Prebiotics from Marine Macroalgae for Human and Animal Health Applications

The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the growth and/or activity of beneficial gut microbiota which, in turn, confer health benefits on the host. This review will introduce the concept and potential applications of prebiotics, followed by an outline of the chemistry of seaweed polysaccharides. Their potential for use as prebiotics for both humans and animals will be highlighted by reviewing data from both in vitro and in vivo studies conducted to date.     

On the Health Benefits vs. Risks of Seaweeds and Their Constituents: The Curious Case of the Polymer Paradigm

To exploit the nutraceutical and biomedical potential of selected seaweed-derived polymers in an economically viable way, it is necessary to analyze and understand their quality and yield fluctuations throughout the seasons. In this study, the seasonal polysaccharide yield and respective quality were evaluated in three selected seaweeds, namely the agarophyte Gracilaria gracilis, the carrageenophyte Calliblepharis jubata (both red seaweeds) and the alginophyte Sargassum muticum (brown seaweed). It was found that the agar synthesis of G. gracilis did not significantly differ with the seasons (27.04% seaweed dry weight (DW)). In contrast, the carrageenan content in C. jubata varied seasonally, being synthesized in higher concentrations during the summer (18.73% DW). Meanwhile, the alginate synthesis of S. muticum exhibited a higher concentration (36.88% DW) during the winter. Therefore, there is a need to assess the threshold at which seaweed-derived polymers may have positive effects or negative impacts on human nutrition. Furthermore, this study highlights the three polymers, along with their known thresholds, at which they can have positive and/or negative health impacts. Such knowledge is key to recognizing the paradigm governing their successful deployment and related beneficial applications in humans.     

Anti-Photoaging and Potential Skin Health Benefits of Seaweeds

The skin health benefits of seaweeds have been known since time immemorial. They are known as potential renewable sources of bioactive metabolites that have unique structural and functional features compared to their terrestrial counterparts. In addition, to the consciousness of green, eco-friendly, and natural skincare and cosmetics products, their extracts and bioactive compounds such as fucoidan, laminarin, carrageenan, fucoxanthin, and mycosporine like amino acids (MAAs) have proven useful in the skincare and cosmetic industries. These bioactive compounds have shown potential anti-photoaging properties. Furthermore, some of these bioactive compounds have been clinically tested and currently available in the market. In this contribution, the recent studies on anti-photoaging properties of extracts and bioactive compounds derived from seaweeds were described and discussed.     

Bioactivities of Lipid Extracts and Complex Lipids from Seaweeds: Current Knowledge and Future Prospects

While complex lipids of seaweeds are known to display important phytochemical properties, their full potential is yet to be explored. This review summarizes the findings of a systematic survey of scientific publications spanning over the years 2000 to January 2021 retrieved from Web of Science (WoS) and Scopus databases to map the state of the art and identify knowledge gaps on the relationship between the complex lipids of seaweeds and their reported bioactivities. Eligible publications (270 in total) were classified in five categories according to the type of studies using seaweeds as raw biomass (category 1); studies using organic extracts (category 2); studies using organic extracts with identified complex lipids (category 3); studies of extracts enriched in isolated groups or classes of complex lipids (category 4); and studies of isolated complex lipids molecular species (category 5), organized by seaweed phyla and reported bioactivities. Studies that identified the molecular composition of these bioactive compounds in detail (29 in total) were selected and described according to their bioactivities (antitumor, anti-inflammatory, antimicrobial, and others). Overall, to date, the value for seaweeds in terms of health and wellness effects were found to be mostly based on empirical knowledge. Although lipids from seaweeds are little explored, the published work showed the potential of lipid extracts, fractions, and complex lipids from seaweeds as functional ingredients for the food and feed, cosmeceutical, and pharmaceutical industries. This knowledge will boost the use of the chemical diversity of seaweeds for innovative value-added products and new biotechnological applications.     

Therapeutic Potential and Nutraceutical Profiling of North Bornean Seaweeds: A Review

Malaysia has a long coastline surrounded by various islands, including North Borneo, that provide a suitable environment for the growth of diverse species of seaweeds. Some of the important North Bornean seaweed species are Kappaphycus alvarezii, Eucheuma denticulatum, Halymenia durvillaei (Rhodophyta), Caulerpa lentillifera, Caulerpa racemosa (Chlorophyta), Dictyota dichotoma and Sargassum polycystum (Ochrophyta). This review aims to highlight the therapeutic potential of North Bornean seaweeds and their nutraceutical profiling. North Bornean seaweeds have demonstrated anti-inflammatory, antioxidant, antimicrobial, anticancer, cardiovascular protective, neuroprotective, renal protective and hepatic protective potentials. The protective roles of the seaweeds might be due to the presence of a wide variety of nutraceuticals, including phthalic anhydride, 3,4-ethylenedioxythiophene, 2-pentylthiophene, furoic acid (K. alvarezii), eicosapentaenoic acid, palmitoleic acid, fucoxanthin, β-carotene (E. denticulatum), eucalyptol, oleic acid, dodecanal, pentadecane (H. durvillaei), canthaxanthin, oleic acid, pentadecanoic acid, eicosane (C. lentillifera), pseudoephedrine, palmitic acid, monocaprin (C. racemosa), dictyohydroperoxide, squalene, fucosterol, saringosterol (D. dichotoma), and lutein, neophytadiene, cholest-4-en-3-one and cis-vaccenic acid (S. polycystum). Extensive studies on the seaweed isolates are highly recommended to understand their bioactivity and mechanisms of action, while highlighting their commercialization potential.     

In Vitro Prebiotic and Anti-Colon Cancer Activities of Agar-Derived Sugars from Red Seaweeds

Numerous health benefits of diets containing red seaweeds or agar-derived sugar mixtures produced by enzymatic or acid hydrolysis of agar have been reported. However, among various agar-derived sugars, the key components that confer health-beneficial effects, such as prebiotic and anti-colon cancer activities, remain unclear. Here, we prepared various agar-derived sugars by multiple enzymatic reactions using an endo-type and an exo-type of β-agarase and a neoagarobiose hydrolase and tested their in vitro prebiotic and anti-colon cancer activities. Among various agar-derived sugars, agarotriose exhibited prebiotic activity that was verified based on the fermentability of agarotriose by probiotic bifidobacteria. Furthermore, we demonstrated the anti-colon cancer activity of 3,6-anhydro-l-galactose, which significantly inhibited the proliferation of human colon cancer cells and induced their apoptosis. Our results provide crucial information regarding the key compounds derived from red seaweeds that confer beneficial health effects, including prebiotic and anti-colon cancer activities, to the host.     

Spirulina Microalgae and Brain Health: A Scoping Review of Experimental and Clinical Evidence

Spirulina microalgae contain a plethora of nutrient and non-nutrient molecules providing brain health benefits. Numerous in vivo evidence has provided support for the brain health potential of spirulina, highlighting antioxidant, anti-inflammatory, and neuroprotective mechanisms. Preliminary clinical studies have also suggested that spirulina can help to reduce mental fatigue, protect the vascular wall of brain vessels from endothelial damage and regulate internal pressure, thus contributing to the prevention and/or mitigating of cerebrovascular conditions. Furthermore, the use of spirulina in malnourished children appears to ameliorate motor, language, and cognitive skills, suggesting a reinforcing role in developmental mechanisms. Evidence of the central effect of spirulina on appetite regulation has also been shown. This review aims to understand the applicative potential of spirulina microalgae in the prevention and mitigation of brain disorders, highlighting the nutritional value of this “superfood”, and providing the current knowledge on relevant molecular mechanisms in the brain associated with its dietary introduction.     

Bioactivity and Applications of Sulphated Polysaccharides from Marine Microalgae

Marine microalgae have been used for a long time as food for humans, such as Arthrospira (formerly, Spirulina), and for animals in aquaculture. The biomass of these microalgae and the compounds they produce have been shown to possess several biological applications with numerous health benefits. The present review puts up-to-date the research on the biological activities and applications of polysaccharides, active biocompounds synthesized by marine unicellular algae, which are, most of the times, released into the surrounding medium (exo- or extracellular polysaccharides, EPS). It goes through the most studied activities of sulphated polysaccharides (sPS) or their derivatives, but also highlights lesser known applications as hypolipidaemic or hypoglycaemic, or as biolubricant agents and drag-reducers. Therefore, the great potentials of sPS from marine microalgae to be used as nutraceuticals, therapeutic agents, cosmetics, or in other areas, such as engineering, are approached in this review.     

An Overview to the Health Benefits of Seaweeds Consumption

Currently, seaweeds are gaining major attention due to the benefits they give to our health. Recent studies demonstrate the high nutritional value of seaweeds and the powerful properties that seaweeds’ bioactive compounds provide. Species of class Phaeophyceae, phylum Rhodophyta and Chlorophyta possess unique compounds with several properties that are potential allies of our health, which make them valuable compounds to be involved in biotechnological applications. In this review, the health benefits given by consumption of seaweeds as whole food or by assumption of bioactive compounds trough natural drugs are highlighted. The use of seaweeds in agriculture is also highlighted, as they assure soils and crops free from chemicals; thus, it is advantageous for our health. The addition of seaweed extracts in food, nutraceutical, pharmaceutical and industrial companies will enhance the production and consumption/usage of seaweed-based products. Therefore, there is the need to implement the research on seaweeds, with the aim to identify more bioactive compounds, which may assure benefits to human and animal health.     

Marine carotenoids: biological functions and commercial applications

Carotenoids are the most common pigments in nature and are synthesized by all photosynthetic organisms and fungi. Carotenoids are considered key molecules for life. Light capture, photosynthesis photoprotection, excess light dissipation and quenching of singlet oxygen are among key biological functions of carotenoids relevant for life on earth. Biological properties of carotenoids allow for a wide range of commercial applications. Indeed, recent interest in the carotenoids has been mainly for their nutraceutical properties. A large number of scientific studies have confirmed the benefits of carotenoids to health and their use for this purpose is growing rapidly. In addition, carotenoids have traditionally been used in food and animal feed for their color properties. Carotenoids are also known to improve consumer perception of quality; an example is the addition of carotenoids to fish feed to impart color to farmed salmon.     

Antifungal and Larvicidal Activities of Phlorotannins from Brown Seaweeds

Phlorotannins are secondary metabolites produced by brown seaweeds with antiviral, antibacterial, antifungal, and larvicidal activities. Phlorotannins’ structures are formed by dibenzodioxin, ether and phenyl, ether, or phenyl linkages. The polymerization of phlorotannins is used to classify and characterize. The structural diversity of phlorotannins grows as polymerization increases. They have been characterized extensively with respect to chemical properties and functionality. However, review papers of the biological activities of phlorotannins have focused on their antibacterial and antiviral effects, and reviews of their broad antifungal and larvicidal effects are lacking. Accordingly, evidence for the effectiveness of phlorotannins as antifungal and larvicidal agents is discussed in this review. Online databases (ScienceDirect, PubMed, MEDLINE, and Web of Science) were used to identify relevant articles. In total, 11 articles were retrieved after duplicates were removed and exclusion criteria were applied. Phlorotannins from brown seaweeds show antifungal activity against dermal and plant fungi, and larvicidal activity against mosquitos and marine invertebrate larvae. However, further studies of the biological activity of phlorotannins against fungal and parasitic infections in aquaculture fish, livestock, and companion animals are needed for systematic analyses of their effectiveness. The research described in this review emphasizes the potential applications of phlorotannins as pharmaceutical, functional food, pesticide, and antifouling agents.     

Impact of Phlorotannin Extracts from Fucus vesiculosus on Human Gut Microbiota

Recent studies indicate that plant polyphenols could be pointed as potential prebiotic candidates since they may interact with the gut microbiota, stimulating its growth and the production of metabolites. However, little is known about the fate of brown seaweeds’ phlorotannins during their passage throughout the gastrointestinal tract. This work aimed to evaluate the stability and bioaccessibility of Fucus vesiculosus phlorotannins after being submitted to a simulated digestive process, as well as their possible modulatory effects on gut microbiota and short-chain fatty acids production following a fermentation procedure using fecal inoculates to mimic the conditions of the large intestine. The stability of phlorotannins throughout the gastrointestinal tract was reduced, with a bioaccessibility index between 2 and 14%. Moreover, slight alterations in the growth of certain commensal bacteria were noticed, with Enterococcus spp. being the most enhanced group. Likewise, F. vesiculosus phlorotannins displayed striking capacity to enhance the levels of propionate and butyrate, which are two important short-chain fatty acids known for their role in intestinal homeostasis. In summary, this work provides valuable information regarding the behavior of F. vesiculosus phlorotannins along the gastrointestinal tract, presenting clear evidence that these compounds can positively contribute to the maintenance of a healthy gastrointestinal condition.     

Alternative Sources of n-3 Long-Chain Polyunsaturated Fatty Acids in Marine Microalgae

The main source of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in human nutrition is currently seafood, especially oily fish. Nonetheless, due to cultural or individual preferences, convenience, geographic location, or awareness of risks associated to fatty fish consumption, the intake of fatty fish is far from supplying the recommended dietary levels. The end result observed in most western countries is not only a low supply of n-3 LC-PUFA, but also an unbalance towards the intake of n-6 fatty acids, resulting mostly from the consumption of vegetable oils. Awareness of the benefits of LC-PUFA in human health has led to the use of fish oils as food supplements. However, there is a need to explore alternatives sources of LC-PUFA, especially those of microbial origin. Microalgae species with potential to accumulate lipids in high amounts and to present elevated levels of n-3 LC-PUFA are known in marine phytoplankton. This review focuses on sources of n-3 LC-PUFA, namely eicosapentaenoic and docosahexaenoic acids, in marine microalgae, as alternatives to fish oils. Based on current literature, examples of marketed products and potentially new species for commercial exploitation are presented.     

Enhancing Bioproducts in Seaweeds via Sustainable Aquaculture: Antioxidant and Sun-Protection Compounds

Marine macroalgae are considered an untapped source of healthy natural metabolites and their market demand is rapidly increasing. Intertidal macroalgae present chemical defense mechanisms that enable them to thrive under changing environmental conditions. These intracellular chemicals include compounds that can be used for human benefit. The aim of this study was to test cultivation protocols that direct seaweed metabolic responses to enhance the production of target antioxidant and photoprotective biomaterials. We present an original integrated multi-trophic aquaculture (IMTA) design, based on a two-phase cultivation plan, in which three seaweed species were initially fed by fish effluents, and subsequently exposed to various abiotic stresses, namely, high irradiance, nutrient starvation, and high salinity. The combined effect of the IMTA’s high nutrient concentrations and/or followed by the abiotic stressors enhanced the seaweeds’ content of mycosporine-like amino acids (MAAs) by 2.3-fold, phenolic compounds by 1.4-fold, and their antioxidant capacity by 1.8-fold. The Sun Protection Factor (SPF) rose by 2.7-fold, and the chlorophyll and phycobiliprotein synthesis was stimulated dramatically by an order of magnitude. Our integrated cultivation system design offers a sustainable approach, with the potential to be adopted by emerging industries for food and health applications.     

Sulphated Polysaccharides from Ulva clathrata and Cladosiphon okamuranus Seaweeds both Inhibit Viral Attachment/Entry and Cell-Cell Fusion,in NDV Infection

Sulphated polysaccharides (SP) extracted from seaweeds have antiviral properties and are much less cytotoxic than conventional drugs, but little is known about their mode of action. Combination antiviral chemotherapy may offer advantages over single agent therapy, increasing efficiency, potency and delaying the emergence of resistant virus. The paramyxoviridae family includes pathogens causing morbidity and mortality worldwide in humans and animals, such as the Newcastle Disease Virus (NDV) in poultry. This study aims at determining the antiviral activity and mechanism of action in vitro of an ulvan (SP from the green seaweed Ulva clathrata), and of its mixture with a fucoidan (SP from Cladosiphon okamuranus), against La Sota NDV strain. The ulvan antiviral activity was tested using syncytia formation, exhibiting an IC₅₀ of 0.1 μg/mL; ulvan had a better anti cell-cell spread effect than that previously shown for fucoidan, and inhibited cell-cell fusion via a direct effect on the F0 protein, but did not show any virucidal effect. The mixture of ulvan and fucoidan showed a greater anti-spread effect than SPs alone, but ulvan antagonizes the effect of fucoidan on the viral attachment/entry. Both SPs may be promising antivirals against paramyxovirus infection but their mixture has no clear synergistic advantage.     

Carotenoid Production from Microalgae: Biosynthesis,Salinity Responses and Novel Biotechnologies

Microalgae are excellent biological factories for high-value products and contain biofunctional carotenoids. Carotenoids are a group of natural pigments with high value in social production and human health. They have been widely used in food additives, pharmaceutics and cosmetics. Astaxanthin, β-carotene and lutein are currently the three carotenoids with the largest market share. Meanwhile, other less studied pigments, such as fucoxanthin and zeaxanthin, also exist in microalgae and have great biofunctional potentials. Since carotenoid accumulation is related to environments and cultivation of microalgae in seawater is a difficult biotechnological problem, the contributions of salt stress on carotenoid accumulation in microalgae need to be revealed for large-scale production. This review comprehensively summarizes the carotenoid biosynthesis and salinity responses of microalgae. Applications of salt stress to induce carotenoid accumulation, potentials of the Internet of Things in microalgae cultivation and future aspects for seawater cultivation are also discussed. As the global market share of carotenoids is still ascending, large-scale, economical and intelligent biotechnologies for carotenoid production play vital roles in the future microalgal economy.     

Exopolysaccharides from Microalgae and Cyanobacteria: Diversity of Strains,Production Strategies,and Applications

Microalgae and cyanobacteria are photosynthetic organisms that can produce/accumulate biomolecules with industrial interest. Among these molecules, EPSs are macromolecular polysaccharidic compounds that present biological activities and physico-chemical properties, allowing to consider their valorization in diverse commercial markets, such as cosmetic, therapeutic, nutraceutic, or hydrocolloids areas. The number of microalgae and cyanobacteria strains described to produce such EPSs has increased in recent years as, among the 256 producing strains gathered in this review, 86 were published in the last 10 years (~33%). Moreover, with the rise of research on microalgae EPSs, a variety of monosaccharides compositions have been discovered, highlighting the versatility of these organisms. If some production strategies can be applied to increase EPS production yields, it appears that case by case studies are needed to promote EPS synthesis by a strain, as many responses exist. This paper proposes an up-to-date state of the art of the diversity of microalgae and cyanobacteria EPS-producing strains, associated to the variability of compositions. The strategies for the production and extraction of the polymers are also discussed. Finally, an overview of the biological activities and physico-chemical properties allow one to consider their use on several commercial markets.     

Microalgae as Sustainable Bio-Factories of Healthy Lipids: Evaluating Fatty Acid Content and Antioxidant Activity

The demand for sustainable and environmentally friendly food sources and food ingredients is increasing, and microalgae are promoted as a sustainable source of essential and bioactive lipids, with high levels of omega-3 fatty acids (ω-3 FA), comparable to those of fish. However, most FA screening studies on algae are scattered or use different methodologies, preventing a true comparison of its content between microalgae. In this work, we used gas-chromatography mass-spectrometry (GC-MS) to characterize the FA profile of seven different commercial microalgae with biotechnological applications (Chlorella vulgaris, Chlorococcum amblystomatis, Scenedesmus obliquus, Tetraselmis chui, Phaeodactylum tricornutum, Spirulina sp., and Nannochloropsis oceanica). Screening for antioxidant activity was also performed to understand the relationship between FA profile and bioactivity. Microalgae exhibited specific FA profiles with a different composition, namely in the ω-3 FA profile, but with species of the same phylum showing similar tendencies. The different lipid extracts showed similar antioxidant activities, but with a low activity of the extracts of Nannochloropsis oceanica. Overall, this study provides a direct comparison of FA profiles between microalgae species, supporting the role of these species as alternative, sustainable, and healthy sources of essential lipids.     

Sulfated Glucan from the Green Seaweed Caulerpa sertularioides Inhibits Adipogenesis through Suppression of Adipogenic and Lipogenic Key Factors

Sulfated polysaccharides (SPS) from seaweeds have great biochemical and biotechnological potential. This study aimed to investigate the effect of SPS isolated from the seaweed Caulerpa sertularioides on adipogenic differentiation as a possible alternative treatment for obesity. The SPS-rich extract from the seaweed C. sertularioides was fractioned into three SPS-rich fractions (F0.5; F0.9; and F1.8) chemically characterized. Among these four samples, only F0.9 showed a significant inhibitory effect on adipogenesis of 3T3-L1 preadipocytes. Ten SPS-rich fractions were isolated from F0.9 through ion-exchange chromatography. However, only the fraction (CS0.2) containing a sulfated glucan was able to inhibit adipogenesis. CS0.2 reduces lipid accumulation and inhibits the expression of key adipogenic (PPARγ, C/EBPβ, and C/EBPα) and lipogenic markers (SREBP-1c, Fabp4, and CD36). The data points to the potential of sulfated glucan from C. sertularioides for the development of functional approaches in obesity management.     

Improving Microalgae Research and Marketing in the European Atlantic Area: Analysis of Major Gaps and Barriers Limiting Sector Development

Microalgae and cyanobacteria represent a diverse renewable resource with significant potential for the industrial production of goods and services with high added value. However, scientific, technical/technological, legislative and market gaps and barriers still limit the growth of these markets in Europe and the number of exploited species. We conducted an in-depth survey of European microalgae researchers, experts and stakeholders to identify these limitations and to discuss strategies, recommendations and guidelines to overcome these barriers. Here, we present the findings of this study which detail the main promising markets for microalgae and cyanobacteria in the coming decades, an updated SWOT analysis of the sector, the current opportunities, limitations, risks and threats for microalgae research and market sectors in Europe, a traffic light analysis for a quick assessment of market opportunities for each microalgae sector and detailed recommendations/guidelines for overcoming the scientific, technical/technological, legislative and market gaps and barriers.