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Microorganisms of the Human Microbiome in Rosacea


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For a long time microorganisms of the skin microbiome have been suggested as a cause of rosacea. The list includes, bacteria, fungusvirus (including phages), and demodex mites. Further, there are some papers that suggest that the gut microbiome may be involved in rosacea. One article comparing identical twins and the skin microbiome reports "Microbial dysbiosis could be one of the factors associated with the pathogenesis of rosacea as well as its comorbidities." [1] This same study concluded, "Our data demonstrate a significant correlation between facial microbiome and severity of rosacea in genetically matched twins and importantly that overall microbiome composition is largely unchanged." Further the study states, "Specifically, we uncovered a positive and a negative association for Gordonia and Geobacillus with rosacea, respectively. Importantly, this was in the background of a largely unchanged microbiome landscape." Furthermore, the fecal microbiome shows an altered state in rosacea patients. [8]

Research into the human microbiome has enhanced our understanding of the importance of this subject and one paper explains:

"The analysis of 16S ribosomal RNA (rRNA) fragments from the human microbiome is emerging as a novel tool for understanding the pathogenesis of human disease. Metagenomic approaches for investigating microbial genomes are being used to determine the potential roles of the microbiotas of the gut, skin, blood, and other human derivatives in chronic inflammatory diseases." [6]

"However, it is suspected that the community of microorganisms in and on the skin, rather than a single species, plays a more causative role in the disease." [9]

While the vast majority of papers focus on bacteria, there is little if any papers investigating virus, archea, protozoa, or helminths associated in rosacea. There are a significant number of papers focusing on demodex. [13]

A Bias With Bacteria as the Focus of Rosacea Research and the Human Microbiome

The study mentioned previously [1], focuses primarily on bacteria, i.e., Gordonia, Blautia, Chryseobacterium, Wautersiella, Geobacillus and unknown genus (phylum Proteobacteria). Most rosacea research papers have a bias towards bacteria and largely ignore other microorganisms in the microbiome such as virus, archea, fungi, protozoa, helminths, and demodex (the article made a cursory mention of demodex, but little discussion on this subject). The human microbiome has a huge diversity and bacteria is simply only a very small part of it. [2]

Such bias towards bacteria ignoring these other microorganisms with only a token mention of other microbes is found in most articles on rosacea since Western Medicine largely ignores these other microorganisms with very little research, usually only focusing on bacteria. This results with such a paltry knowledge of what might be some significant factors in rosacea other than focusing on bacteria. For example, there are more virus types in the human microbiome than bacteria by a factor of ten times yet very little research is done on virus and rosacea. The bias is that bacteria plays a chief role in rosacea resulting in mostly antibiotic treatments and more recently a little probiotic treatment.

There are examples of clinical papers that have bias toward bacteria and only give token mention of other microbes on skin microbiome. For example, a "study [that] provides a glimpse into the skin microbiota in rosacea and its modulation by systemic antibiotics" clearly shows a bias toward bacteria and ignores any other microbes of the skin microbiota. [5] Another study into the blood microbiota in rosacea patients focused entirely on bacteria ignoring all other microbes in the blood. This bias continues in other papers on the skin microbiome. [6]

Another example is a study comparing the skin microbiota between acne and rosacea which concluded, "Investigating the differences between the skin microbiota in acne and rosacea can provide important clues toward understanding the disease progression in each condition." [7] This study ignores virus, demodex, protozoa, archea and any other microbes except the article totally focuses entirely on bacteria. The focus of most studies on the skin microbiome is usually if not always on bacteria. 

"Therefore, to predict the complete metabolism of any molecule by skin microbiome, a curated database of metabolic enzymes (1,094,153), reactions, and substrates from ∼900 bacterial species from 19 different skin sites were used to develop “SkinBug.” [11] "SkinBug" focuses exclusively on bacteria. 

"Recent research has confirmed the increased presence of bacterial genera like Acidaminococcus and Megasphera in the intestinal microbiome and Rheinheimera and Sphingobium in the blood microbiome of rosacea patients." [12]

A paper published in 2021, Microbiota in Rosacea, mentions bacteria, viruses, fungi, and mites, it ignores archea, protozoa or helminths and totally focuses on bacteria or demodex. [13] The following image is shown in this paper discussing the gut-brain-skin axis. 

microbiotaINrosacea.png [13]

Image courtesy of the American Journal of Clinical Dermatology

Research on Other Microbes Besides Bacteria in Rosacea?

The role of the other microorganisms besides bacteria should warrant more attention but who will pay for such studies? Demodex has been an example of the most researched microorganism other than bacteria studies. [3] This is because there are now treatments for demodectic rosacea so there is motive to fund such studies, usually by pharmaceutical companies that market treatments aimed at eradicating the mites. We are grateful that pharmaceutical companies who treat demodectic rosacea fund studies on demodex and rosacea. However, could there be other microbes that could be investigated besides bacteria and demodex mites?

What about research on the other microbes that are in the human microbiome such as virus or protozoa? What role does archea play in rosacea? Do you want to fund such a study? Could 10K members of the RRDi get together and each donate one dollar to fund such a study? Only with your help could we reach such a goal. Think about it. [4]

image courtesy of the Journal of Clinical Laboratory Analysis

"During normal skin homeostasis, the microbes inhabiting the microenvironment keep a balance; however, a disorder of the microenvironment may occur if factors affecting the growth or survival of microorganism change. In addition, changes in microbiota may be due to individual, environmental, or behavioral factors, such as age, gender, climate, hygiene, antibiotic consumption, humidity, temperature, pH, and lipid composition, which may cause dysbiosis. It is therefore of great importance to examine the correlation between microenvironments and rosacea, which may interact with each other....For the better understanding of the microbiology of rosacea, more studies are needed to help illustrate the mechanism of rosacea and contribute to providing more therapeutic approaches based on the controversial studies and opinions expressed in the literature." [10]

Another study focusing on systemic lupus erythematosus (SLE) patients, 20 controls with rosacea and 20 healthy controls were selected as study subjects shows that the compositions and diversity of skin microbiota in SLE patients are changed and have a distinct structural and functional skin microbiota compared with controls. However, the study only focused on bacteria, ignoring all other skin microbiota. [14]


Microbiome-based therapeutic strategies

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End Notes

[1] Exp Dermatol. Author manuscript; available in PMC 2019 Jul 16.
Published in final edited form as:
Exp Dermatol. 2018 Mar; 27(3): 295–298.
Characterization of the facial microbiome in twins discordant for rosacea
Asifa K. Zaidi,1 Katrina Spaunhurst, Daniel Sprockett, Yolandas Thomason, Margaret W. Mann, Pingfu Fu, Christine Ammons, Meg Gerstenblith, Marie S. Tuttle, and Daniel L. Popkin

The main focus of most clinical papers on the human microbiome focuses on bacteria and ignores other microbiota. A typical example is the following: 

Medicine (Baltimore). 2021 Apr 23; 100(16): e25623.
Differences in microbiota between acute and chronic perianal eczema
Ming Ma, BM, Hongmei Lu, MM, Zuozhen Yang, PhD, Li Chen, MM, Yingru Li, BM, and Xiu Zhang, MMe

[2] Human Microbiome, Brady Barrows

"Parasitic diseases are skin conditions caused by insects, worms, protozoa, or coelenterates that may or may not be parasitic."

An Bras Dermatol. 2020 Jan-Feb; 95(1): 1–14.
Published online 2019 Dec 31. doi: 10.1016/j.abd.2019.12.001
PMCID: PMC7058862 - PMID: 32001061
Update on parasitic dermatoses
Alberto Eduardo Cox Cardoso, Alberto Eduardo Oiticica Cardoso, Carolina Talhari, and Monica Santose

"In this review, we will discuss the relationship between the gut and skin microbiome and various dermatological diseases including acne, psoriasis, rosacea, and atopic dermatitis. In addition, we will discuss the impact of treatment on the microbiome and the role of probiotics."

The Skin and Gut Microbiome and Its Role in Common Dermatologic Conditions.
Microorganisms. 2019 Nov 11;7(11):
Ellis SR, Nguyen M, Vaughn AR, Notay M, Burney WA, Sandhu S, Sivamani RK

[3] Demodectic Rosacea

[4] More thoughts on this subject to think about:
Rosacea Research in Perspective of Funding
Rosacea Research in Perspective of Idiopathic Diseases

[5] J Clin Med. 2020 Jan 09;9(1):
Characterization and Analysis of the Skin Microbiota in Rosacea: Impact of Systemic Antibiotics.
Woo YR, Lee SH, Cho SH, Lee JD, Kim HS

Another study on the skin microbiome states, "The collection of all the microorganisms (bacteria, archaea, fungi, protozoa and viruses) that live in a particular environment or biome, their genomes and the surrounding environmental conditions including microbial metabolites (RNA, proteins, short‐chain fatty acids)," but totally focuses on bacteria with no other mention of 'archea, fungi, protozoa or viruses.' 
Int J Cosmet Sci. 2020 Apr; 42(2): 116–126.
Revealing the secret life of skin ‐ with the microbiome you never walk alone
R. Sfriso, M. Egert, M. Gempeler, R. Voegeli, R. Campiche 

Another paper admits to its bias toward bacteria with statement while acknowledging other microbes: 

"Consortia of microbes are found in many niches of the earth, like on various sites of animals and plants, in soil, in water and in the atmosphere, but also in industrial fermentations and biofilms. In this review, we will focus on the human skin microbiota (mainly on bacteria), their currently known relevance in health and disease, and provide an overview of main sequencing‐based methods and bioinformatic tools to measure them."

J Dermatol. 2020 Oct; 47(10): 1110–1118.
Skin microbiota in health and disease: From sequencing to biology
Thomas H. A. Ederveen, Jos P. H. Smits, Jos Boekhorst, Joost Schalkwijk,  Ellen H. van den Bogaard, Patrick L. J. M. Zeeuwen 

[6] Dermatology 2019;235:255–259 DOI: 10.1159/000496968
Characterization of the Blood Microbiota in Korean Females with Rosacea
Yeojun Yun, Han-Na Kim, Yoosoo Chang, Yunho Lee, Seungho Ryu, Hocheol Shin, Won-Serk Kim, Hyung- Lae Kim, Jae-Hui Nam

Another example of a bias toward bacteria with a token mention of fungus and virus in the skin microbiome dysbiosis: 

Am J Clin Dermatol. 2020; 21(Suppl 1): 18–24.
The Skin Microbiome: A New Actor in Inflammatory Acne
Brigitte Dréno, Marie Ange Dagnelie, Amir Khammari, and Stéphane Corvec 

This paper focuses mainly on bacteria with a mention of demodex: 

Microorganisms. 2020 Nov 08;8(11):
Diversity and Composition of the Skin, Blood and Gut Microbiome in Rosacea-A Systematic Review of the Literature.
Tutka K, Żychowska M, Reich A

[7] Exp Dermatol. 2020 Apr 11;:
Comparison of the skin microbiota in acne and rosacea.
Thompson KG, Rainer BM, Antonescu C, Florea L, Mongodin EF, Kang S, Chien AL

[8] J Formos Med Assoc. 2020 May 20;:
An altered fecal microbial profiling in rosacea patients compared to matched controls.
Chen YJ, Lee WH, Ho HJ, Tseng CH, Wu CY
[see the third post in this thread by scrolling down past this first post]

[9] Br J Dermatol. 2020 Jun 13;:
Bacterial and fungal microbiome characterization in patients with rosacea and healthy controls.

Wang R, Farhat M, Na J, Li R, Wu Y

[10]  Clin Lab Anal. 2020 Sep; 34(9): e23363.
Rosacea is associated with conjoined interactions between physical barrier of the skin and microorganisms: A pilot study
Chao Yuan, Yafeng Ma,  Yinjuan Wang,  Xiuli Wang,  Chunyan Qian,  Didier Hocquet,  Shuli Zheng,  Sophie Mac‐Mary,  and Philippe Humbert  

[11] iScience. 2021 Jan 22; 24(1): 101925.
SkinBug: an artificial intelligence approach to predict human skin microbiome-mediated metabolism of biotics and xenobiotics
Shubham K. Jaiswal, Shitij Manojkumar Agarwal, Parikshit Thodum, and Vineet K. Sharma

[12] Acta Microbiol Immunol Hung. 2021 Jan 29;:
Interactions between immune system and the microbiome of skin, blood and gut in pathogenesis of rosacea.
Joura MI, Brunner A, Nemes-Nikodém É, Sárdy M, Ostorházi E

[13] American Journal of Clinical Dermatology volume 21, pages 25–35 (2020)
Microbiota in Rosacea
Hei Sung Kim 

[14] Systemic lupus erythematosus patients have a distinct structural and functional skin microbiota compared with controls

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Yes I think we have to pay attention to the other skin-microbiome interaction also which tend to play a role in rosacea especially I was thinking of bacteriophage (bacteria+virus) which might play a role in rosacea and very few research is going on this rosacea and the idea of research on this theme would open up a new direction for rosacea. Think out loud.

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Low-temperature electron micrograph of a cluster of E. coli bacteria, magnified 10,000 times. Each individual bacterium is oblong shaped. Image courtesy of Wikimedia Commons.

A recent paper on this subject concluded, "An altered fecal microbial richness and composition were observed in rosacea patients. The distinct microbial composition might be related to sulfur metabolism, cobalamin and carbohydrate transport."

J Formos Med Assoc. 2020 May 20;:
An altered fecal microbial profiling in rosacea patients compared to matched controls.
Chen YJ, Lee WH, Ho HJ, Tseng CH, Wu CY

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"Most of the research performed has focused on bacteria. Bacteria are nonetheless not the only inhabitants of human skin. Additionally, fungi, phages and micro-eukaryotes are present on the skin and most likely play a role in normal skin homeostasis."

Comput Struct Biotechnol J. 2021; 19: 624–631. Published online 2021 Jan 4. doi: 10.1016/j.csbj.2021.01.001
Skin microbiome transplantation and manipulation: Current state of the art
Chris Callewaert, Nastassia Knödlseder, Ante Karoglan, Marc Güell, Bernhard Paetzold

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While the following conclusion is a valid point of this article on the skin microbiome, it totally focuses on bacteria. 

"Further research on the skin microbiome in inflammatory skin diseases is needed, particularly concerning the impact of antibiotics on the microbiome and the beneficial effects of topical probiotics in improving skin health and the individualized treatment of skin diseases."

Features of the Skin Microbiota in Common Inflammatory Skin Diseases

A similar approach focusing again on bacteria states the following: 

"This is a compelling area for future research, and to achieve this objective microbiota research should focus on a much more integrative model that takes into account the target microbiota but also other supposedly unrelated microbiotas."

Human Microbiota Network: Unveiling Potential Crosstalk between the Different Microbiota Ecosystems and Their Role in Health and Disease

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"The skin microbiome includes bacteria, fungi, viruses, micro-eukaryotes (mites), archaea, and phages. They can be found not only on the surface of the epidermis, but also in sweat, sebaceous glands and associated hair follicles. The composition of microbiome differs among different regions affected by numerous factors including age, gender, genetics, immunity, hormonal balance, sleep routine, stress, metabolic factors, hygiene and skin care routine, chemical or ultraviolet radiation exposure, physical activity, climate, environmental pollution and availability of nutrients."

"The studies have shown that probiotics and prebiotics both administered orally or applied topically may have a positive influence on the course of skin diseases. Despite the continuous increase in promising data on the effectiveness of the use of probiotics and prebiotics, further clinical trials are needed to assess the efficacy and long-term safety profile of probiotics and prebiotics in the treatment of patients with dermatological diseases."

Biomedicines. 2021 Oct; 9(10): 1436.
Microbiome Modulation as a Therapeutic Approach in Chronic Skin Diseases
Karina Polak, Antal Jobbágy, Tomasz Muszyński, Kamila Wojciechowska, Aleksandra Frątczak, András Bánvölgyi, Beata Bergler-Czop, and Norbert Kiss

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