes to reduce societal and healthcare costs and enhance financial sustainability in the health sector. Considering Bhutan's high prevalence of tobacco and alcohol consumption, and taking opportunity from the ongoing Goods and Services Tax (GST) reform, continued advocacy on health taxes is essential, and soft earmarking the health taxes may be considered to finance a broader array of public health programmes, particularly focusing on the promotion of healthy lifestyle, health screening and outreach public health activities. Second, the integration of HTA into policymaking and decision‐making processes is essential for effective resource allocation in UHC. Nurturing and strengthening the existing HTA governance structure under the Ministry of Health (MoH) and establishing a dedicated multidisciplinary HTA Committee will ensure informed decision‐making and resource optimization. HTA evidence should inform the revision of health service standards, clinical guidelines development, procurement decisions and healthcare priorities. These policy options can assist the country in improving financial sustainability, enhancing effective resource allocation and utilization and improving healthcare delivery, aligning with its vision of GNH and ultimately accelerating progress towards achieving UHC.

Within the fields of forensic anthropology and forensic medicine in general, the ability to provide accurate estimates of time since death that minimize error, maximize precision, and consider a multitude of variables is a critical component of all forensic and medicolegal investigations that focus on the identification of human remains and the circumstances surrounding death. In comparison with many forensic cases where date of death is typically unknown, we begin with a known postmortem interval and progressively assess, through external testing measures (temperature, skin elasticity and skin color changes) followed by photography and videography, decompositional changes over time. This work seeks to provide well-described cases with documented biological parameters to propose hypotheses for future research. Field team members observe and record any decompositional changes associated with the states of algor, rigor, and livor mortis, as well as progressive changes in skin color and tissue integrity in an environment where variability in climate and ecological factors may vary from case to case. The two cases were followed for 31 (postmortem interval [PMI] 38) and 19 (PMI 27) days in humid subtropical and tropical monsoon Köppen-Geiger classified climatic zones, respectively, where delayed decompositional and putrefactive changes observed are at odds with the anticipated rate and expected suite of biological changes occurring within an indoor permeable setting following clinical death. Within this taphonomic context, we also address the value of describing and documenting postmortem intervals in a closed subpopulation from which some individuals are recognized for exhibiting attenuated decompositional changes. This study emphasizes the importance of addressing understudied and underrepresented regions, climates, and cultural contexts for furthering research into the factors that may contribute to the understanding of the early stages of the PMI period and improve the precision of PMI estimates more broadly.

Introduction: Influenza (Flu) causes considerable morbidity and mortality globally, and in Bhutan, Flu viruses are a leading cause of acute respiratory infection and cause outbreaks during Flu seasons. In this study, we aim to analyze the epidemiology and the genetic characterization of Flu viruses circulated in Bhutan in 2022., Method: Respiratory specimens were collected from patients who meet the case definition for influenza-like illness (ILI) and severe acute respiratory infection (SARI) from sentinel sites. Specimens were tested for Flu and SARS-CoV-2 viruses by RT-PCR using the Multiplex Assay. Selected positive specimens were utilized for Flu viral genome sequencing by next-generation sequencing. Descriptive analysis was performed on patient demographics to see the proportion of Flu-associated ILI and SARI. All data were analyzed using Epi Info7 and QGIS 3.16 software., Result: A weekly average of 16.2 ILI cases per 1000 outpatient visits and 18 SARI cases per 1000 admitted cases were reported in 2022. The median age among ILI was 12 years (IQR: 5-28) and SARI was 6.2 (IQR: 2.5-15) years. Flu A(H3N2) (70.2%) subtype was the most predominant circulating strain. Flu A(H1N1)pdm09 and Flu B viruses belonged to subclades that were mismatched to the vaccine strains recommended for the 2021-2022 season but matched the vaccine strain for the 2022-2023 season with vaccine efficacy 85.14% and 88.07% respectively. Flu A(H3N2) virus belonged to two subclades which differed from the vaccine strains recommended in both the 2021-2022 and 2022-2023 seasons with vaccine efficacy 68.28%., Conclusion: Flu virus positivity rates were substantially elevated during the Flu season in 2022 compared to 2021. Flu A(H3N2) subtype was the most predominant circulating strain in the country and globally. Genetic characterization of the Flu viruses in Bhutan showed a close relatedness of high vaccine efficacy with the vaccine strain that WHO recommended for the 2022-23 season., Competing Interests: Authors have declared that no competing interest exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Global warming is exhibiting a seasonal trend, while different seasons have different warming variations. However, the impact of seasonal warming on plants remains unclear. This study employed Open Top Chambers (OTCs) to simulate future seasonal warming scenarios in alpine meadow. The study examined plant community dynamics following long-term seasonal warming. The transcriptional and physiological responses of two dominant species (Kobresia pygmaea and Stipa purpurea) were examined. Results suggest that seasonal warming effects are correlated with both the duration of warming and the season which warming occurs. A long annual warming duration, especially growing season warming, made plants confront various stresses. K. pygmaea adopted a stress-avoidance strategy, showing a negative response, and leading to population decline or disappearance. This kind of dieback had also been observed in other Cyperaceae species. Meanwhile, due to positive responses, S. purpurea adopted a stress-tolerance strategy and overcame the impact of warming, partially gained the dominance over Cyperaceae species. Overall vegetation coverage and plant community diversity decreased over the years. These results reveal the impact of seasonal warming to plants, explaining the reasons for changes in plant communities under seasonal warming and providing new insights for future plant conservation under seasonal warming., (© 2024 John Wiley & Sons Ltd.)

This article delves into Bhutan's adept execution of a nationwide cancer screening initiative within the Health Flagship Programme, concentrating on gastric, cervical, and breast cancers. Despite challenges like the COVID-19 pandemic, infrastructure constraints, logistical complexities, health human resource shortages, and data management issues, the programme succeeded. The procurement and logistics management ensured the timely provision of essential medical equipment and test kits. Robust political commitment, a comprehensive advocacy programme, and community engagement were pivotal for the programme's success. Impressive screening coverage for all three cancers showcased the transformative impact on cancer care, integrating technology and fostering community involvement. Recommendations highlight the need for strengthened integration, strategic approaches, and ongoing evaluation, positioning Bhutan's programme as a potential model for nations facing similar health challenges., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Climate change is one of the biggest challenges facing the world today threatening societies and the future of the planet. The impacts of climate change are more severe in poor and marginalised populations like Indigenous communities where people rely heavily on their Indigenous Knowledge (IK) to adapt to the changing environment. Climate change adaptation and resilience are critical for the survival of Indigenous communities under the threat of climate change. This systematic literature review seeks to understand how IK contributes to climate change adaptation and resilience. A total of 71 papers from Scopus were analysed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. It investigated three research questions: (i) How is IK understood in climate change studies? (ii) What kind of IK is used to address climate change and enhance adaptation and resilience? and finally, (iii) What could be done to maximise the use of IK towards enhancing climate adaptation and resilience? The study found that Indigenous people use IK to predict extreme climatic conditions, prepare for it, and live through it making use of Indigenous adaptation strategies in multiple manifestations. The solutions to maximise the benefits of IK promote two dominant themes requiring more research on IK and climate change with diverse focus areas and the need to bridge it with scientific knowledge. This review provides a starting point for such research that will draw upon IK to enhance climate adaptation and resilience towards meaningful sustainable development., (© 2024. The Author(s).)

N meningiditis remains an important cause of central nervous system infection. A high index of suspicion is required especially in infants. While empirical antibiotics may be initiated, diagnostic measures must be adopted for guided therapy. Notification of such cases contributes to surveillance data and deciding on providing vaccines to the population., Competing Interests: The authors have no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Introduction: Postoperative nausea and vomiting (PONV) are common distressing symptoms experienced after laparoscopic cholecystectomy. We report the rate, and the factors associated with postoperative nausea and vomiting, the patterns of prophylactic antiemetic prescription, and the anesthetic techniques used among patients who underwent laparoscopic cholecystectomy at the Jigme Dorji Wangchuck (JDW) National Referral Hospital, Bhutan., Methods: A cross-sectional study was conducted at the JDW National Referral Hospital, from January to December 2018. All the patients who underwent laparoscopic cholecystectomy under general anesthesia were included in the study. The demographic variables, premedication, induction agents, muscle relaxants, inhalational agents for maintenance, opioid and adjuvant analgesics, the reversal agents used, and the occurrence of PONV within 24 h were recorded. Data were analyzed using SPSS (version 23). Continuous variables were compared using a t-test or Mann-Whitney test, categorical variables were tested using chi-square or Fisher's exact tests. Binary logistic regression analysis was performed to determine the factors associated with postoperative nausea and vomiting., Results: 190 patients underwent laparoscopic cholecystectomy under general anesthesia. The rate of PONV after laparoscopic cholecystectomy was 31.1% (59/190). Over half (53.7%, 102/190) of the study population were within 21-40 years of age, over 80% (157/190) were female, and 2/3rd were overweight and obese. The most frequently used premedication was ranitidine (39%, 34/87) and metoclopramide (31%, 27/87). More than half (57.4%, 109/190) of the patients received morphine as an opioid analgesic before induction. Sodium thiopentone was a commonly used induction agent (65.8%, 125/190). Succinylcholine and atracurium were mostly preferred muscle relaxants. Isoflurane and air were the most used inhalational anesthetic agents for the maintenance of anesthesia. Ondansetron was the most preferred anti-emetics during the intraoperative period. Previous history of motion sickness (OR 5.8, 95%CI 2.9-11.2, p < 0.001), and use of sodium thiopental (OR 4.1, 95%CI 1.9-9.1, p < 0.001) were independent risk factors for PONV. The use of antiemetics (OR 0.1, 95%CI 0.0-0.4, p = 0.002), propofol (OR 0.2, 95%CI 0.1-0.5, p < 0.001), adjuvant analgesic paracetamol (OR 0.4, 95%CI 0.2-0.8, p = 0.026), and adequate hydration with IV fluids (OR 0.9, 95%CI 0.9-1.0, p = 0.042) were preventive factors for PONV., Conclusion: The rate of PONV after laparoscopic cholecystectomy was high. History of motion sickness and use of sodium thiopental for induction were independent risk factors of PONV. The use of multimodal prophylactic antiemetics was robust and superior to monotherapy in preventing PONV. This finding re-emphasizes the need for risk stratification and appropriate use of antiemetics and anesthetic agents to prevent PONV., (© 2024. The Author(s).)

Aflatoxins are mycotoxins that contaminate staple foods globally and pose a significant health risk. To the best of our knowledge, information on the occurrence of aflatoxins in Bhutanese diets is scarce. This study aimed to estimate the aflatoxin levels in selected foodstuffs in Bhutan and determine the health risk associated with aflatoxin exposure. Ten different types of food commodities were randomly collected from farmers' markets, shelves of supermarkets, and wholesale and retail shops from 20 districts of the country. The samples were subjected to analysis by an enzyme-linked immunosorbent assay for both total aflatoxins (B 1 , B 2 , G 1 and G 2) and aflatoxin B 1 . Among the 315 samples included, 48.81% and 79.35% were positive for total aflatoxins and aflatoxin B 1 , respectively. The overall mean total aflatoxin concentration was 11.49 ± 12.83 µg/kg, and that for B 1 was 17.62 ± 23.99 µg/kg. The most prevalent food commodity with the highest aflatoxin contamination was chili products. In addition, the estimated daily intake and margin of exposure to aflatoxin B 1 via the consumption of chili products ranged from 0.98 to 5.34 ng kg -1 bw day -1 and from 74.90 to 408.10, indicating a risk for public health. The liver cancer risk was estimated to be 0.01 and 0.007 cancers per year per 100,000 population resulting from the consumption of chili products. The present findings revealed the presence of total aflatoxins and aflatoxin B 1 in the selected samples. The margin of exposure values was exorbitant, demanding a stringent public health measure. Notably, these results suggest the need for routine monitoring of aflatoxin contamination in the region and stress rigorous safety management strategies to reduce exposure., (© 2024. The Author(s).)

Key Clinical Message: Rheumatic heart disease is a preventable disease. Patients may not present with a typical history of sore throat and polyarthritis but may present with Sydenham's chorea. We should not rely completely on clinical findings to rule out carditis. Echocardiography should be done to rule out subclinical carditis., Abstract: Sydenham's chorea is a major manifestation of rheumatic fever. It occurs primarily in children and is seen rarely after the age of 20 years. We describe a 16-year-old girl who presented with purposeless involuntary movements of her upper and lower limbs. Laboratory blood reports showed raised erythrocyte sedimentation rate and anti-streptolysin O. 2D Doppler Echocardiography confirmed subclinical carditis, thickened mitral and aortic valve with mild mitral regurgitation. She was managed as Acute Rheumatic Fever with oral Phenoxymethyl penicillin and Carbamazepine. At the latest follow-up interviewing the caregiver, the patient had no sequelae. Early diagnosis is key to preventing late consequences of acute rheumatic fever and rheumatic heart disease. Sydenham's chorea is a rare presentation of acute rheumatic fever. The absence of clinical carditis does not rule out carditis., Competing Interests: There is no any conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Extended growing season lengths under climatic warming suggest increased time for plant growth. However, research has focused on climatic impacts to the timing or duration of distinct phenological events. Comparatively little is known about impacts to the relative time allocation to distinct phenological events, for example, the proportion of time dedicated to leaf growth versus senescence. We use multiple satellite and ground-based observations to show that, despite recent climate change during 2001 to 2020, the ratio of time allocated to vegetation green-up over senescence has remained stable [1.27 (± 0.92)] across more than 83% of northern ecosystems. This stability is independent of changes in growing season lengths and is caused by widespread positive relationships among vegetation phenological events; longer vegetation green-up results in longer vegetation senescence. These empirical observations were also partly reproduced by 13 dynamic global vegetation models. Our work demonstrates an intrinsic biotic control to vegetation phenology that could explain the timing of vegetation senescence under climate change.

The term 'druggability' describes the molecular properties of drugs or targets in pharmacological interventions and is commonly used in work involving drug development for clinical applications. There are no current analogues for this notion that quantify the drug-target interaction with respect to a given target variant's sensitivity across a breadth of drugs in a panel, or a given drug's range of effectiveness across alleles of a target protein. Using data from low-dimensional empirical fitness landscapes composed of 16 β-lactamase alleles and 7 β-lactam drugs, we introduce two metrics that capture (i) the average susceptibility of an allelic variant of a drug target to any available drug in a given panel (' variant vulnerability' ), and (ii) the average applicability of a drug (or mixture) across allelic variants of a drug target (' drug applicability '). Finally, we (iii) disentangle the quality and magnitude of interactions between loci in the drug target and the seven drug environments in terms of their mutation by mutation by environment (G x G x E) interactions, offering mechanistic insight into the variant variability and drug applicability metrics. Summarizing, we propose that our framework can be applied to other datasets and pathogen-drug systems to understand which pathogen variants in a clinical setting are the most concerning (low variant vulnerability), and which drugs in a panel are most likely to be effective in an infection defined by standing genetic variation in the pathogen drug target (high drug applicability)., Competing Interests: RG, TD, RH, MS No competing interests declared, CO Reviewing editor, eLife, (© 2023, Guerrero et al.)

Bovine tuberculosis (bTB) is a chronic zoonotic disease affecting cattle of all age groups including wild animals. It poses a significant threat to public health and high economic losses to dairy farmers. While the disease has been eradicated from most of the developed countries through extensive surveillance, testing and culling strategy, it is endemic in Africa, Asia, and the Middle East countries. Currently, there is limited research regarding the prevalence of bTB in cattle in Bhutan. This study aimed to determine the seroprevalence of bTB in cattle in six districts of eastern Bhutan. A two-stage probability proportional to size (PPS) sampling strategy was used to determine the number of animals from which serum samples needed to be collected in each district and sub-district. All farms and cattle for sampling were randomly selected from the data in the annual livestock census of 2020. The samples were tested using bTB ELISA test kit. The seroprevalence and their 95% confidence intervals were calculated. Logistic regression models were constructed to assess the influence of various individual animal and environmental risk factors (breed, age, sex, source of animal, body condition scores of animals, respiratory system status) associated with sero-positivity in animals. The study revealed an apparent seroprevalence of 2.57% (25/971 cattle; 95% CI:1.58-3.57), with an estimated true seroprevalence of 0.91% (95% CI: 0.0-2.81). However, none of the variables were found to be significantly associated with bTB seroprevalence in cattle. We recommend, further sampling and employment of confirmatory testing to fully ascertain the extent of bTB in the cattle herds in eastern Bhutan for prevention and control., Competing Interests: ‘The authors have declared that no competing interests exist., (Copyright: © 2024 Wangmo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

On 31 December 2019, the Municipal Health Commission of Wuhan, China, reported a cluster of atypical pneumonia cases. On 5 January 2020, the WHO publicly released a Disease Outbreak News (DON) report, providing information about the pneumonia cases, implemented response interventions, and WHO's risk assessment and advice on public health and social measures. Following 9 additional DON reports and 209 daily situation reports, on 17 August 2020, WHO published the first edition of the COVID-19 Weekly Epidemiological Update (WEU). On 1 September 2023, the 158th edition of the WEU was published on WHO's website, marking its final issue. Since then, the WEU has been replaced by comprehensive global epidemiological updates on COVID-19 released every 4 weeks. During the span of its publication, the webpage that hosts the WEU and the COVID-19 Operational Updates was accessed annually over 1.4 million times on average, with visits originating from more than 100 countries. This article provides an in-depth analysis of the WEU process, from data collection to publication, focusing on the scope, technical details, main features, underlying methods, impact and limitations. We also discuss WHO's experience in disseminating epidemiological information on the COVID-19 pandemic at the global level and provide recommendations for enhancing collaboration and information sharing to support future health emergency responses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Leishmaniases are a group of diseases under the category of neglected tropical diseases targeted for global elimination. However, they continue to pose major clinical and public health problems, especially among those living in poor socioeconomic conditions. Here, we summarize leishmaniasis elimination efforts in Bhutan. Between 1994 and 2022, Bhutan recorded 54 cases of leishmaniasis across 14 of its 20 districts. There are seven species of Phlebotomus and three species of Sergentomyia sand flies documented in the country. At a subnational level, all endemic districts recorded a visceral leishmaniasis annual incidence <1 per 10,000 population, meeting the regional elimination targets. Serological testing with ELISA and molecular testing with polymerase chain reaction were established at the Royal Center for Disease Control in 2022. A leishmaniasis prevention and management guideline was adopted in 2023 to aid clinicians in diagnosis and management. Active and passive case surveillance was integrated with the national infectious disease early warning and response system. Risk-based entomological surveillance and control have also been prioritized. Climate change may play a major role in rendering districts in the temperate zone favorable for vector proliferation. The country's medical university introduced a diploma course in medical entomology in 2023 to augment the human resources needed for vector surveillance efforts. However, leishmaniasis elimination lacks dedicated programmatic management amid competing priorities for resources against other infectious diseases. Leishmaniasis elimination requires a targeted and programmatic approach in Bhutan, including cross-border collaborative efforts with neighboring Indian states. Bhutan remains highly committed to achieving leishmaniasis elimination targets.

Screening of cancers is an important intervention in reducing the incidence and mortality related to cancers. Bhutan is one small country that is witnessing an increasing incidence and mortality related to cancers. The government implemented a time-bound population-level screening for gastric, cervical and breast cancers from 2020 to 2023 with an overall coverage of 91.2% of the eligible population. Among 370,225 individuals screened for H pylori , 32.4% tested positive; among 53,182 who underwent upper gastrointestinal endoscopy and biopsy, 255 (0.07%) had gastric cancer. Among 10,749 tested for HPV DNA, 9.3% were positive; among 9887 evaluated with colposcopy and biopsy, 154 (0.13%) had cervical cancer. For breast cancer screening, 72,283 underwent clinical breast examination, 845 mammography and cancer was detected in 73 (0.10%) individuals. In this article, we review how Bhutan implemented a population-level cancer screening programme with on boarding of multiple stakeholders and the participation of people across all districts., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

WHO works, on a daily basis, with countries globally to detect, prepare for and respond to acute public health events. A vital component of a health response is the dissemination of accurate, reliable and authoritative information. The Disease Outbreak News (DON) reports are a key mechanism through which WHO communicates on acute public health events to the public. The decision to produce a DON report is taken on a case-by-case basis after evaluating key criteria, and the subsequent process of producing a DON report is highly standardised to ensure the robustness of information. DON reports have been published since 1996, and up to 2022 over 3000 reports have been published. Between 2018 and 2022, the most frequently published DON reports relate to Ebola virus disease, Middle East respiratory syndrome, yellow fever, polio and cholera. The DON web page is highly visited with a readership of over 2.6 million visits per year, on average. The DON report structure has evolved over time, from a single paragraph in 1996 to a detailed report with seven sections currently. WHO regularly reviews the DON report process and structure for improvements. In the last 25 years, DON reports have played a unique role in rapidly disseminating information on acute public health events to health actors and the public globally. They have become a key information source for the global public health response to the benefit of individuals and communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Whole genome sequencing (WGS) can identify clusters, transmission patterns, and drug resistance mutations. This is important in low-burden settings such as Australia, as it can assist in efficient contact tracing and surveillance., Methods: We conducted a retrospective cohort study using WGS from 155 genomically defined drug-resistant Mycobacterium tuberculosis (DR-TB) isolates collected between 2018-2021 in Victoria, Australia. Bioinformatic analysis was performed to identify resistance-conferring mutations, lineages, clusters and understand how local sequences compared with international context., Results: Of the 155 sequences, 42% were identified as lineage 2 and 35% as lineage 1; 65.8% (102/155) were isoniazid mono-resistant, 8.4% were multi-drug resistant TB and 5.8% were pre-extensively drug-resistant / extensively drug-resistant TB. The most common mutations were observed in katG and fabG1 genes, especially at Ser315Thr and fabG1 -15 C>T for first-line drugs. Ser450Leu was the most frequent mutation in rpoB gene. Phylogenetic analysis confirmed that Victorian DR-TB were associated with importation events. There was little evidence of local transmission with only five isolate pairs., Conclusion: Isoniazid-resistant TB is the commonest DR-TB in Victoria, and the mutation profile is similar to global circulating DR-TB. Most cases are diagnosed among migrants with limited transmission. This study highlights the value of WGS in identification of clusters and resistance-conferring mutations. This information is crucial in supporting disease mitigation and treatment strategies., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The extreme environmental conditions of a plateau seriously threaten human health. The relationship between gut microbiota and human health at high altitudes has been extensively investigated. However, no universal gut microbiota biomarkers have been identified in the plateau population, limiting research into gut microbiota and high-altitude adaptation. 668 16s rRNA samples were analyzed using meta-analysis to reduce batch effects and uncover microbiota biomarkers in the plateau population. Furthermore, the robustness of these biomarkers was validated. Mendelian randomization (MR) results indicated that Tibetan gut microbiota may mediate a reduced erythropoietic response. Functional analysis and qPCR revealed that butyrate may be a functional metabolite in high-altitude adaptation. A high-altitude rat model showed that butyrate reduced intestinal damage caused by high altitudes. According to cell experiments, butyrate may downregulate hypoxia-inducible factor-1α (HIF-1α) expression and blunt cellular responses to hypoxic stress. Our research found universally applicable biomarkers and investigated their potential roles in promoting human health at high altitudes.