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Über dieses Buch

Recent research in science establishes a direct relation between human gut and skin. Several species of live microbes inhabit the human skin and intestines which far outnumbers the mammalian cells in the human body. Research interest of Nextgen scientists is focused on beneficially harnessing this microbial population to address skin disorders like acne, rosacea, eczema, premature aging, and skin cancer which are established to be a result of skin-microbiome dysbiosis. This volume highlights evidence-based endeavours of the scientific community in this sector. Currently there is no concrete literature which gives a detailed vision on the relationship between gut microbiota and skin related disorders. This volume is an attempt to put together available data in the area and demonstrate usefulness of probiotics as a new therapeutic option for management of these skin diseases which currently show poor prognosis, high cost of treatment and compromised quality of life of the patient.



1. Gut-Skin Axis: Role in Health and Disease

The human microbiome includes microorganisms and their cumulative genetic details that reside in the human body. Skin, the body’s most external organ and exposed to the external environment, is an ecosystem with 1.8 m2 area. It has a varying epidermal thickness, folds, and appendages in different areas including along with varying moisture and temperature level on the skin surface. Microbial colonization on the skin surface starts from the time of birth. The mode of delivery affects the colonization process to a considerable extent. The group of microbes colonizing the skin surface is determined by physical and chemical features of it, which applies to microbes inhabiting the gut and other ecological niches in the body as well. There is several common important characteristics shared commonly by gut and skin, where both are (1) heavily vascularized, (2) richly perfused, (3) densely innervated, (4) integrated to the immune system, (5) highly associated with the endocrine system, (6) extensively colonized with recognizable microbiota, and (7) both helps our body to communicate with its external environment. It has variously been reported that a close and bidirectional association within the gut and skin in maintaining the homeostasis and allostasis of skin and also gastrointestinal (GI) health. Therefore, numerous intestinal pathologies have been linked to skin comorbidities. It has been found that skin is directly impacted by the various circumstances that principally affect the intestine. Similarly, various gastrointestinal disorders could be linked to distinct dermatological entities. In the same context, a growing body of proof proposes an association of intestinal dysbiosis with many regular inflammatory skin pathologies including atopic dermatitis (AD), psoriasis, rosacea, and acne vulgaris. And the realization of this interconnected association between skin and gut has resulted in a new concept of the “Gut-Skin Axis.” An intimate bidirectional engagement between the gut and the skin has been well established by growing research evidence in this domain. Recent reports have indicated that the administration of specific Lactobacilli strains to mice can significantly alter the overall skin phenotype. Despite increasing research efforts in this domain, a systematic investigation of the “Gut-Skin Axis” remains ill explored by both gastroenterology as well as dermatology researchers. And in this context, here we are discussing various aspects of the Gut-Skin Axis and its role in the general well-being of individuals.
Alok Malaviya, K. Vamsi Krishna, Shruti Malviya, T. Nimisha Das

2. Mechanistic Role of Probiotics in Improving Skin Health

Skin is an ecosystem of massive microorganisms, and its dynamic interaction with this flora confers it with barrier characteristics on it. Today’s stressors, such as pollution, dietary choices, and other immunological and hormonal changes, can still tip the scales in favour of disease, including infections. Steroids and/or antibiotics are generally used to treat the latter. However, the cost of therapy, the resulting side effects, and the prevalence of antibiotic resistance necessitate the use of less expensive and natural alternatives. Topical probiotic treatment can help control illness and regulate skin flora, according to clinical and experimental studies. The gut–skin axis, now a well-established fact, suggests that a healthy gut flora is important for a normal and healthy skin condition and that oral probiotic supplementation might help control inflammatory skin disorders like acne. Direct modification of skin flora by topical probiotic treatment, on the other hand, might have far-reaching consequences. They have a variety of functions, including the generation of antimicrobial compounds, the prevention of pathogen adherence, and the activation of the immune system, as well as the ability to colonise the skin surface. This chapter discusses various mechanisms through which probiotics elicit their beneficial effects along with their implications in various skin disorders. Delivery of these beneficial microorganisms to skin is highly challenging. Maintenance of probiotic viability during manufacturing and storage; their retention on skin for sufficiently long periods; and their germination on skin surface after application are the major formulation challenges which need redressal.
Garima Sharma, Garima Khanna, Pratibha Sharma, Parneet Kaur Deol, Indu Pal Kaur

3. Skin Microbiome and Host Immunity: Applications in Regenerative Cosmetics and Transdermal Drug Delivery

Recent advances in our understanding of the function of the skin and its microbiome have shown that there is a strong symbiotic relationship between the microbiota of the skin and its host immune functions. The dysbiosis or imbalance of the microbiome and other factors that have an influence on the surface microbiota can influence keratinocyte regulation and homeostasis as well as the skin barrier function. In this perspective paper, we review the evidence that connects the skin’s microbiome and the barrier function of the epidermis and explore the future potential for applying this unique dialogue in developing innovative cosmetics and transdermal drugs for well-being and beauty. Lay abstract: The microbiome on the skin has a unique dialogue with the host through the host immune system. This dialogue makes the basis of several host immune responses and helps shape the host immunity. In this article, we explore this microbiome and host interaction and see how this can influence our understanding of skin barrier function and future applications toward transdermal delivery of topicals.
Kavita Beri

4. Probiotics and Their Various Forms Supporting Skin Health

There is increasing evidence for a gut-skin axis and a potential influence of the skin microbiota on skin health. With this in mind, there is an opportunity for probiotics, even though they have traditionally been investigated for their intestinal and immune benefits. The skin has an important function as a barrier. Here, oral and topical probiotics, parabiotics, and postbiotics have been observed to have positive benefit, also in supporting the skin against UV-induced damage. The manufacturing of probiotics for skin health, especially for topical applications, may have very specific requirements, different from current oral applications, because the intended use and regulation are different. For the future, the field would benefit from rigorous human intervention studies as are becoming more common in the nutritional field. While currently mainly typical probiotic organisms such as lactobacilli and bifidobacteria are used, it can be foreseen that in the future also organisms representative for the skin microbiota will find application.
Laura Huuskonen, Heli Anglenius, Kirsti Tiihonen, Arthur C. Ouwehand

5. Topical Probiotics: Scope and Challenges

A significant upsurge has been discerned on the utilization of probiotics in the amelioration of skin associated disorders since the commencement of the twenty-first century. An extended therapeutic profile where topical probiotic therapies can be exercised has been discovered, such as inflammation, fungal infections, microbial infection, and treatment of atopic dermatitis. Topical therapy with Lactobacillus, Nitrosomonas, Streptococcus, and Bifidobacterium has shown to ameliorate skin inflammation by prompting decolonization of pathogens that reside on the skin such as Pseudomonas aeruginosa, Escherichia coli, Cutibacterium acnes, Acne vulgaris, etc. However, none of the probiotics have been approved to be labelled as “drugs” by the US Food and Drug Administration. Even though the emerging therapeutic effects of probiotics potentiate a wider therapeutic usage, it still necessitates a thorough assessment for its safety and efficacy profile. A review on the present-day topical probiotic therapy was formulated, and the scope and challenges associated with the therapy are discussed in the chapter.
Aakriti Sethi, Jinyan Tao

6. Status of Using Probiotic Supplementation in Acne

Skin conditions like acne vulgaris have been linked to hormonal imbalance as well as microbiota pertaining to the brain-gut-skin axis. Having acne and distressed skin conditions also have links to cognitive and behavioural indisposition, often due to deficiency of certain nutrients and thereby giving rise to the approaches discussing gut-brain-skin axis. This has been addressed widely by the supplementation of diet with probiotics. This keeps the human skin microbiome in check, thereby eliminating the growth of commensal skin bacteria and maintaining skin microbiome homeostasis. The use of probiotics has proven beneficial in acne conditions facing antibiotic resistance and inhibiting inflammation in severe cases. This has increased the demand for oral probiotics to modulate and treat skin conditions. This section will focus on different approaches in the use of such probiotic supplements for treating acne, various interplaying factors, effects, and advancements.
Aishwarya Hattiholi, Shivani Tendulkar, Suneel Dodamani

7. Probiotic Effects on Skin Health: The Case of Photoprotection as a Model of Gut-Skin Dialog

The skin is the most external organ of our body, and it is constantly exposed to environmental challenges. In this way, ultraviolet radiation (UVr) contained within sunlight is one of the most important insults that our skin deals with. UVr deeply affects skin cells, promoting DNA damage, oxidative stress, and mitochondrial alterations, all of which lead to local inflammation after acute exposures and to skin carcinogenesis after chronic ones. Additionally, UVr can also alter our immune system, suppressing adaptive immune responses.
Probiotic microorganisms are very well known for their capacity to modulate the immune system, mainly at the gastrointestinal tract. However, orally administered probiotics also affect skin immunity. It has been demonstrated that different oral probiotic formulations may impact skin health. Whole microorganisms, as well as isolated molecules, have proven to be effective in skin photoprotection, avoiding detrimental effects of UVr on the skin. Some of these effects have been shown, such as a protection against UV-induced immunosuppression, carcinogenesis, loss of Langerhans cells, and other effects that will be summarized in the present chapter.
The mechanisms responsible for the translocation of the effects from the gut epithelium to the skin and its draining lymph nodes are still poorly understood, but some hypotheses will be set out here, considering the effects of probiotics on the gut-associated lymphoid tissue.
Daniel Gonzalez Maglio, Adrián Friedrich, Eliana Cela, Mariela Paz, Juliana Leoni

8. Relationship Between Probiotics and Gut-Skin Axis in Skin Wound Healing: A Recent Update

There is an intricate relationship between human skin health and gut microenvironment, and both are equally influenced using probiotics. In recent years, there is growing evidence suggesting the role of probiotics in metabolism, immunomodulation, wound healing, and various inflammatory and infectious conditions. Both the skin and gut are morphologically different but share some common physiological features. The gut and skin interact mainly through this microbiota and the metabolites secreted by them that interfere with a cascade of biological pathways regulating metabolism, immunity, inflammation, oxidative stress, and neuroendocrine function. Understanding the mechanism of action by which gut influences skin health (inside-out) is essential to define the cross talk between the two compartments. Probiotics can be exploited as modern therapeutics or as an adjuvant to classical therapies in the management of a variety of human diseases. However, limited data is available on the clinical potential of oral and topical probiotics in the treatment of skin- and gut-associated diseases. Although probiotics are considered safe, a comprehensive investigation is also required to establish the safety measures in immunocompromised persons. The present review highlighted the significance of probiotics in the gut-skin axis with a special reference to gut microbiota, skin homeostasis, and skin wound healing.
Manoj Kumar Tembhre, Mehma Kaur Chawla, Francois Berthiaume, Suneel Kumar

9. Probiotics for Atopic Dermatitis: An Update

Atopic dermatitis (AD) is a chronic, inflammatory disorder associated with dry, scaly, and extremely itchy skin having complex pathophysiology. Mostly, symptomatic treatments are offered to AD that include skin moisturizers, antihistaminic, topical steroids, etc. Although exact pathophysiology of AD is not clear, it was reported that along with genetic factors, epidermis dysfunction, and immune system abnormalities, microbiome in the gut-skin axis also contributes for the progression of AD. The alteration in gut flora results in dysbiosis, an imbalance within natural microbiota which causes many health complications including AD. Probiotics are live microorganisms which support gut microbiota and elicit several health benefits when consumed. However, viability and stability of probiotics are the major concerns for their effective usage. Probiotics are available in various conventional dosage forms like tablet, capsules, sachets, oral liquids, etc. Additionally, they are also incorporated into controlled delivery systems using microencapsulation and lyophilization techniques which not only deliver required amount of probiotic at a targeted site but also significantly improve their sustainability. At present, several clinical trials are ongoing for different strains of probiotics and their relevance to microbiota. In the future, new routes and dosage forms can be explored for effective delivery of probiotics in management of AD.
Pratik Kakade, Sarika Wairkar, Shruti Lohakare, Purav Shah, Vandana Patravale

10. Safety Concerns, Regulatory Guidelines, Current Market Trends, and Future Directions toward the Use of Probiotics in Gut-Brain-Skin Axis

The concept of “gut-brain skin axis” is a newly emerging and important avenue of investigation for researchers to treat emotional state (stress, anxiety) and various skin diseases influenced by alteration in normal intestinal microflora. The role of probiotics and correlation between the gut, emotional state, and skin microflora was explored. Before using probiotics as a drug, the parametric assessment in terms of risk versus benefits must carefully be made. Depending on the intended use of a probiotic (drug vs. dietary supplement or food), regulatory requirements differ. However, the position of the regulatory system for probiotics is quite vague and unclear even within the existing categories in the international market which leads to legal uncertainty and confusion. The current market trend like R&D in innovative product development, product launches, brand mergers, or acquisitions for probiotics related to gut-skin and gut-brain axis is studied. It requires more in-depth research for existing and exploring newer potential probiotic strains for varied applications and provides a future direction for probiotic research for routine healthcare practice. This article focuses on safety assessment parameters of probiotic strain, and specific requirements for manufacturing, labeling, and safe delivery, proposed regulatory guidelines by the FDA (for marketing probiotics in a global context) and FSSAI for manufacturing and selling probiotics in an Indian market, approved list of probiotic cultures and licensing of brands, current market trends, and future directions are mentioned.
Swati Misra, Shailendra Raghuwanshi

11. Probiotics as Edible Vaccines

The expansion in the knowledge and applications of probiotics is on a constant rise over decades. The history of vaccine development, on the other hand, ranges back to the early nineteenth century and has been advancing ever since. Design of probiotic-based vaccine has been a boon and can be an important contributor in the field of immunization. Building up the human immunological tolerance has been the aim in order to achieve a superior level of human longevity. Orally deliverable vaccines have been preferred over the conventional parenteral formulations owing to their high patient compliance and ease of delivery. Bacteria and yeast are among the most prevalent microbiota utilized as probiotics, and owing to their significant immunomodulatory effects, they have garnered attention as promising candidates for developing edible vaccine. A legion of organisms has been regarded as safe for human consumption, thereby encouraging their adoption into probiotic-based vaccine development. A variety of bacteria- and yeast-based edible probiotic vaccines are highlighted in this chapter catering to a plethora of physiological conditions in humans. The chapter is majorly devoted to representation of the most frequently applied strategies involving bacteria and yeast in the conception of oral probiotic vaccines, both preclinically and clinically. Despite the presence of conglomerate vaccine-based strategies, a quest for newer probiotic oral vaccine platforms still persists.
Anjali Pandya, Sreeranjini Pulakkat, Sarika Jadhav, Vandana Patravale
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