Gut Microbiota and Metabolome Changes in Three Pulmonary Hypertension Rat Models

Luo, Lingjie; Yin, Haoyang; Gou, Deming

doi:10.3390/microorganisms11020472

Cited by 6 publications

(4 citation statements)

References 45 publications

(56 reference statements)

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“…While we did not assess whether the protective effect of soluble-fiber in HPH was dependent on SCFA production, in the deoxycortisone acetate-salt mouse model of systemic hypertension, the protective effect of dietary-fiber was phenocopied by treatment with the SCFA acetate, 7 propionate supplementation has been shown to protect against angiotensin II-induced systemic hypertension, 40 and butyrate has been shown to protect against HPH in rats. 41 In addition to the SCFA-promoting effects of the HSFiD, in hypoxic mice we found that the lack of soluble-fiber increased the abundance of Romboutsia , Clostridioides , and Streptococcus— 3 genera that have been shown to be elevated in rodent models of PH, 42 partially overlap with genera that are enriched in PAH and chronic obstructive pulmonary disease patients, 14,43 and are associated with inflammation. These data suggest a detrimental effect of LSFiD.…”

Section: Discussionmentioning

confidence: 74%

High-Soluble-Fiber Diet Attenuates Hypoxia-Induced Vascular Remodeling and the Development of Hypoxic Pulmonary Hypertension

Pakhomov,

Kostyunina,

Macori

et al. 2023

Hypertension

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BACKGROUND: Hypoxic pulmonary hypertension is a difficult disease to manage that is characterized by sustained elevation of pulmonary vascular resistance and pulmonary artery pressure due to vasoconstriction, perivascular inflammation, and vascular remodeling. Consumption of soluble-fiber is associated with lower systemic blood pressure, but little is known about its ability to affect the pulmonary circulation. METHODS: Mice were fed either a low- or high-soluble-fiber diet (0% or 16.9% inulin) and then exposed to hypoxia (FiO 2 , 0.10) for 21 days to induce pulmonary hypertension. The impact of diet on right ventricular systolic pressure and pulmonary vascular resistance was determined in vivo or in ex vivo isolated lungs, respectively, and correlated with alterations in the composition of the gut microbiome, plasma metabolome, pulmonary inflammatory cell phenotype, and lung proteome. RESULTS: High-soluble-fiber diet increased the abundance of short-chain fatty acid-producing bacteria, with parallel increases in plasma propionate levels, and reduced the abundance of disease-related bacterial genera such as Staphylococcus , Clostridioides, and Streptococcus in hypoxic mice with parallel decreases in plasma levels of p-cresol sulfate. High-soluble-fiber diet decreased hypoxia-induced elevations of right ventricular systolic pressure and pulmonary vascular resistance. These changes were associated with reduced proportions of interstitial macrophages, dendritic cells, and nonclassical monocytes. Whole-lung proteomics revealed proteins and molecular pathways that may explain the effect of soluble-fiber supplementation. CONCLUSIONS: This study demonstrates for the first time that a high-soluble-fiber diet attenuates hypoxia-induced pulmonary vascular remodeling and the development of pulmonary hypertension in a mouse model of hypoxic pulmonary hypertension and highlights diet-derived metabolites that may have an immuno-modulatory role in the lung.

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Section: Discussionmentioning

confidence: 74%

High-Soluble-Fiber Diet Attenuates Hypoxia-Induced Vascular Remodeling and the Development of Hypoxic Pulmonary Hypertension

Pakhomov,

Kostyunina,

Macori

et al. 2023

Hypertension

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“…Interestingly, the variability of α-diversity in the HySu rats was similar to the group given MCT. This may indicate similarities of the gut microbiota in PAH type 1 and PAH type 3 [16].…”

Section: Changes In the Gut Microbiota Composition In Pahmentioning

confidence: 88%

Gut–Lung Axis in Focus: Deciphering the Impact of Gut Microbiota on Pulmonary Arterial Hypertension

Suswał,

Tomaszewski,

Romaniuk

et al. 2023

JPM

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Recent advancements in the understanding of pulmonary arterial hypertension (PAH) have highlighted the significant role of the gut microbiota (GM) in its pathogenesis. This comprehensive review delves into the intricate relationship between the GM and PAH, emphasizing the influence of gut microbial composition and the critical metabolites produced. We particularly focus on the dynamic interaction between the gut and lung, examining how microbial dysbiosis contributes to PAH development through inflammation, altered immune responses, and changes in the gut–lung axis. Noteworthy findings include variations in the ratios of key bacterial groups such as Firmicutes and Bacteroidetes in PAH and the pivotal roles of metabolites like trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and serotonin in the disease’s progression. Additionally, the review elucidates potential diagnostic biomarkers and novel therapeutic approaches, including the use of probiotics and fecal microbiota transplantation, which leverage the gut microbiota for managing PAH. This review encapsulates the current state of research in this field, offering insights into the potential of gut microbiota modulation as a promising strategy in PAH diagnosing and treatment.

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“…Compared to healthy controls, MCT‐induced rats exhibited an increased F/B ratio, and several pathogenic species, including Clostridium , Turicibacter , and Mollicutes genera, were predominant [ 116 ]. Actinobacteria, Firmicutes, Proteobacteria abundance increased, and Spirochaetota, Bacteroidetes, unidentified bacteria, and Verrucomicrobi decreased [ 117 , 118 ].…”

Section: Gut Microbiota Profiles Of Phmentioning

confidence: 99%

Promising dawn in the management of pulmonary hypertension: The mystery veil of gut microbiota

Yang,

Zhang,

Wang

et al. 2024

iMeta

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The gut microbiota is a complex community of microorganisms inhabiting the intestinal tract, which plays a vital role in human health. It is intricately involved in the metabolism, and it also affects diverse physiological processes. The gut–lung axis is a bidirectional pathway between the gastrointestinal tract and the lungs. Recent research has shown that the gut microbiome plays a crucial role in immune response regulation in the lungs and the development of lung diseases. In this review, we present the interrelated factors concerning gut microbiota and the associated metabolites in pulmonary hypertension (PH), a lethal disease characterized by elevated pulmonary vascular pressure and resistance. Our research team explored the role of gut‐microbiota‐derived metabolites in cardiovascular diseases and established the correlation between metabolites such as putrescine, succinate, trimethylamine N‐oxide (TMAO), and N, N, N‐trimethyl‐5‐aminovaleric acid with the diseases. Furthermore, we found that specific metabolites, such as TMAO and betaine, have significant clinical value in PH, suggesting their potential as biomarkers in disease management. In detailing the interplay between the gut microbiota, their metabolites, and PH, we underscored the potential therapeutic approaches modulating this microbiota. Ultimately, we endeavor to alleviate the substantial socioeconomic burden associated with this disease. This review presents a unique exploratory analysis of the link between gut microbiota and PH, intending to propel further investigations in the gut–lung axis.

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Gut Microbiota and Metabolome Changes in Three Pulmonary Hypertension Rat Models

Cited by 6 publications

References 45 publications

High-Soluble-Fiber Diet Attenuates Hypoxia-Induced Vascular Remodeling and the Development of Hypoxic Pulmonary Hypertension

High-Soluble-Fiber Diet Attenuates Hypoxia-Induced Vascular Remodeling and the Development of Hypoxic Pulmonary Hypertension

Gut–Lung Axis in Focus: Deciphering the Impact of Gut Microbiota on Pulmonary Arterial Hypertension

Promising dawn in the management of pulmonary hypertension: The mystery veil of gut microbiota

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