Gut Microbiome

The availability of host and dietary carbohydrates in the gastrointestinal (GI) tract plays a key role in shaping the structure-function of the microbiota. In particular, some gut bacteria have the ability to forage on glycans provided by the mucus layer covering the GI tract. The O-glycan structures present in mucin are diverse and complex, consisting predominantly of core 1-4 mucin-type O-glycans containing α- and β- linked N-acetyl-galactosamine, galactose and N-acetyl-glucosamine. These core structures are further elongated and frequently modified by fucose and sialic acid sugar residues via α1,2/3/4 and α2,3/6 linkages, respectively. The ability to metabolize these mucin O-linked oligosaccharides is likely to be a key factor in determining which bacterial species colonize the mucosal surface. Due to their proximity to the immune system, mucin-degrading bacteria are in a prime location to influence the host response. However, despite the growing number of bacterial genome sequences available from mucin degraders, our knowledge on the structural requirements for mucin degradation by gut bacteria remains fragmented. This is largely due to the limited number of functionally characterized enzymes and the lack of studies correlating the specificity of these enzymes with the ability of the strain to degrade and utilize mucin and mucin glycans. This review focuses on recent findings unraveling the molecular strategies used by mucin-degrading bacteria to utilize host glycans, adapt to the mucosal environment, and influence human health.

Human gut microbiome is defined as the gene complement of the gut microbial community, measured via laboratory metagenomic techniques. It includes bacteriome, virome and mycobiome, which represent, respectively, the assemblages of bacteria, viruses and fungi, living in the human gut. Gut microbiota function as a living " organ " that interacts with the gastro-intestinal environment, provides nutrients and vitamins to the organism and transduces hormonal messages, essentially influencing the main metabolic pathways, including drug metabolism. A clear association between gut, and glucose metabolism disorders has recently emerged. Medications acting on glucose absorption in the gut, or enhancing gut hormone activity are already extensively employed in the therapy of diabetes. Moreover, the gut is characterized by immune, and autonomous neuronal features, which play a critical role in maintaining glucose metabolism homeostasis. Gut microbes respond to neuroendocrine, and immune biochemical messages, affecting the health, and behavior of the host. There is vast heterogeneity in the studies included in this review, hence a meta-analysis, or a systematic review were not applicable. In this article, we attempt to reveal the interplay between human gut microbiota physiology, and hyperglycemic states, synthesizing, and interpreting findings from human studies.

The concept of a holobiont, a host organism and its associated microbial communities, encapsulates the vital role the microbiome plays in the normal functioning of its host. Parasitic infections can disrupt this relationship, leading to dysbiosis. However, it is increasingly recognized that multicellular parasites are themselves holobionts. Intestinal parasites share space with the host gut microbiome, creating a system of nested microbiomes within the primary host. However, how the parasite, as a holobiont, interacts with the host holobiont remains unclear, as do the consequences of these interactions for host health. Here, we used 16S amplicon and shotgun metagenomics sequencing to characterize the microbiome of the intestinal cestode Eubothrium and its effect on the gut microbiome of its primary host, Atlantic salmon. Our results indicate that cestode infection is associated with salmon gut dysbiosis by acting as a selective force benefiting putative pathogens and potentially introducing novel bacterial species to the host. Our results suggest that parasitic cestodes may themselves be holobionts nested within the microbial community of their holobiont host, emphasizing the importance of also considering microbes associated with parasites when studying intestinal parasitic infections.

Ильясов, Р.А., Марсова, М.В., Ковтун, А.С., Ватлин, А.А., Юнес, Р.А., Гайфуллина, Л.Р., Каскинова, М.Д., Николенко, А.Г., Квон, Х.В., Даниленко, В.Н., 2021. Генетические аспекты сохранения популяций медоносной пчелы Apis mellifera. In: Еськов, Е.К. ed. 5-ая Международная научно-практическая конференция "Пчеловодство холодного и умеренного климата". ФГБОУ ВО «Российский государственный аграрный заочный университет», Москва-Псков, pp. 38-47.
Ilyasov, R.A., Marsova, M.V., Kovtun, A.S., Vatlin, A.A., Younes, R.A., Gaifullina, L.R., Kaskinova, M.D., Nikolenko, A.G., Kwon, H.W., Danilenko, V.N., 2021. Genetic aspects of the conservation of populations of the honeybee Apis mellifera. In: Eskov, E.K. ed. The 5th International Scientific and Practical Conference "Cold and moderate climate beekeeping". Ministry of Agriculture of the Russian Federation "Russian State Agrarian Correspondence University" Moscow-Pskov, pp. 38-47.
Аннотация. Под влиянием факторов окружающей среды и деятельности человека изоляция географических подвидов была нарушена и локальным генофондам подвидов стала угрожать опасность интрогрессивной гибридизации. Идентификация подвидов пчел молекулярно-генетическими методами позволяет снизить процесс гибридизации подвидов. Применение генетических методов в изучении популяции пчел позволяет оценить основные популяционно-генетические характеристики, такие как аллельное и генетическое разнообразие, инбридинг, эффективный размер популяции, эффекты бутылочного горлышка. Знания генетических показателей популяции позволят разработать эффективные стратегии сохранения генофонда подвидов пчел. Показано, что микробиом кишечника вовлечен в модуляцию практически всех систем организма медоносной пчелы и играет важную роль в иммунитете и адаптации пчел к условиям среды обитания. Комплексные исследования генома и метагенома микробиома кишечника пчел могут открыть новые перспективы в консервативной генетике популяций подвидов пчел.
Abstract. Under the influence of environmental factors and human activities, the isolation of geographic subspecies was disrupted and the local gene pools of the subspecies were threatened by the danger of introgressive hybridization. The identification of subspecies of bees by molecular genetic methods makes it possible to reduce the process of hybridization of the subspecies. The use of genetic methods in the study of the population of bees makes it possible to assess the main population genetic characteristics, such as allelic and genetic diversity, inbreeding, effective population size, and bottleneck effects. Knowledge of the genetic parameters of the population will make it possible to develop effective strategies for preserving the gene pool of bee subspecies. It has been shown that the gut microbiome is involved in the modulation of almost all systems of the honeybee and plays an important role in the immunity and adaptation of bees to environmental conditions. Comprehensive studies of the genome and metagenome of the gut microbiome of bees may open up new perspectives in the conservative genetics of populations of subspecies of bees.

The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastroin-testinal tract communicates with the central nervous system through the gut–brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecul...

Dietary fiber (DF) was considered an antinutritional factor due to its adverse effects on feed intake and nutrient digestibility. However, with increasing evidence, scientists have found that DF has enormous impacts on the gastrointestinal tract (GIT) development, digestive physiology, including nutrient digestion, fermentation, and absorption processes of poultry. It may help maintain the small and large intestine's integrity by strengthening mucosal structure and functions and increasing the population and diversity of commensal bacteria in the GIT. Increasing DF content benefits digestive physiology by stimulating GIT development and enzyme production. And the inclusion of fiber at a moderate level in diets also alters poultry growth performance. It improves gut health by modulating beneficial microbiota in the large intestine and enhancing immune functions. However, determining the source, type, form, and level of DF inclusion is of utmost importance to achieve the above-noted benefits. This paper critically reviews the available information on dietary fibers used in poultry and their effects on nutrient utilization, GIT development, gut health, and poultry performance. Understanding these functions will help develop nutrition programs using proper DF at an appropriate inclusion level that will ultimately lead to enhanced DF utilization, overall health, and improved poultry growth performance. Thus, this review will help researchers and industry identify the sources, type, form, and amount of DF to be used in poultry nutrition for healthy, cost-effective, and eco-friendly poultry production.

The study of the human commensal micro-flora has recently regained the interest of the scientific community, particularly after the development of genomics and bio-informatics. The genes of the microbes found in the various different cavities of the human organism are collectively called the human microbiome (HM). This is a complex system, which is estimated to consist of approximately 1014 bacterial cells, thus being 10 times larger than the total of human cells. Almost 400−500 different types of microbes form the intestinal flora of the HM. The commensal bacteria in the gut microbiota interact with each other and with the host immune system, contributing to the homeostasis of the organism. The intestinal microbiome has been shown to differ among individuals of the same sex, between sexes and between individuals of different ages. Εach individual human can be characterized by his/her own intestinal microbial fingerprint, which may be useful in the future for individualized medicine. Alteration in the composition and function of the commensal gut  microbiota has been associated with complex diseases such as inflammatory bowel
diseases (IBD), colorectal cancer, allergies and obesity. Manipulation of the gut microbiota by fecal microbiota transplantation
is an effective and safe treatment of IBD and infection with C. difficile, but the use of pre- and pro-biotics
for the manipulation of microbiota should be reconsidered in the light of the new information now available. This is
a review of recent findings concerning the role of the enteric HM in the development of the immune system, and its
connection to gut-related and non-gastroenterological diseases.

Turkey is a home country for a good number of fermented beverages derived from milk, cereals, fruits and vegetables, and several studies have reported the probiotic potentiality of these beverages. Probiotics, otherwise known as beneficial microorganisms possess the ability to exert antimicrobial effects, which is one of the most important selection criteria for their use in commercial products. In the current study, the antimicrobial activities of potential probiotic bacteria isolated from five fermented traditional Turkish beverages (boza, kefir, ayran, shalgam juice and hardaliye) were evaluated. The bacterial isolates were morphologically characterized and genotypically identified by 16S rRNA gene sequence analysis. The antimicrobial effects of the isolates against selected human pathogens were assessed using spot-on-the-lawn and agar well diffusion assays. Eighteen of the twenty-two strains displayed varying degrees of antagonism against the tested pathogens. Amongst the isolat...

Several species of large millipedes are kept as pets and generally called giant millipedes or giant African
millipedes. There is often confusion over the species names of these millipedes due to difficulties with their exact
determination. Their large body size and the relative ease with which they can be kept under laboratory conditions
means they are suitable subjects for experimental investigations. Archispirostreptus gigas (Peters, 1855), the
giant African millipede, is one of the largest species, growing up to 32 cm in body length. It is widespread from
Mozambique to Kenya, mainly along the east coast of Africa rather than further inland, occurring in tropical and
arid forest as well as savanna. A short review of different aspects of the conditions required for breeding it in
the laboratory, its ontogeny and use in ecophysiological and physiological studies is presented for it and other
representatives of the order Spirostreptida. Spirostreptid millipedes are recommended as model species for studies on
chemical ecology, parasitology, microbial ecology of digestive tract, embryology and postembryonal development,
biochemistry and physiological mechanisms, including digestion, metabolic physiology and others.

In this review we focus on the revision of the prebiotic concept in the context of the new metagenomic era. Functional metagenomic data provided by the Human Microbiome Project are revolutionizing the view of the symbiotic relationship between the intestinal microbiota and the human host. A deeper knowledge of the mechanisms that govern the dynamic interplay between diet, intestinal microbiota and host nutrition opens the way to better information on the prebiotic structure-function relationships, tailoring prebiotic formula into specific health attributes. On the other hand, functional genomic studies of the sourdough microbial communities allow to scan the environmental variability to identify novel metabolic traits for the biosynthesis of new potential prebiotic molecules. The integration of the functional analyses provided by the massive sequencing of bacterial genomes and metagenomes will allow the rational production of a desired prebiotic molecule with specific functional pro...

Prevotella copri is a common inhabitant of the human gut. Interest in P. copri has gathered pace due to conflicting reports on whether it is beneficial or detrimental to health. In a cross-continent meta-analysis exploiting >6,500 available metagenomes supported by new isolate sequencing and recovery of high-quality genomes from metagenomes, we obtained >1,000 P. copri genomes. This 100-fold increase over existing isolate genomes allowed the genetic and global population structure of P. copri to be explored at an unprecedented depth. We demonstrate P. copri is not a monotypic species, but encompasses four distinct clades (>10% inter-clade vs. <4% intra-clade average single nucleotide variants) for which we propose the name P. copri complex, comprising clades A, B, C and D. We show the complex is near ubiquitous in non-Westernised populations (95.4% versus 29.6% in Westernised populations), where all four clades are typically co-present within an individual (61.6% of the ...

Purpose: It has been demonstrated that hydrogen gas and hydrogen-rich water may act as a therapeutic antioxidant. Hydrogen gas produced by intestinal fermentation is believed to have some preventive effects on age-related diseases. This study was performed to determine whether intestinal production of hydrogen gas could be associated with longevity.
Methods: The hydrogen gas concentrations in the breath, reflecting the intestinal production of hydrogen gas, were measured by a portable breath hydrogen analyzer in twenty-six centenarians who were local residents (6 men, 20 women; age, 102 (2) years (mean (SD)) and 16 offspring (7 men, 9 women; 70 (5) years) who lived in the same household. For comparison, the breath hydrogen gas concentrations were also measured in 14 healthy controls (8 men, 6 women; 37.3 (17.4) years) and 15 elderly people with type 2 diabetes (4 men, 11 women; 79 (6) years).
Results: The hydrogen concentrations in the centenarians (59.4 (62.6) ppm) were significantly (p<0.05) higher than those in the healthy controls (17.7 (19.6) ppm) and in the elderly diabetic patients (23.2 (19.0) ppm), but there was no significant difference between the centenarians and their offspring, living in the same home (37.8 (27.2) ppm).
Conclusion: Increased intestinal production of hydrogen gas might contribute to longevity in Japanese centenarians, and it is presumably related to the diet and gut microbiota.

This brief ebook (https://www.amazon.com/dp/B075LTXYNB) substantiates the "biological plausibility" that gastrointestinal dysbiosis contributes significantly to the autistic phenotype. The first section is an edited, cited and embellished transcript from a post-graduate continuing medical education (CME) presentation; the second section provides additional citations and justification regarding treatment and also exploring a possible interconnection between vaccination and the induction of gastrointestinal dysbiosis.

A B S T R A C T Several lines of evidence suggest that brain function and behaviour are influenced by microbial metabolites. Key products of the microbiota are short-chain fatty acids (SCFAs), including butyric acid. Butyrate is a functionally versatile molecule that is produced in the mammalian gut by fermentation of dietary fibre and is enriched in butter and other dairy products. Butyrate along with other fermentation-derived SCFAs (e.g. acetate, propionate) and the structurally related ketone bodies (e.g. acetoacetate and D-β-hydroxybutyrate) show promising effects in various diseases including obesity, diabetes, inflammatory (bowel) diseases, and colorectal cancer as well as neurological disorders. Indeed, it is clear that host energy metabolism and immune functions critically depend on butyrate as a potent regulator, highlighting butyrate as a key mediator of host-microbe crosstalk. In addition to specific receptors (GPR43/FFAR2; GPR41/FFAR3; GPR109a/HCAR2) and transporters (MCT1/SLC16A1; SMCT1/SLC5A8), its effects are mediated by utilisation as an energy source via the β-oxidation pathway and as an inhibitor of histone deacetylases (HDACs), promoting histone acetylation and stimulation of gene expression in host cells. The latter has also led to the use of butyrate as an experimental drug in models for neu-rological disorders ranging from depression to neurodegenerative diseases and cognitive impairment. Here we provide a critical review of the literature on butyrate and its effects on multiple aspects of host physiology with a focus on brain function and behaviour. We find fundamental differences in natural butyrate at physiological concentrations and its use as a neuropharmacological agent at rather high, supraphysiological doses in brain research. Finally, we hypothesise that butyrate and other volatile SCFAs produced by microbes may be involved in regulating the impact of the microbiome on behaviour including social communication.

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome.

The amygdala is a key brain region that is critically involved in the processing and expression of anxiety and fear-related signals. In parallel, a growing number of preclinical and human studies have implicated the microbiome–gut–brain in regulating anxiety and stress-related responses. However, the role of the microbiome in fear-related behaviours is unclear. To this end we investigated the importance of the host microbiome on amygdala-dependent behavioural readouts using the cued fear conditioning paradigm. We also assessed changes in neuronal transcription and post-transcriptional regulation in the amygdala of naive and stimulated germ-free (GF) mice, using a genome-wide transcriptome profiling approach. Our results reveal that GF mice display reduced freezing during the cued memory retention test. Moreover, we demonstrate that under baseline conditions, GF mice display altered transcriptional profile with a marked increase in immediate-early genes (for example, Fos, Egr2, Fosb, Arc) as well as genes implicated in neural activity, synaptic transmission and nervous system development. We also found a predicted interaction between mRNA and specific microRNAs that are differentially regulated in GF mice. Interestingly, colonized GF mice (ex-GF) were behaviourally comparable to conventionally raised (CON) mice. Together, our data demonstrates a unique transcriptional response in GF animals, likely because of already elevated levels of immediate-early gene expression and the potentially underlying neuronal hyperactivity that in turn primes the amygdala for a different transcriptional response. Thus, we demonstrate for what is to our knowledge the first time that the presence of the host microbiome is crucial for the appropriate behavioural response during amygdala-dependent memory retention.

It has become increasingly clear that there is a vast array of microorganisms on and in the human body, known collectively as the human microbiome. Our microbiomes are extraordinarily complex, and this complexity has been linked to human health and well-being. Given the complexity and importance of our microbiomes, we struggle with how to think about them. There is a long list of competing metaphors that we use to refer to our microbiomes, including as an "organ" containing our "second genome," as a "symbiont" in the human "holobiont," and as an ecological "community" in the human "ecosystem," among others. Each of these makes different assumptions about the fundamental biology of the human-microbe system, with important implications for how we choose to study microbiomes, and the therapies we envision for correcting microbiome-linked disorders. We believe that it is time to move beyond metaphors, and we propose a scientifically pluralist approach that focuses on characterizing fundamental biological properties of microbiomes such as heritability, transmission mode, rates of dispersal rates, and strength of local selection. Such an approach will allow us to break out of the confines of narrow conceptual frameworks, and to guide the exploration of our complexity as chimeric beings.

Glyphosate, the active ingredient in Roundup ® , is the most popular herbicide used worldwide. The industry asserts it is minimally toxic to humans, but here we argue otherwise. Residues are found in the main foods of the Western diet, comprised primarily of sugar, corn, soy and wheat. Glyphosate's inhibition of cytochrome P450 (CYP) enzymes is an overlooked component of its toxicity to mammals. CYP enzymes play crucial roles in biology, one of which is to detoxify xenobiotics. Thus, glyphosate enhances the damaging effects of other food borne chemical residues and environmental toxins. Negative impact on the body is insidious and manifests slowly over time as inflammation damages cellular systems throughout the body. Here, we show how interference with CYP enzymes acts synergistically with disruption of the biosynthesis of aromatic amino acids by gut bacteria, as well as impairment in serum sulfate transport. Consequences are most of the diseases and conditions associated with a Western diet, which include gastrointestinal disorders, obesity, diabetes, heart disease, depression, autism, infertility, cancer and Alzheimer's disease. We explain the documented effects of glyphosate and its ability to induce disease, and we show that glyphosate is the "textbook example" of exogenous semiotic entropy: the disruption of homeostasis by environmental toxins.

Даниленко, В.Н., Ильясов, Р.A., Юнес, Р.А., 2021. Микробиом. Фармабиотики. Нутригеномика. Перспективы использования в постковидную эру. In: Кильчевский, А.В. ed. Жебраковские чтения X. Преобразование геномов. Институт генетики и цитологии Национальной академии наук Беларуси, Минск, pp. 1-44. isbn: 978-985-90552-4-9.
Danilenko, V.N., Ilyasov, R., Younes, R.A., 2021. Microbiome. Pharmabiotics. Nutrigenomics. Prospects for use in the post-covid era. In: Kilchevsky, A.V. ed. Zhebrakovskie readings X. Transformation of genomes. Institute of Genetics and Cytology of the National Academy of Sciences of Belarus, Minsk, pp. 1-44. isbn: 978-985-90552-4-9.
Резюме. Сегодня всем известны этапы разработки антибактериальных препаратов, включая антибиотики, успехи и проблемы их применения в медицине. Первоначально усилиями ученых всего мира были созданы антибиотики на основе природных продуцентов почвенного происхождения. Широкомасштабное и, порой, нерациональное применение антибактериальных препаратов способствовало появлению и широкому распространению патогенов, устойчивых к большинству антибиотиков. Такая же ситуация складывалась и в области разработки противовирусных и иммуномодулирующих препаратов. Стало очевидным, что человек проигрывает гонку бактериям. Появилась необходимость в создании новых подходов и парадигм в разработке технологий и выбора источников лекарственных средств, в первую очередь противоинфекционных. Успехи последнего десятилетия в области изучения микробиоты человека открыли перед нами много возможностей. Современные знания о структуре и функциях кишечной микробиоты человека и концептуальное объединение знаний о комменсальных микроорганизмах, включая пробиотические, полученные молекулярно-генетическими, транскриптомными, протеомными и метаболомными методами, позволили сформировать понятие фармабиотиков. Создание фармабиотиков на основе микроорганизмов, населяющих различные полости тела человека, включая кишечник, является новым, интенсивно развивающимся направлением фармакологической науки. Поставленные задачи в этой области могут быть решены при условии комплексного решения ряда фундаментальных задач, обеспечивающих создание эффективных и безопасных фармпрепаратов и ингредиентов для них. Пандемия COVID-19 заставила ученых и правительства всех стран мобилизовать усилия для создания новых противовирусных препаратов, изучения механизмов протекания вирусных инфекций и функционирования иммунной и антиоксидантной систем человека. Роль микробиома и фармабиотиков, как селективных модуляторов иммунной системы человека, в первую очередь клеточного иммунитета, а также антиоксидантной системы становится все более очевидной. В течение последнего десятилетия в лаборатории генетики микроорганизмов ИОГен РАН интенсивно проводятся исследования микробиома кишечника человека и разработки препаратов на его основе с нейромодулирующей, иммуномодулирующей и антиоксидантной активностью.
Abstract. Today, everyone knows the stages in the development of antibacterial drugs, including antibiotics, and the successes and problems of their use in medicine. Initially, through the efforts of scientists around the world, antibiotics were created based on the natural producers of soil. Large-scale and irrational use of antibacterial drugs has contributed to the emergence and widespread distribution of pathogens resistant to most antibiotics. The same situation appeared in the development of antiviral and immunomodulatory drugs. It is obvious that humanity is losing the struggle against bacteria. There is a need to create new approaches and paradigms in the development of technologies and the selection of sources of drugs, primarily anti-infectious drugs. The successes of the last decade in the study of the human microbiota have opened up many opportunities for us. Modern knowledge about the structure and functions of the human intestinal microbiota and the conceptual combination of knowledge about commensal microorganisms, including probiotic ones, obtained by molecular genetic, transcriptomic, proteomic, and metabolic methods, allowed us to form the concept of pharmabiotics. The creation of pharmabiotics based on microorganisms inhabiting various cavities of the human body, including the intestine, is a new, intensively developing area of pharmacological science. The tasks set in this area can be solved by ensuring the creation of effective and safe pharmaceuticals and ingredients for them. The COVID-19 pandemic has forced scientists and governments of all countries to mobilize efforts to create new antiviral drugs and study the mechanisms of viral infections and the functioning of the human immune and antioxidant systems. The role of the microbiome and pharmabiotics as selective modulators of the human immune system, primarily cellular immunity, as well as the antioxidant system, is becoming more and more evident. Over the past decade, the laboratory of genetics of microorganisms of the Institute of Genetics of the Russian Academy of Sciences has been intensively conducting research on the human intestinal microbiome and the development of drugs based on it with neuromodulatory, immunomodulatory, and antioxidant activity.

In this review we focus on the revision of the prebiotic concept in the context of the new metagenomic era. Functional metagenomic data provided by the Human Microbiome Project are revolutionizing the view of the symbiotic relationship between the intestinal microbiota and the human host. A deeper knowledge of the mechanisms that govern the dynamic interplay between diet, intestinal microbiota and host nutrition opens the way to better information on the prebiotic structure-function relationships, tailoring prebiotic formula into specific health attributes. On the other hand, functional genomic studies of the sourdough microbial communities allow to scan the environmental variability to identify novel metabolic traits for the biosynthesis of new potential prebiotic molecules. The integration of the functional analyses provided by the massive sequencing of bacterial genomes and metagenomes will allow the rational production of a desired prebiotic molecule with specific functional pro...

Abstract
Background: Deficiency in B-cell development is the most frequent of primary immunodeficiency disorders (PIDD), characterised by complications, making diagnoses and treatment challenging. Patients receive intravenous immunoglobulin (IGIV) and micronutrient supplementation to improve prognosis, with likely changes in biomarkers. Associations were sought between medico-clinical parameters, serum exosomal miRNA and the gut microbiome in patients with PIDD after intravenous immunoglobulin (IGIV) and micronutrient supplementation. Methodology: Ethical approval was granted. Retrospective analysis of data from PIDD (n=48), which included phenotypic classification, inflammatory markers, age at presentation and vitamin D levels, on a subset (n=27). Intervention studies (n=10) of serum exosomal microRNA expression and the gut microbiome were done pre-/post-IGIV and -vitamin (A, E, B, and D) supplementation. Results: Vitamin D deficiency was apparent in patients, compared to reference ranges. Comparisons between patients with PIDD with no complications, as opposed to those with bronchiectasis and/or allergy, showed comparable vitamin D levels (p>0.05). Elevated CRP and lower IgG levels were apparent in patients with bronchiectasis and allergy complication (p<0.05). White blood cell (WBC) counts were higher in patients without complications (p=0.03), perhaps indicating a lower infection rate in this group. Bronchiectasis was higher in patients diagnosed at paediatric age (<14 years; 11 out of 12; 91.7%) compared to adults (9 out of 24; 37.5%) (p=0.002). Smoking was not associated with an increased rate of complications, but males appeared more prone to bronchiectasis (p=0.003). Exosomal miR showed up-regulation in 2 miRNAs (hsa-miR-122-5p and miR-4497) following IGIV and vitamin supplementation. No changes in microbiome diversity were seen. Conclusion: Elevated CRP is a biomarker for B-cell immunodeficiency and bronchiectasis, with miRs, 122-5p and 4497, as mediators of both IGIV and vitamin supplementation. The robustness of CRP and miRs as biomarkers and their role in PIDD need to be confirmed in larger cohorts. Understanding of aetiology of the disease could help design effective therapies and monitoring methods.

In recent years, the bidirectional communication between the gut microbiome and the brain has emerged as a factor that influences immunity, metabolism, neurodevelopment and behaviour. Cross-talk between the gut and brain begins early in life immediately following the transition from a sterile in utero environment to one that is exposed to a changing and complex microbial milieu over a lifetime. Once established, communication between the gut and brain integrates information from the autonomic and enteric nervous systems, neuroendocrine and neuroimmune signals, and peripheral immune and metabolic signals. Importantly, the composition and functional potential of the gut microbiome undergoes many transitions that parallel dynamic periods of brain development and maturation for which distinct sex differences have been identified. Here, we discuss the sexually dimorphic development, maturation and maintenance of the gut microbiome–brain axis, and the sex differences therein important in disease risk and resilience throughout the lifespan.

Ильясов Р. А., Марсова М. В., Ковтун А. С., Ватлин А. А., Юнес Р. А., Гайфуллина Л. Р., Каскинова М. Д., Николенко А. Г., Квон Х. В., Даниленко В. Н. Микробиом кишечника медоносной пчелы Apis mellifera – потенциальный иточник биологически активных ингредиентов // Современные достижения в области апидологии / Сагитов С. Т. и др. ‒ Уфа: ФГБОУ ВО «БГПУ им. М. Акмуллы», 2021. ‒ C. 23-30. ISBN: 978-5-907475-05-2
Ilyasov R. A., Marsova M. V., Kovtun A. S., Vatlin A. A., Yunes R. A., Gaifullina L. R., Kaskinova M. D., Nikolenko A. G., Kwon H. W., Danilenko V. N. The gut microbiome of the honey bee Apis mellifera – is a potential source of biologically active ingredients // Modern advances in apidology / Sagitov S. T. et al. ‒ Ufa: FSBEI HE "BSPU named after M. Akmulla", 2021. ‒ P. 23-30. ISBN: 978-5-907475-05-2
Аннотация. Микробиом кишечника медоносной пчелы Apis mellifera содержит огра-ниченное количество эволюционно сформировавшихся представителей грамотрицательных (роды Apibacter, Bartonella, Commensalibacter, Gilliamella, Parasaccharibacter, Saccharibacter, Serratia, Snodgrassella, Frischella) и грамположительных бактерий (роды Lactococcus, Lactoba-cillus, Bifidobacterium). Их функции и значимость для отдельной особи и локальной популяции являются в последнее время предметом исследований лабораторий во всем мире. Наш интерес к изучению микробиома кишечника пчелы обусловлен их антимикробным, иммуномодулиру-ющим, нейромодулирующим потенциалом. Лактобактерии и бифидобактерии являются клас-сическими представителями пробиотических бактерий. Их использование в качестве пробио-тиков, парапробиотиков, постбиотиков, ингридиентов в фармокологических препаратах и пер-сонализированных продуктах питания постоянно расширяется. До настоящего времени мик-робиом кишечника медоносной пчелы не использовался в качестве источника пробиотиков. Полный метагеномный анализ микробиома, с использованием алгоритмов поиска заданных генов и их комбинаций, позволяет быстро и эффективно отбирать перспективные штаммы бак-терий. Последующие геномный, транскриптомный, протеомный и метаболомный анализы позволяют отобрать наиболее приемлемые в практическом отношении штаммы. В перспек-тиве, предлагаемая технологическая платформа, отработанная на удобном модельном объекте A. mellifera, позволит использовать ее и на других животных объектах.
Annotation. The gut microbiome of the honey bee Apis mellifera contains a limited number of evolutionarily formed representatives of gram-negative (genera Apibacter, Bartonella, Commen-salibacter, Gilliamella, Parasaccharibacter, Saccharibacter, Serratia, Snodgrassella, Frischella) and gram-positive bacteria (genera Lactococcus, Lactobacillus, Bifidobacterium). Their functions and significance for the individuals and the local population have recently been the subject of research in laboratories around the world. Our interest in the study of the gut microbiome of the honey bees is due to its antimicrobial, immunomodulatory, neuromodulatory potential. Lactobacteria and bifidobacteria are the classic probiotic bacteria. Their use as probiotics, paraprobiotics, postbiotics, pharmaceutical ingredients and personalized food products is constantly expanding. Until now, the honeybee gut microbiome has not been used as a source of probiotics. A complete metagenomic analysis of the microbiome, using algorithms for searching for specified genes and their combina-tions, makes it possible to quickly and efficiently select promising strains of bacteria. Subsequent genomic, transcriptome, proteomic, and metabolomic analyzes make it possible to select the most practically acceptable strains. In the future, the proposed technological platform, tested at a conven-ient model of A. mellifera, allows it to be used on other animals.

As a researcher, author, clinician, and recent (2015) reviewer for PLOS One, I am writing with great concern about the editorial quality and review process of this previously esteemed journal, particularly with regard to the article discussed below. This Letter was sent to the PLOS One Editor by email on 20 July 2017 with receipt acknowledged on 21 July 2017; the response that "We encourage you to contact the corresponding authors of the article directly" is absurd as it will not address either the 1) lack of editorial quality, 2) the defects in the review process, or 3) the [in my opinion] erroneous publication of this article. Oddly, PLOS One does not publish letters and therefore provides no means for the archived biomedical record (e.g., in Pubmed, PubMed Central, Europe PMC, etc) to be corrected; the only public-access option provided by PLOS One is a comments section on their own website which is virtually invisible and unknown to people accessing the article via indexed databases. Thus, given the aforementioned lackluster response and nearly nonexistent channels to correct and critique this PLOS One article, this critique is published online publicly and also noted via Pubmed Commons.

Manganese (Mn) is an often overlooked but important nutrient, required in small amounts for multiple essential functions in the body. A recent study on cows fed genetically modified Roundup®‐Ready feed revealed a severe depletion of serum Mn. Glyphosate, the active ingredient in Roundup®, has also been shown to severely deplete Mn levels in plants. Here, we investigate the impact of Mn on physiology, and its association with gut dysbiosis as well as neuropathologies such as autism, Alzheimer’s disease (AD), depression, anxiety syndrome, Parkinson’s disease (PD), and prion diseases. Glutamate overexpression in the brain in association with autism, AD, and other neurological diseases can be explained by Mn deficiency. Mn superoxide dismutase protects mitochondria from oxidative damage, and mitochondrial dysfunction is a key feature of autism and Alzheimer’s. Chondroitin sulfate synthesis depends on Mn, and its deficiency leads to osteoporosis and osteomalacia. Lactobacillus, depleted in autism, depend critically on Mn for antioxidant protection. Lactobacillus probiotics can treat anxiety, which is a comorbidity of autism and chronic fatigue syndrome. Reduced gut Lactobacillus leads to overgrowth of the pathogen, Salmonella, which is resistant to glyphosate toxicity, and Mn plays a role here as well. Sperm motility depends on Mn, and this may partially explain increased rates of infertility and birth defects. We further reason that, under conditions of adequate Mn in the diet, glyphosate, through its disruption of bile acid homeostasis, ironically promotes toxic accumulation of Mn in the brainstem, leading to conditions such as PD and prion diseases.
Key Words: Autism, cholestasis, glyphosate, manganese, Parkinson’s disease

Dietary fiber (DF) was considered an antinutritional factor due to its adverse effects on feed intake and nutrient digestibility. However, with increasing evidence, scientists have found that DF has enormous impacts on the gastrointestinal tract (GIT) development, digestive physiology, including nutrient digestion, fermentation, and absorption processes of poultry. It may help maintain the small and large intestine’s integrity by strengthening mucosal structure and functions and increasing the population and diversity of commensal bacteria in the GIT. Increasing DF content benefits digestive physiology by stimulating GIT development and enzyme production. And the inclusion of fiber at a moderate level in diets also alters poultry growth performance. It improves gut health by modulating beneficial microbiota in the large intestine and enhancing immune functions. However, determining the source, type, form, and level of DF inclusion is of utmost importance to achieve the above-noted b...

Increased depression, somatization, gut inflammation and wider peripheral inflammation are all associated with the early stages of Parkinson's disease (PD). Classically such concurrent conditions have been viewed as "comorbidities", driven by high levels of stress in a still poorly understood and treated disorder. Here we review the data on how oxidative and nitrosative stress in association with immuno-inflammatory responses, drives alteration in tryptophan catabolites, including kynurenine, kynurenic acid and quinolinic acid that drive not only the 'comorbidities" of PD but also important processes in the etiology and course of PD per se. The induction of indoleamine 2,3-dioxygenase, leading to the driving of tryptophan into neuroregulatory tryptophan catabolite products and away from serotonin and melatonin production, has significant implications for understanding the role of nicotine, melatonin, and caffeine in regulating PD susceptibility. Tryptophan catabolite pathway activation will also regulate blood-brain barrier permeability, glia and mast cell reactivity as well as wider innate and adaptive immune cell responses, all relevant to the course of PD. As such, the "comorbidities" of PD such as depression, somatization and peripheral inflammatory disorders can all be conceptualized as being an intricate part of the biological underpinnings of both the etiology and course of PD. As a consequence, the data reviewed here has treatment implications; relevant to both the course of PD and in the management of L-DOPA induced dyskinesias.

ABSTRACT
Bipolar disorders (BDs) are severe and common psychiatric disorders. BD pathogenesis, clinical manifestations and relapses are associated with numerous circadian rhythm abnormalities. In addition, infradian fluctuations of mood, social activity, weight and sleep patterns are very frequent in BD. Disease course with a seasonal pattern (SP) occurs in approximately 25% of depressive and 15% of manic episodes, which is coupled to a more severe disease symptomatology. The pathophysiological mechanisms of seasonal effects in BD await clarification, with likely important clinical consequences. This review aims at synthesizing available data regarding the underlying pathophysiological mechanisms of seasonality in BD patients, with implications for future research directions in the study of seasonality in BD. Three factors are suggested to play significant roles in BD with SP,
namely the suprachiasmatic nuclei, as well as the melatonergic and photoperiodism systems. It is proposed that BD with SP may be considered as a complex disorder resulting from the interaction
of clock gene vulnerabilities and biological clock neuroplasticity, with environmental factors, such as the response to light. Light seems to play a key role in BD with SP, mainly due to two seasonal
signaling pathways: a light to cortex serotonin transporter pathway, as well as a pathway connecting light to melatonin synthesis. This provides a theoretical framework for BD with SP, including for future research and clinical management. The review proposes that future research should explore markers of seasonality in BD, such as plasma melatonin, sleep–wake rhythms (with actigraphy) and genetic or epigenetic variants within the melatonin synthesis pathway. The role of light in driving BD with SP is an active area of research. Seasonality may also be intimately linked to wider aspects of BD, including via interactions with the gut microbiome, the gut–liver axis, cholesterol regulation,
aspects of metabolic syndrome, vitamin D, decreased longevity, suicide risk and medication treatment targets. Further research on the role of seasonality in BD is likely to clarify the etiology, course and treatment of BD more widely.

The microbiome co-evolved with its human host over a long time and became essential for many processes. Bacteria play a role in maintaining human health as they digest food, produce vitamins and participate in the regulation of metabolism. By influencing the cytokine balance along with the composition and activity of leu-kocytes, they constantly interact with the immune system, affecting innate and adaptive immune homeostasis. A growing number of studies indicate that the microbiome in the human intestine may have an impact on the functions of the central nervous system (CNS), through identified pathways called the gut–brain axis. Recent data show that the human microbiome ecosystem interferes with the brain's development, central signaling systems and behavior. It has been proposed that disruption in the human microbiome may affect the course of psychiatric disorders. The aim of this review is to summarize the recognized pathways of the gut–brain axis that have been thoroughly studied in animal models and to evaluate the role of the dialogue between the mi-crobiota and the central nervous system in schizophrenia, bipolar disorder and depression.

Written for non-experts, this volume introduces the mechanisms that underlie reticulate evolution. Chapters are either accompanied with glossaries that explain new terminology or timelines that position pioneering scholars and their major discoveries in their historical contexts. The contributing authors outline the history and original context of discovery of symbiosis, symbiogenesis, lateral gene transfer, hybridization or divergence with gene flow and infectious heredity. By applying key insights from the areas of molecular (phylo)genetics, microbiology, virology, ecology, systematics, immunology, epidemiology and computational science, they demonstrate how reticulate evolution impacts successful survival, fitness and speciation.
Reticulate evolution brings forth a challenge to the standard Neo-Darwinian framework, which defines life as the outcome of bifurcation and ramification patterns brought forth by the vertical mechanism of natural selection. Reticulate evolution puts forward a pattern in the tree of life that is characterized by horizontal mergings and lineage crossings induced by symbiosis, symbiogenesis, lateral gene transfer, hybridization or divergence with gene flow and infective heredity, making the “tree of life” look more like a “web of life.” On an epistemological level, the various means by which hereditary material can be transferred horizontally challenges our classic notions of units and levels of evolution, fitness, modes of transmission, linearity, communities and biological individuality.
The case studies presented examine topics including the origin of the eukaryotic cell and its organelles through symbiogenesis; the origin of algae through primary and secondary symbiosis and dinoflagellates through tertiary symbiosis; the superorganism and holobiont as units of evolution; how endosymbiosis induces speciation in multicellular life forms; transferrable and non-transferrable plasmids and how they symbiotically interact with their host; the means by which pro- and eukaryotic organisms transfer genes laterally (bacterial transformation, transduction and conjugation as well as transposons and other mobile genetic elements); hybridization and divergence with gene flow in sexually-reproducing individuals; current (human) microbiome and viriome studies that impact our knowledge concerning the evolution of organismal health and acquired immunity; and how symbiosis and symbiogenesis can be modelled in computational evolution.

Contributors
Amanda N. Brothers,  André F. P. Carvalho,  António Manso,  Caetano Souto-Maior,    Douglas Zook,  Élio Sucena,  Francisco Carrapiço,  Francisco Dionisio,  Jennafer A. P. Hamlin,  João Alves Gama,  Laura S. Weyrich,  Luís Correia,    Michael L. Arnold,  Nathalie Gontier,  Noland H. Martin,  Sunni J. Taylor,  Vitor G. Faria,  William C. Summers

More info: https://www.springer.com/us/book/9783319163444#aboutBook

You can read the intro here: https://www.academia.edu/14079107/Reticulate_evolution_everywhere

Le projet de séquençage du Génome humain a fait couler beaucoup
d’encre, mais qu’en est-il d’un projet de décryptage génomique de toute aussi grande envergure, celui du Microbiote humain? Souvent nommé « Seconde réserve de gènes » de l’Homme, les milliers d’espèces de bactéries qui habitent sur ou dans notre corps forment des écosystèmes essentiels et complexes. Nous commençons à peine à percer les
mystères de cet utile mais étrange univers, celui des commensaux de notre espèce avec lesquels nous avons co-évolué. Sans eux, nous ne pourrions digérer tout ce que nous mangeons actuellement, et nous serions démunis devant davantage d’envahisseurs.

Les puissants outils de la Génomique permettent de faire un grand pas vers la connaissance de la diversité et des fonctions de ce microbiote. En identifiant les différentes espèces grâce aux données génétiques, on découvre peu à peu des corrélations entre les types de bactéries présentes et certaines maladies, comme l’obésité, le diabète,
les allergies et la maladie de Crohn. (1)

Ce texte fait un bref survol bibliographique qui permet de comprendre les différences au niveau du microbiote entre les bien-portants et les personnes atteintes de maladies, en particulier l’obésité, et dans quelle mesure ces données ouvrent la porte à de possibles avenues thérapeutiques.

Manganese (Mn) is an often overlooked but important nutrient, required in small amounts for multiple essential functions in the body. A recent study on cows fed genetically modiied Roundup ® -Ready feed revealed a severe depletion of serum Mn. Glyphosate, the active ingredient in Roundup ® , has also been shown to severely deplete Mn levels in plants. Here, we investigate the impact of Mn on physiology, and its association with gut dysbiosis as well as neuropathologies such as autism, Alzheimer's disease (AD), depression, anxiety syndrome, Parkinson's disease (PD), and prion diseases. Glutamate overexpression in the brain in association with autism, AD, and other neurological diseases can be explained by Mn deiciency. Mn superoxide dismutase protects mitochondria from oxidative damage, and mitochondrial dysfunction is a key feature of autism and Alzheimer's. Chondroitin sulfate synthesis depends on Mn, and its deiciency leads to osteoporosis and osteomalacia. Lactobacillus, depleted in autism, depend critically on Mn for antioxidant protection. Lactobacillus probiotics can treat anxiety, which is a comorbidity of autism and chronic fatigue syndrome. Reduced gut Lactobacillus leads to overgrowth of the pathogen, Salmonella, which is resistant to glyphosate toxicity, and Mn plays a role here as well. Sperm motility depends on Mn, and this may partially explain increased rates of infertility and birth defects. We further reason that, under conditions of adequate Mn in the diet, glyphosate, through its disruption of bile acid homeostasis, ironically promotes toxic accumulation of Mn in the brainstem, leading to conditions such as PD and prion diseases.

Through human microbiome sequencing, we can
better understand how host evolutionary and ontogenetic
history is reflected in the microbial function.
However, there has been no information on the gut
metagenome configuration in hunter-gatherer populations,
posing a gap in our knowledge of gut microbiota
(GM)-host mutualism arising from a lifestyle
that describes over 90% of human evolutionary history.
Here, we present the first metagenomic analysis
of GM from Hadza hunter-gatherers of Tanzania,
showing a unique enrichment in metabolic pathways
that aligns with the dietary and environmental factors
characteristic of their foraging lifestyle. We found
that the Hadza GM is adapted for broad-spectrum
carbohydrate metabolism, reflecting the complex
polysaccharides in their diet. Furthermore, the Hadza
GM is equipped for branched-chain amino acid
degradation and aromatic amino acid biosynthesis.
Resistome functionality demonstrates the existence
of antibiotic resistance genes in a population with little
antibiotic exposure, indicating the ubiquitous
presence of environmentally derived resistances.
Our results demonstrate how the functional specificity
of the GM correlates with certain environment
and lifestyle factors and how complexity from the
exogenous environment can be balanced by endogenous
homeostasis. The Hadza gut metagenome
structure allows us to appreciate the co-adaptive
functional role of the GM in complementing the human
physiology, providing a better understanding
of the versatility of human life and subsistence.

Probiotics are live microorganisms which upon ingestion confer health benefits to the host such as prevention of infection in the digestive tract, activate, and modulate the immune response and increase the number of native bacteria in the gut. The present study was aimed to isolate bacteria from donkey dung and characterize for probiotic activity. Bacterial cultures were isolated from excreta of infant donkey and were characterized using standard procedures. Cultures were grown anaerobically, and in total 16 cultures showing Lactobacillus morphology were further screened for the probiotic property. Isolate LB-VII was found to be non-hemolytic and has the ability to tolerate 1.2% bile, pH 1.5~10, 8% NaCl as well as showed growth at 42°C. The culture survived gastric and intestinal environment and showed bile salt hydrolysis activity. LB-VII exhibited 100% auto-aggregation and hydrophobic reaction. The culture could also co-aggregate with Escherichia coli, Enterococcus faecalis, and Staphylococcus aureus, a property, which is required to control pathogens. Moreover, the isolate resist a wide range of antibiotic. All these characters make LB-VII a good probiotic culture and was identified as L. plantarum by molecular methods.

The microbiology of human health and disease has moved forwards significantly in the past decade, with the Human Microbiome Project findings being pivotal. Such is the depth and complexity of the findings that the results continue to be examined. In relation to human skin, the variation in microbial types and how they relate to different ‘ecological niches’ is both fascinating and important for understanding health and disease; the treatment of those diseases; and with human contamination risks. The research is thus important to both clinical and pharmaceutical microbiology.