Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection

Brown, Julia A.; Sanidad, Katherine Z.; Lucotti, Serena; Lieber, Carolin M.; Cox, Robert; Ananthanarayanan, Aparna; Basu, Srijani; Shan, Mengrou; Amir, Mohammed; Schmidt, Fabian; Weisblum, Yiska; Cioffi, Michèle; Li, Tingting; Rowdo, Florencia Madorsky; Martin, Mitchell T.; Guo, Chun-Jun; Lyssiotis, Costas A.; Layden, Brian T.; Dannenberg, Andrew J.; Bieniasz, Paul D.; Lee, Benhur; Inohara, Naohiro; Matei, Irina; Plemper, Richard K.; Zeng, Melody Y.

doi:10.1080/19490976.2022.2105609

Cited by 30 publications

(28 citation statements)

References 72 publications

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“…Other applications include exploring the thanatomicrobiome, in determining the time elapsed since microbial death [ 56 ]. Further applications include tracking the microbiome before and after exposure to diseases like SARS COV2 [ 57 ], and determining changes in the microibial composition following dietary alterations [ 58 , 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

Supervised Machine Learning Enables Geospatial Microbial Provenance

Bhattacharya

Tierney

Ryon

et al. 2022

Genes

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The recent increase in publicly available metagenomic datasets with geospatial metadata has made it possible to determine location-specific, microbial fingerprints from around the world. Such fingerprints can be useful for comparing microbial niches for environmental research, as well as for applications within forensic science and public health. To determine the regional specificity for environmental metagenomes, we examined 4305 shotgun-sequenced samples from the MetaSUB Consortium dataset—the most extensive public collection of urban microbiomes, spanning 60 different cities, 30 countries, and 6 continents. We were able to identify city-specific microbial fingerprints using supervised machine learning (SML) on the taxonomic classifications, and we also compared the performance of ten SML classifiers. We then further evaluated the five algorithms with the highest accuracy, with the city and continental accuracy ranging from 85–89% to 90–94%, respectively. Thereafter, we used these results to develop Cassandra, a random-forest-based classifier that identifies bioindicator species to aid in fingerprinting and can infer higher-order microbial interactions at each site. We further tested the Cassandra algorithm on the Tara Oceans dataset, the largest collection of marine-based microbial genomes, where it classified the oceanic sample locations with 83% accuracy. These results and code show the utility of SML methods and Cassandra to identify bioindicator species across both oceanic and urban environments, which can help guide ongoing efforts in biotracing, environmental monitoring, and microbial forensics (MF).

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Section: Discussionmentioning

confidence: 99%

Supervised Machine Learning Enables Geospatial Microbial Provenance

Bhattacharya

Tierney

Ryon

et al. 2022

Genes

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“…Furthermore, SCFAs boost adaptive immunity through GPCR (GPR41 and GPR43) signaling. Together, these results have shown unexpected roles for SCFAs in preventing hypercoagulation and viral entry while enhancing adaptive antiviral immunity …”

Section: Role Of Scfas In Sars-cov-2 Therapeuticsmentioning

confidence: 94%

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis─A Potential Therapeutic Intervention to Improve Lung Health

Verma,

Bhagchandani,

Rai

et al. 2024

ACS Omega

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The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut−lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut−lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.

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“…From these analyses, it is anticipated that altered microbiomes may affect the outcome of acute COVID infection and may be involved in long-COVID sequelae. More recently, one group demonstrated that treatments with a high-fiber diet containing pectin and/or with mix of SCFAs in the drinking water were both able to reduce the levels of SARS-COV-2 entry receptor angiotensin-converting enzyme 2 (ACE2) and, therefore, to reduce viral burdens in intranasal infection model using mice and hamsters ( 139 ). According to this study, treatments also increased immune adaptive responses via activation of FFAR2 and FFAR3 (but only in males), and reduced coagulation and platelet turnover by regulating the Sh2b3-Mpl axis ( 139 ).…”

Section: Effects Of Butyrate In Distinct Respiratory Diseasementioning

confidence: 99%

“…More recently, one group demonstrated that treatments with a high-fiber diet containing pectin and/or with mix of SCFAs in the drinking water were both able to reduce the levels of SARS-COV-2 entry receptor angiotensin-converting enzyme 2 (ACE2) and, therefore, to reduce viral burdens in intranasal infection model using mice and hamsters ( 139 ). According to this study, treatments also increased immune adaptive responses via activation of FFAR2 and FFAR3 (but only in males), and reduced coagulation and platelet turnover by regulating the Sh2b3-Mpl axis ( 139 ). In this context, in depth analyses of metabolites including SCFAs may emerge a potential new therapeutic in the current and future pandemic.…”

Section: Effects Of Butyrate In Distinct Respiratory Diseasementioning

confidence: 99%

Butyrate: Connecting the gut-lung axis to the management of pulmonary disorders

Corrêa

Castro

Moser³

et al. 2022

Front. Nutr.

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Short-chain fatty acids (SCFAs) are metabolites released by bacterial components of the microbiota. These molecules have a wide range of effects in the microbiota itself, but also in host cells in which they are known for contributing to the regulation of cell metabolism, barrier function, and immunological responses. Recent studies indicate that these molecules are important players in the gut-lung axis and highlight the possibility of using strategies that alter their intestinal production to prevent or treat distinct lung inflammatory diseases. Here, we review the effects of the SCFA butyrate and its derivatives in vitro and in vivo on murine models of respiratory disorders, besides discussing the potential therapeutic use of butyrate and the other SCFAs in lung diseases.

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Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection

Cited by 30 publications

References 72 publications

Supervised Machine Learning Enables Geospatial Microbial Provenance

Supervised Machine Learning Enables Geospatial Microbial Provenance

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis─A Potential Therapeutic Intervention to Improve Lung Health

Butyrate: Connecting the gut-lung axis to the management of pulmonary disorders

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