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# Editorial: Human microbiota: A key player in the etiology and pathophysiology of cardiovascular and metabolic diseases

Ganesan Velmurugan, Tharmarajan Ramprasath, Gilles Mithieux

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## To cite this version:

Ganesan Velmurugan, Tharmarajan Ramprasath, Gilles Mithieux. Editorial: Human microbiota: A key player in the etiology and pathophysiology of cardiovascular and metabolic diseases. Frontiers in Cardiovascular Medicine, 2022, 9, pp.1081722. 10.3389/fcvm.2022.1081722. inserm-04029902

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OPEN ACCESS

EDITED AND REVIEWED BY
Ichiro Manabe,
Chiba University, Japan

*CORRESPONDENCE
Ganesan Velmurugan
vel@kmchrf.org
Tharmarajan Ramprasath
rtharmarajan@gsu.edu;
rtramprasath@outlook.com
Gilles Mithieux
gilles.mithieux@inserm.fr

SPECIALTY SECTION
This article was submitted to
Cardiovascular Metabolism,
a section of the journal
Frontiers in Cardiovascular Medicine

RECEIVED 27 October 2022

ACCEPTED 14 November 2022

PUBLISHED 05 December 2022

CITATION
Velmurugan G, Ramprasath T and
Mithieux G (2022) Editorial: Human
microbiota: A key player in the etiology
and pathophysiology of cardiovascular
and metabolic diseases.
Front. Cardiovasc. Med. 9:1081722.
doi: 10.3389/fcvm.2022.1081722

COPYRIGHT
© 2022 Velmurugan, Ramprasath and
Mithieux. This is an open-access
article distributed under the terms of
the Creative Commons Attribution
License (CC BY). The use, distribution
or reproduction in other forums is
permitted, provided the original
author(s) and the copyright owner(s)
are credited and that the original
publication in this journal is cited, in
accordance with accepted academic
practice. No use, distribution or
reproduction is permitted which does
not comply with these terms.

# Editorial: Human microbiota: A key player in the etiology and pathophysiology of cardiovascular and metabolic diseases

Ganesan Velmurugan¹*, Tharmarajan Ramprasath²* and
Gilles Mithieux³*

¹Chemomicrobiomics Laboratory, Department of Biochemistry and Microbiology, KMCH Research Foundation, Coimbatore, Tamil Nadu, India, ²Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA, United States, ³Centre National de la Recherche Scientifique (CNRS), Paris, France

KEYWORDS

microbiota, gut bacteria, metabolic diseases, atherosclerosis, cardiovascular disease, human microbiota

Editorial on the Research Topic

Human microbiota: A key player in the etiology and pathophysiology
of cardiovascular and metabolic diseases

The human microbiota is equivalent to the major organs of the adult human body like the brain and liver, in terms of weight (~1.5 kg) and functionality. The gut, oral cavity, skin, and vagina are major residing homes of the human microbiota. The human microbiota comprises bacteria, viruses, archaea, fungi, and protozoans. Recent studies have revealed the presence of functional microbiota in blood, atherosclerotic plaques, adipose tissues, and other organs. Microbiota and their metabolites play a key role in insulin resistance, atherosclerotic plaque formation, inflammation, oxidative stress, and the metabolism of drugs and chemicals (1). Increasing evidence indicates their key role in the etiology and pathophysiology of different cardiovascular diseases and metabolic diseases. This Research Topic aimed to cover the recent findings on the role of gut microbiota during cardiovascular and metabolic diseases.

The metabolic risk factors, including diabetes, hypertension, and hypercholesterolemia in combination with genetics and lifestyle factors contribute to the etiology of cardiovascular diseases. Guo et al. conduct a systematic review of human observational studies interlinking gut microbiota and hypertension. The database search, as per PRISMA guidelines, resulted in 17 studies with 9,085 participants. The
comprehensive analysis of all studies shows gut microbial
dysbiosis with decreased diversity and changes in
microbial metabolites, specifically short-chain fatty acids,
during hypertension.

Yet another major risk factor for cardiovascular diseases is
diabetes, which is characterized by an increase in blood glucose.
To investigate the role of gut microbiota on the regulation of
blood glucose during heart failure, Bao et al. employed a mice
heart failure model by performing thoracic aortic constriction
followed by an antibiotic cocktail treatment to deplete the
microbiota. The microbiota-depleted heart failure mice model
showed decreased glucose intolerance and glucagon levels. The
changes in gut microbial structure were studied by sequencing
and metabolomics. Further, fecal microbiota transplantation
experiments reveal the role of microbiota in mediating blood
glucose metabolism during heart failure in mice models.

Uric acid is an unexplored marker for heart failure and
gut microbiota involves in the metabolism of purines and uric
acids (2). In order to validate the potential of serum uric acid
as a prognostic marker for heart failure with reduced ejection
fraction (HFpEF), Wang et al. investigate the association between
hyperuricemia and heart failure parameters in the participants
of two large prospective cohort studies. The analysis reveals
the association of hyperuricemia with left ventricular ejection
fraction recovery and long-term adverse events of heart failure.

Studies have documented the variation in gut microbiota
between heart failure patients and healthy controls but fewer
studies have attempted to investigate the variation within
patients with cardiovascular disease categorized based on
any clinical parameters. Heart failure with preserved ejection
fraction (HFpEF) is becoming predominant among heart failure
conditions. Hence, Huang et al. conduct a preliminary study
to understand the variation in gut microbiota during HFpEF.
The study includes 30 patients with HFpEF and 30 healthy
individuals and gut microbiota profiling. Although no changes
in alpha diversity were noticed, a significant variation of
microbiota was observed in beta diversity analysis. The authors
discuss the probable role of significantly differentially expressed
bacteria on host inflammation and metabolic factors.

Atherosclerosis is the thickening of the blood vessel that aids different cardiovascular diseases. Aside from the different molecular pathways proposed for the formation of atherosclerotic plaques, recent research also suggests the role of microbial metabolites in this process (3). The blood acts as an arsenal of numerous microbial metabolites that drives cardiac function and pathology (4). Focusing particularly on plaque stability, Shen et al. review its relationship with gut microbiota. A wide range of data on different microbial metabolites such as short-chain fatty acids, trimethylamine-N-oxide, and their molecular pathway leading to thrombus formation are discussed. In addition, the future therapeutic perspectives based on intervention in microbiota are elaborately presented.

Dietary exposure, environment, and host genetics are the key
players in shaping the microbiota of a human (5). The impact
of food constituents on gut microbiota is well-established and
easily modifiable and thereby provides the scope of dietary-
mediated gut microbial restoration as a therapeutic approach.
Yang et al. employed the *in vitro* and mice models to investigate
the impact of Chinese rice wine metabolites on gut microbiota
and subsequent impacts on diabetic cardiomyopathy. The
mice treated with rice wine polyphenols and polypeptides
led to a proliferation of *Akkermansia* and depletion of
*Desulfovibrio* genera. A significant correlation was observed
between the cardiac markers and microbiota profile, indicating
the microbiota-mediated therapeutic impact.

The gut microbiota interacts with numerous host factors and thereby influences host physiology and pathology. Numerous studies have revealed the role of microRNAs (miRNAs), the small, non-coding RNAs of mammalian origin that negatively regulate gene expression at the post-transcriptional stage. During the past decade, several studies have revealed the role of gut microbiota and miRNAs in different cardiovascular diseases (6). Ionescu et al. provide a comprehensive review of the studies related to microbiota and miRNAs and propose the mechanisms for the synergism between gut microbiota and host miRNAs during cardiovascular diseases.

Recent studies explored the presence of microbiota in traditionally considered sterile tissues such as the liver, pancreas, breast tissue, and bone in both healthy and cancer tissues (7). In continuation of this exploration, Shanmuganathan et al. investigate the variation in the microbiota of human intervertebral disc tissue of healthy donors and patients with cardiovascular diseases undergoing surgery. The study reveals the abundance of proteobacteria (particularly the *Pseudomonas* genus) and firmicutes phyla in the degenerated disks. There is a significant loss in microbial diversity with an abundance of pathogenic bacteria in the degenerated disks.

Overall, this Research Topic provides different dimensions
on the role of human microbiota during cardiovascular
and other metabolic diseases. The major drawback in
microbiota and disease studies is the non-exploration
of the chicken and egg hypothesis, i.e., the cause and
effect. At this moment, further studies are needed to
explore the etiology of changes in the microbiota. We
are hopeful that microbiota-based therapeutic approaches
discussed here including fecal microbiota transplantation,
probiotics, and prebiotic intervention with plant-derived
metabolites will evolve into routine clinical practice in the
near future.

Author contributions

All of the contributors contributed to the Editorial process
and approved this Editorial article.
## Acknowledgments

The authors acknowledge Indo-French Center for Advanced Research (CEFIPRA 6303-3) for funding their research.

## Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships

that could be construed as a potential conflict of interest.

## Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

## References

1. Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. *Nat Rev Microbiol.* (2021) 19:55–71. doi: 10.1038/s41579-020-0433-9

2. Wannamethee SG, Papacosta O, Lennon L, Whincup PH. Serum uric acid as a potential marker for heart failure risk in men on antihypertensive treatment: the British Regional Heart Study. *Int J Cardiol.* (2018) 252:157–92. doi: 10.1016/j.ijcard.2017.11.083

3. Asada Y, Yamashita A, Sato Y, Hatakeyama K. Pathophysiology of atherothrombosis: mechanisms of thrombus formation on disrupted atherosclerotic plaques. *Pathol Int.* (2020) 70:309–22. doi: 10.1111/pin. 12921

4. Velmurugan G, Dinakaran V, Rajendhran J, Swaminathan K. Blood microbiota and circulating microbial metabolites in diabetes and cardiovascular

diseases. *Tr Endocrinol Metab.* (2020) 31:835–47. doi: 10.1016/j.tem.2020. 01.013

5. Qin Y, Havulinna AS, Liu Y, Jousilahti P, Ritchie SC, Tokolyi A, et al. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. *Nat Gen.* (2022) 54:134–42. doi: 10.1101/2020.09.12.20193045

6. Li M, Chen W, Wang Y. The roles of the gut microbiota-miRNA interaction in the host pathophysiology. *Mol Med.* (2020) 26:101. doi: 10.1186/s10020-020-00234-7

7. Nejman D, Livyatan I, Fuks G, Gavert N, Zwang Y, Geller LT, et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. *Science.* (2020) 368:6494. doi: 10.1126/science.aay9189