Normal Flora PDF

Normal Flora DR B REENA RAJKUMARI ASSOCIATE PROFESSOR Normal Flora(Human) A diverse microbial flora is associated with the skin and mucous membranes of every human being from shortly after birth until death. The normal microbial flora inhabiting the human skin, nails, eyes, oropharynx, genita...

Normal Flora DR B REENA RAJKUMARI ASSOCIATE PROFESSOR Normal Flora(Human) A diverse microbial flora is associated with the skin and mucous membranes of every human being from shortly after birth until death. The normal microbial flora inhabiting the human skin, nails, eyes, oropharynx, genitalia, and gastrointestinal tract are harmless in healthy individuals. The normal flora can cause disease in compromised hosts. Viruses and parasites are not considered members of the normal microbial flora in humans by most investigators because they are not commensals and do not aid the host. Gene sequencing helped to identify and classify bacteria based on 16s rRNA and physicochemical properties. From a human health perspective, microbes aid in nutrition, immune system and neurological development, gut maturation, and pathogen defense Dr B Reena Rajkumari / SBST /VIT 2 Normal Flora The human body contains about 1013 cells, routinely harbors about 1014 bacteria.This bacterial population constitutes the normal microbial flora. The normal microbial flora is relatively stable, with specific genera populating various body regions during particular periods in an individual's life. Microorganisms of the normal flora may aid the host (by competing for microenvironments more effectively than pathogens or by producing nutrients the host can use), may harm the host (by causing dental caries, abscesses, or other infectious diseases), or may exist as commensals (inhabiting the host for long periods without causing detectable harm or benefit). Dr B Reena Rajkumari / SBST /VIT 3 Normal Flora The normal flora in humans usually develops in an orderly sequence, or succession, after birth, leading to the stable populations of bacteria that make up the normal adult flora. The main factor determining the composition of the normal flora in a body region is the nature of the local environment, which is determined by pH, temperature, redox potential, and oxygen, water, and nutrient levels. Other factors such as peristalsis, saliva, lysozyme secretion, and secretion of immunoglobulins also play roles in flora control. The local environment is like a concerto in which one principal instrument usually dominates. For example, an infant begins to contact organisms as it moves through the birth canal. A Gram-positive population (bifidobacteria arid lactobacilli) predominates in the gastrointestinal tract early in life if the infant is breast-fed. Breast milk has unique microbiota, including beneficial, symbiotic, and potential probiotics In the breastfed infants, breast milk contains unique human milk oligosaccharides (HMOs), which contain large amounts of complex oligosaccharides that modulate the intestinal microbiota and acting as prebiotics for the enrichment of the beneficial bacteria This bacterial population is reduced and displaced somewhat by a Gram-negative flora (Enterobacteriaceae) when the baby is bottle-fed. The type of liquid diet provided to the infant is the principal instrument of this flora control Dr B Reena Rajkumari / SBST /VIT 4  Bovine milk is a significant substitute for human breast milk and holds great importance in infant nutrition and health. Apart from essential nutrients, bovine milk also contains bioactive compounds, including a microbiota derived from milk itself rather than external sources of contamination Bovine milk microbiota supports early-life gut development by improving the intestinal microbiota and immune functions. Dr B Reena Rajkumari / SBST /VIT 5  Various microflora in rumen of cow The polysaccharic plant fibrils are degraded by cellulolytic bacteria, and the substrate formed is acted upon by other bacteria. The overall energy production as well as digestion is decided by the intactness of the resident communal flora. Disturbances in the homogeneity gastrointestinal microflora has severe effects on the digestive system and various other organs. This disharmony in communal relationship also causes various metabolic disorders. The dominance of methanogens sometimes lead to bloating, and high sugar feed culminates in ruminal acidosis. Dr B Reena Rajkumari / SBST /VIT 6  The intestinal microbiota of infants plays an important role in early life and affects health throughout lifespan. The mother is closely associated with the infant microbiota, by helping to establish it through her own gut microbiota, intrauterine and birth canal environments, and feeding. Dr B Reena Rajkumari / SBST /VIT 7  Development of infant intestinal microbiota during the first 1000 days of life. The use of antibiotics during pregnancy or childbirth may increase the relative abundance of Firmicutes and decrease that of Lactobacillus or Bifidobacterium Studies have shown that supplementing Lactobacillus GG (LGG) (1.8 × 1010 CFU/d) from 36 weeks of pregnancy till delivery can promote the colonisation of Bifidobacteria in the intestines of breastfed infants Mothers with higher stress levels had babies with a higher prevalence of pathogenic bacteria, such as Escherichia coli and Salmonella, and a lower prevalence of beneficial bacteria, such as Lactobacillus and Bifidobacterium. Dr B Reena Rajkumari / SBST /VIT 8 Characteristics and influencing factors of female intestinal microbiota during pregnancy. Dr B Reena Rajkumari / SBST /VIT 9  Human microbiome development and transmission. Panel (A) Representation of humans’ first contact with microbes during birth and a comparison of how delivery mode (vaginal delivery and C-section) impacts infant microbiota. Panel (B) Human microbial transmission and development from pre-birth to adulthood. Microbes that colonize newborns will form a variety of niches in different body sites, adult diversity is attained at ∼3 years old. Elder people have a decrease in microbial diversity leading to dysbiosis that may be associated with neurodegenerative disorders. Panel (C) Practices of breastfeeding and/or formula feeding play an important role in shaping the intestinal microbiome. Formula feeding is associated with intestinal inflammation, with an increase in Enterobacteriaceae and Clostridium spp. and reduced levels of probiotic Bifidobacterium and Lactobacillus spp. acquired via lactation Dr B Reena Rajkumari / SBST /VIT 10 Normal delivery and C -sections studies have shown that intestinal microbiota composition in vaginally delivered infants differs from that of infants delivered by caesarean section Infants delivered vaginally obtain microorganisms from the birth canal of the mother, most of which are anaerobic bacteria. These microorganisms constitute the initial infant microbiota, with the most significant enrichment of Bacteroides The vagina of pregnant women contains a large amount of Lactobacillus, that keep its pH low, inhibiting the growth of harmful bacteria, and preventing harmful bacteria from entering the uterus to infect the amniotic membrane, placenta, or foetus Microbiota of naturally delivered babies was similar to the vagina microbiota of the mother. During the natural delivery process, the mother passed vaginal microorganisms to the baby vertically, wherein.Lactobacillus was the main genus. In addition, a high abundance of Bifidobacteria, Bacteroides, Prevotella, and Leptothrix Dr B Reena Rajkumari / SBST /VIT 11  Normal delivery and C -sections Compared with natural childbirth, infants delivered by caesarean section lose the only opportunity to come into contact with the vaginal microbiota of the mother. Their first contact is with the surrounding environment and the skin of the mother. As a result, conditional pathogens from the hospital environment have been found in their intestines, including Enterococcus, Enterobacter, and Klebsiella The composition of early intestinal microbiota in infants born by caesarean section is similar to that of the skin of the mother, mainly containing facultative anaerobes, such as Staphylococcus, Propionibacterium, Corynebacterium, low-abundance Bacteroides, and Bifidobacteria. In addition, intestinal colonisation by Bacteroides in infants delivered by caesarean section is delayed for up to 1 year, and the diversity of intestinal microbiota is low Dr B Reena Rajkumari / SBST /VIT 12 Early-life respiratory tract and the gut microbiome. The early-life microbiome plays an important role in the infant’s overall health. Several factors can affect the early-life microbiome establishment and colonization. The perturbations of the infant microbiome can impact the long-term microbiota composition, potentially determining the predisposition to inflammatory diseases, such as severe RSV disease. Dr B Reena Rajkumari / SBST /VIT 13 Normal Flora Various body sites of vertebrates provide stable and nutrient-rich ecosystems for a diverse range of commensal, opportunistic, and pathogenic microorganisms to thrive. The collective genomes of these microbial symbionts (the microbiome) provide host animals with several advantages, including Metabolism of indigestible carbohydrates, Biosynthesis of vitamins, and Modulation of innate and adaptive immune systems Factors that impact microbial composition and function in the host are pH, temperature, the host species, age and geographic location in addition the diet and dietary interventions also influence microbial composition. Dr B Reena Rajkumari / SBST /VIT 14  Age-related changes in the human gut microbial eco system, and potential factors that could affect microbiota composition at different stages of life.- diversity: species (taxa) richness within a single host / microbial environment;-diversity: diversity in microbial community (taxonomic abundance profiles) between different environments / samples) Gut dysbiosis in the elderly increases risk of aging-associated diseases. The composition of the gut microbiota changes with age, causing a mild inflammation in the elderly. This change can be exacerbated by additional intrinsic and extrinsic factors, such as uptake of antibiotics and diet. Frail elderly people show increased gut dysbiosis, a severe decrease of beneficial commensal bacteria, such as Akkermansia muciniphila Dr and SCFA-producing B Reena bacteria, Rajkumari / SBST /VIT and a marked increase of opportunistic and 15 potentially proinflammatory commensal microbes. Dr B Reena Rajkumari / SBST /VIT 16 Dr B Reena Rajkumari / SBST /VIT 17 Normal Flora ( Plants and Fish) Plant phyllosphere has been found to be dominated by strict aerobes, represented by Methylobacteriaceae and Sphingomonadaceae (Alpha proteobacteria),but their abundance is low in the plant root, being replaced by a large diversity of facultative anaerobes Microbiota of plants and fish have several groups of facultative anaerobes in common. Multiple apertures of fish, i.e., skin, gills, and gut, are constantly in contact with ambient water, each of which is covered with thick mucus biofilm, which bears resemblance to the plant root system. Comamonadaceae and Oxalobacteraceae (Betaproteobacteria) as well as Flavobacteriaceae (Bacteroidetes), which dominate the leaf-to-root microbiota of plants, are also abundant in fish mucus, especially in gill microbiota Bacteria known as plant growth-promoting microbes (PGPM) such as Pseudomonadaceae (Gamma proteobacteria) and Rhizobiales (Alpha proteobacteria) are also frequent colonizers in fish intestinal microbiota Dr B Reena Rajkumari / SBST /VIT 18 Microbiome analysis methods The development of HTS and analysis methods has provided new insights into the structures and functions of microbiome Dr B Reena Rajkumari / SBST /VIT 19 Dr B Reena Rajkumari / SBST /VIT 20 Dr B Reena Rajkumari / SBST /VIT 21 Advantages and limitations of high-throughput method (HTS methods) used in microbiome research. A Introduction to HTS methods for different levels of analysis. At the molecule-level, microbiome studies are divided into three types: microbe, DNA, and mRNA. The corresponding research techniques include culturome, amplicon, metagenome, metavirome, and metatranscriptome analyses. B The advantages and limitations of various HTS methods for microbiome analysis Dr B Reena Rajkumari / SBST /VIT 22 Dr B Reena Rajkumari / SBST /VIT 23 Dr B Reena Rajkumari / SBST /VIT 24 Germ Free Mice Models- Gnotobiology Gnotobiology has revolutionized the study of microbiota-host interactions The development of germ-free (GF) mice, which lack all micro-organisms, effectively allowing the transfer of selective bacterial species or whole fecal microbiota The pioneers of gnotobiology were Nuttall and Thierfelder, who have rederived the first germ-free animals. Germ-free mice can be utilized to unravel the functionality of individual murine or human bacterial species, microbial consortia, or human fecal transplants in health and disease, under highly defined conditions. Thereby, gnotobiology can reveal crucial genetic, microbial, and environmental determinants underlying host-microbiota interactions. GF models, on the other hand, serve as a completely blank microbial background to offer an invaluable opportunity to see not only correlative relationships but also causal effects through the association of gut microbes with the host Dr B Reena Rajkumari / SBST /VIT 25 Gnotobiotic mouse model with a synthetic human gut microbiome Dr B Reena Rajkumari / SBST /VIT 26 Germ Free Mice Models- Gnotobiology The capabilities of GF mice have further been demonstrated through fecal microbiota transplantation (FMT), in which fecal samples of donors are transplanted into the guts of recipients. FMT was first proposed in 1958, and the concept was strengthened in 1983 with the treatment of Clostridium difficile-induced pseudomembranous enterocolitis using the transfer of fecal enema, thus highlighting the ability of the transplanted microbiota to modulate host physiology and even alleviate disease Dr B Reena Rajkumari / SBST /VIT 27 Dr B Reena Rajkumari / SBST /VIT 28 Holo-genomics Hologenomics, the integrated study of the genetic features of a eukaryotic host alongside that of its associated microbes, is becoming a feasible — yet still underexploited — approach that overcomes this limitation The term “holobiont” (Margulis and Fester, 1991) refers to a host and all its associated microbes, and the term “hologenome” refers to the genomes of the host and the microbes. Some scientists consider the holobiont as the unit upon which natural selection acts, whereas others have criticized this metaphor, and question whether the microbiome can respond to natural selection, given its limited heritability microorganisms play in animal health and development. Animals provide a diverse array of habitats for microorganisms to colonise, with virtually all animals harboring multiple types of microbial taxa. These include bacteria, viruses, archaea and eukaryotic microbes such as fungi and protozoa, which form dynamic communities that interact with host species (McFall-Ngai et al., 2013; Colston and Jackson, 2016). This diversity of microorganisms and their genes, collectively termed the microbiome, plays key functional roles on and within the host body (Mueller and Sachs, 2015). Since the discovery of these complex relationships, the host and its associated microbiome are now often considered as a metaorganism (holobiont) (Bosch and McFall-Ngai, 2011). Hologenomics is the omics study of hologenomes. A hologenome is the whole set of genomes of a holobiont, an organism together with all co-habitating microbes, other life forms, and viruses. The term hologenome originated from the hologenome theory of evolution, which postulates that natural selection occurs on the holobiont level, hologenomics uses an integrative framework to investigate interactions between the host and its associated species. Examples include gut microbe or viral genomes linked to human or animal genomes for host-microbe interaction research. Hologenomics approaches have also been used to explain genetic diversity in the microbial communities of marine sponges. Dr B Reena Rajkumari / SBST /VIT 29 Dr B Reena Rajkumari / SBST /VIT 30 Dr B Reena Rajkumari / SBST /VIT 31 Normal Flora in Health , disease pathogenesis Dr B Reena Rajkumari / SBST /VIT 33 Normal Flora in health and disease Dr B Reena Rajkumari / SBST /VIT 34 Dr B Reena Rajkumari / SBST /VIT 35 Mechanisms by which the normal flora competes with invading pathogens Dr B Reena Rajkumari / SBST /VIT 37 Dr B Reena Rajkumari / SBST /VIT 38 Dr B Reena Rajkumari / SBST /VIT 39  Lewy bodies are clumps of proteins that build up inside certain neurons (brain cells). Dr B Reena Rajkumari / SBST /VIT 40  Animal studies have demonstrated that changes in the gut microbiota result in altered host function, in domains relevant to IBS (gut motility, visceral pain responses, intestinal permeability, and brain function and behaviour) Gut microbiota composition is altered in at least a subset of patients with IBS (most commonly diarrhoea-predominant IBS), but no microbial 'signature' that could act as an IBS biomarker has been identified Considerable interest exists in the ability of bacteria to produce substances that interact with the host to influence gut and brain function, which include fatty acids, tryptophan and neurotransmitters Dysbiosis in IBS is characterized by a loss of microbial diversity and temporal instability; contributing factors include diet, stress, infection, antibiotic usage, immune activation and low-grade inflammation The gut microbiota from patients with IBS, but not healthy individuals, can induce gut dysfunction in mice reminiscent of that seen in IBS, strongly suggesting that the microbiota contributes to the expression of IBS Emerging evidence supports the efficacy of select and limited microbiota-directed therapies in treating IBS, and to date these include prebiotics, probiotics and selected antibiotics Dr B Reena Rajkumari / SBST /VIT 41 Causes for Dysbiosis Environmental pollution Environmental pollution is closely related to body health. Recently, the effect of heavy metals, atmospheric particulate matter, micro plastics, pesticides, disrupting chemicals or xenobiotics and other pollutants on composition and function of microbiota and thereby inducing dysbiosis have been widely reported Nutrition diet The effect of diet on gut microbiota via nutritional status has two sides. On one hand, undernutrition may relate to abnormal gut microbial population, which can perpetuate the vicious cycle of pathophysiology. On the other hand, overnutrition lead to obesity have adverse effect on the gut microbiota Poor diets such as long-term high-fat diet (HFD), high-salt diet (HSD) and high-fat and high-sugar diet (HSFD) can significantly change the composition of gut microbiota and lead to varying degrees of dysbiosis. The appearance of dysbiosis is accompanied by changes in metabolites such as lipopolysaccharide (LPS), bile acids and serotonin were associated with metabolism- related diseases such as obesity and diabetes HFD can affect the composition and metabolism of gut microbiota and induce intestinal inflammation. The unfavorable metabolites produced during fermentation process such as trimethylamine oxide and hydrogenDrsulfide may be one of the triggers for dysbiosis B Reena Rajkumari / SBST /VIT 42 Causes for Dysbiosis Drugs The effect of drugs on intestinal microecology is bidirectional. On the one hand, drugs can inhibit the growth and regulation of pathogenic bacteria; on the other hand, drugs can disturb the normal flora structure and cause gut microbiota dysbiosis Antibiotics, which are widely used as antimicrobial agents, are shown to kill or inhibit sensitive flora in large quantities, simultaneously can cause intestinal barrier damage, and induce intestinal inflammatory substances Bacterial diversity and richness were decreased with the combination of clindamycin and metronidazole. At the phylum level, the abundance of Firmicutes, Bacteroidetes, and Proteobacteria were altered The level of Proteobacteria and Bacteroidetes was decreased and the number of Firmicutes was increased after treatment with ceftriaxone Under lincomycin treatment, the number of Proteobacteria and Firmicutes were increased, but the Bacteroidetes were decreased, and the infiltration of inflammatory cells was found by histopathological observation of ileum Age, lifestyle, individual physiological characteristics, and many other reasons can also lead to dysbiosis of gut microbiota Dr B Reena Rajkumari / SBST /VIT 43 Dr B Reena Rajkumari / SBST /VIT 44  The impact of dietary patterns on gut microbiota and intestinal health. A schematic overview depicting the importance of diet and dietary constituents in discriminating between a healthy (A) or an unhealthy (B) state of the gut barrier function by modulating the composition and functionality of the gut microbiota Dr B Reena Rajkumari / SBST /VIT 45  There is growing evidence that prebiotics can effectively alleviate gut microbiota dysbiosis A prebiotic need to meet three standards: (1) it’s not absorbed in the upper digestive tract; (2) it can promote the growth of beneficial bacteria; (3) its metabolites are beneficial to human health Sargassum fusiforme, a perennial warm-temperature algae Polysaccharides from Sargassum fusiforme in vitro fermentation for 24 h, the utilization of carbohydrate was 53.17 %, and the contents of total SCFAs increased by 10.77 times. The diversity of gut microbiota was altered by a significant decrease in pH due to acid production. Compared with the control group, the number of beneficial bacteria including Bifidobacterium, Ruminococcaceae_UCG-014 and Lactobacillus were significantly increased in the polysaccharide group Gracilaria, also known as irish moss or ogonori, is a genus of red algae. Sulfated polysaccharides from Gracilaria Lemaneiformis were rarely degraded during digestion and 53.7 % of which were utilized by gut microbiota to produce large amounts of SCFAs during fermentation In vitro fermentation model, oyster polysaccharides promoted SCFAs production and up-regulated the abundance of beneficial bacteria such as Bacteroides and Prevotella MPs can alter the richness and diversity of gut microbiota and play a prebiotics role by increasing the abundance of probiotics and related functional bacteria Dr B Reena Rajkumari / SBST /VIT 46 Dr B Reena Rajkumari / SBST /VIT 47  Gut microbiota and SCFA Gut microbiota encompasses a wide variety of commensal microorganisms consisting of trillions of bacteria, fungi, and viruses. This microbial population coexists in symbiosis with the host, and related metabolites have profound effects on human health. In this respect, gut microbiota plays a pivotal role in the regulation of metabolic, endocrine, and immune functions. Bacterial metabolites include the short chain fatty acids (SCFAs) acetate (C2), propionate (C3), and butyrate (C4), which are the most abundant SCFAs in the human body and the most abundant anions in the colon. SCFAs are made from fermentation of dietary fiber and resistant starch in the gut. They modulate several metabolic pathways and are involved in obesity, insulin resistance, and type 2 diabetes Dr B Reena Rajkumari / SBST /VIT 48  The gut-brain is a bidirectional link between the central nervous system (CNS) and the enteric nervous system (ENS), which communicates between four information carriers in the so-called gut connectome: 1) the vagal and spinal afferent neurons, 2) immune messages carried by cytokines, 3) endocrine messages carried by gut hormones and 4) microbial factors that reach the brain through the bloodstream Dr B Reena Rajkumari / SBST /VIT 49 Short-chain fatty acids (SCFAs) Gut microbiota ferment indigestible dietary fiber to generate SCFAs, mainly acetate, propionate and butyrate. Due to their anti-inflammatory properties, short-chain fatty acids may have a wide range of beneficial effects on your body including chronic diseases like neurodegenerative conditions, obesity, diabetes, immunological conditions, and intestinal disorders Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota–gut–brain crosstalk Short-chain fatty acids (SCFAs) are speculated to have a mediational role in the microbiota–gut–brain axis crosstalk. SCFAs might influence psychological functioning via interactions with G protein-coupled receptors or histone deacetylases and exert their effects on the brain via direct humoral effects, indirect hormonal and immune pathways and neural routes. Dietary intervention studies indirectly implicate a mediational role for SCFAs in cognition and emotion. Animal studies provide direct evidence of the effects of SCFAs on neuropsychiatric disorders and psychological functioning, whereas human studies are sparse, suffer from methodological limitations and offer inconsistent conclusions. SCFAs should be quantified in the systemic circulation in dietary intervention studies, in which the effects on psychological functioning and psychopathology are an outcome of interest. SCFAs could ultimately be used as interventional substances to target microbiota–gut–brain interactions in humans Dr B Reena Rajkumari / SBST /VIT 50  Biosynthesis of SCFAs via carbohydrate fermentation and bacterial cross-feeding. Bacterial conversion of dietary Fiber in the gut à synthesis of acetate, butyrate, and propionate. Acetate from pyruvate via acetyl- CoA and also via the Wood- Ljungdahl pathway. Butyrate is produced from 2 molecules of acetyl-CoA, yielding aceto-acetyl- CoA, which is converted to butyryl- CoA via β-hydroxybutyryl-CoA and crotonyl-CoA. Propionate can be formed from phosphoenolpyruvate through the succinate pathway or the acrylate pathway, in which lactate is reduced to propionate. Gut microbes can also produce propionate through the propanediol pathway from fucose and rhamnose Dr B Reena Rajkumari / SBST /VIT 51  Pathways involved in the biosynthesis of SCFAs from dietary fiber and carbohydrate fermentation by the colonic microbiota. The three major SCFAs are: (1) acetate which originates via the Wood–Ljungdahl pathway or acetyl-CoA; (2) butyrate synthesized from two molecules of acetyl- CoA; (3) propionate from PEP involving the acrylate pathway or the succinate pathway or the propanediol pathway after microbial transformation of fucose and rhamnose. Dr B Reena Rajkumari / SBST /VIT 52 The intestinal effects of SCFAs The intestinal effects of SCFAs are related to tighter (less leaky) epithelium, thereby inhibiting leakage of bacterial products like lipopolysaccharides (LPS). Tight-junction proteins (such as occludins, claudins, and junctional adhesion molecules) affect gut permeability. Butyrate may have a protective effect on the epithelial barrier by increasing claudin-1 and maintaining the integrity of the gut barrier through the redistribution of occludin and zonula occludens-1 (ZO-1). Butyrate can also influence mucus production by stimulating special cells named Goblet cells in the intestinal mucosa, protecting against foreign and harmful substances (Blaak et al. Benef Microbes 2020). Intestinal epithelium may also respond to SCFAs be enhancing release of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), thereby reducing satiety and increasing pancreatic insulin release. Propionate can be converted to glucose via intestinal gluconeogenesis (IGN) promoting satiety and reduced hepatic glucose formation. Dr B Reena Rajkumari / SBST /VIT 53 Immunological effects of SCFAs Many types of immune cells like macrophages, neutrophils, regulatory T cells, CD4+ and CD8+ T cells, dendritic cells, and innate lymphoid cells (ILCs), seem to be beneficially influenced by SCFAs, mostly via G protein-coupled receptors like GPR41 and GPR43. Butyrate is a potent inducer of the expression of the anti-microbial protein cathelicidin (Schauber et al. Immunology 2006). SCFAs in the gut lumen are transported across the epithelial barrier into the bloodstream and to other organs like the pancreas, where SCFAs may regulate insulin secretion. Dietary fermentable fibers changed the microbiota of the murine gut and lung, particularly by altering the ratio of Firmicutes to Bacteroidetes. Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic lung inflammation, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease (Trompette et al. Nat Med 2014). Supplementation of mice with propionate altered bone marrow hematopoiesis by generation of macrophage and dendritic cell precursors Dr B Reena Rajkumari / SBST /VIT 54  Luminal acetate and propionate sensed by GPR41/43 release peptide YY (PYY) and glucagon- like peptide-1 (GLP-1), affect satiety and intestinal transit. Propionate can be converted to glucose by intestinal gluconeogenesis (IGN) and promote satiety and reduced hepatic glucose formation. Luminal butyrate is anti- inflammatory via GPR109A and inhibits histone deacetylases. SCFAs can act on the enteric nervous system (ENS) by stimulating motility or immune cells sensed by GPR41/43 and reduce inflammation. Blood SCFA can activate G-coupled Rs in the lungs, pancreas, adipose tissue, bone marrow, brain, liver, and muscles Dr B Reena Rajkumari / SBST /VIT 55 Effects on the nervous system by SCFA SCFAs may affect the brain by regulating expression of the gene encoding tryptophan hydroxylase, a key enzyme of the serotonin biosynthesis. SCFAs also promote formation of neurons and microglia, improve memory, reduce nerve inflammation, and enhance blood-brain barrier (Silva et al. Front Endocrinol 2020). The central nervous system and enteric nervous system communicate via vagal and autonomic pathways to modulate brain function as well as gastrointestinal functions like satiety. SCFAs affect mood and cognitive processes via alteration of blood concentrations of tryptophan, precursor for the signaling molecule 5- hydroxytryptamine (5-HT) (Silva et al. Front Endocrinol 2020; Soty et al. Cell Metabol 2017). Dr B Reena Rajkumari / SBST /VIT 56 SCFA as an energy source SCFAs are probably the most important energy sources for colonocytes (epithelial cells in colon) and may provide up to 8 % of daily energy (Bergman Physiol Rev 1990) with butyrate contributing the most (Blaak et al. Benef Microbes 2020). Some studies suggest that SCFAs may reduce lipolysis (mobilization of fatty acids) as well as insulin-mediated fat accumulation in adipose tissue and reduce accumulation of hepatic and skeletal muscle lipids (Bongiovanni et al. Int J Sports Med 2021). These effects may be beneficial for optimal body weight and perhaps type 2 diabetes. However, the extra 8 % of energy provided by SCFA absorption may represent surplus energy and thereby promote enhanced body weight (Silva et al. Front Endocrinol 2020). Dr B Reena Rajkumari / SBST /VIT 57 Biomarkers for gut microbiota and human health SCFA may be used as biomarkers of a healthy gut because high levels might indicate many beneficial factors related to health. Fecal SCFAs are good biomarkers of the gut microbiota ecosystem and dynamics of SCFAs in the human body (Yamamura et al. Biosci Microbiota Food Health 2021). Two studies on the relation between serum SCFAs and multiple sclerosis (MS) have been recently published. Trend et al. (Sci Rep 2021) showed that serum propionate levels of CIS (clinically isolated syndrome)/MS patients, were significantly lower than among healthy controls. Several CIS/MS patients also had butyrate and acetate levels below levels from healthy controls. Olsson et al. (Front Immunol 2021) observed that serum acetate levels were lower in MS patients than in controls. Dr B Reena Rajkumari / SBST /VIT 58 Dr B Reena Rajkumari / SBST /VIT 59 Dr B Reena Rajkumari / SBST /VIT 60 Probiotics, Prebiotics and Microbiome Synbiotics are products that have both probiotic and prebiotic components (Anand et al., 2019). An example is the use of Lactobacillus and Bifidobacterium along with carbohydrates (Rigo-Adrover et al., 2018). A recent study found beneficial effects in cream cheese containing Lactococcus chungangensis. Specifically, it was found that rats that were administered cream cheese containing this microorganism presented lower IgE levels, increased fecal Bacteroides, Lactobacillus and Ruminococcus, as well as increased SCFA production (Kim et al., 2019b). A study with fermented milk containing probiotic Bifidobacterium breve and prebiotic galactooligosaccharides found that people who were administered this milk had increased hydration and defecation as well as more clear skin (Mori et al., 2016); suggesting the potential beneficial effects on skin and gut health that a combination of probiotics and prebiotics can have, i.e., synbiotics Kimchi is a group of fermented and salted vegetables that include cabbage, carrot, pear, apple, and ingredients such as chili, pepper, soybean, and ginger (Patra et al., 2016). Kimchi is usually a fermented food that has high concentrations of Leuconostoc, but can also have good concentrations of Lactobacillus, Weissella, and Pseudomonas (Jeong et al., 2013). Apart from bacteria, Kimchi has also been found to contain archaea and yeast (Chang et al., 2008). A study found that Lactobacillus Plantarum, which is usually found on Kimchi, can reduce mesenteric adipose tissue and increase the genomic expression of lipid oxidation genes (Park et al., 2017), features that suggest Kimchi may contribute to weight loss. Dr B Reena Rajkumari / SBST /VIT 61 Probiotics, Prebiotics and Microbiome In China, Kombucha is a popular fermented tea beverage that is produced through aerobic fermentation and uses both bacteria and yeast (Gaggìa et al., 2018). Acetic acid and lactic acid-producing species such as Acetobacter and Lactobacillus, as well as yeasts such as Saccharomyces are the most commonly found organisms in Kombucha (Coton et al., 2017). The acid produced by these bacteria lower the pH of Kombucha, making it difficult for pathogenic bacteria such as E. coli to grow inside the beverage (Gaggìa et al., 2018). Although only recently Kombucha has been associated with benefits in health and the microbiota, a recent study found that administration of Kombucha tea reduces fat accumulation in the liver of rats with non-alcoholic fatty liver disease and decreases specific bacteria such as Clostridium in a mouse model (Jung et al., 2019). A study found that Gluconobacter, a bacteria commonly found in Kombucha, can produce D- Saccharic acid-1,4-lactone - a compound that has been this compound has been found to inhibit oxidative stress and the release of pro-inflammatory cytokines (Bhattacharya et al., 2013). Dr B Reena Rajkumari / SBST /VIT 62 Faecal matter transplants (FMT)-microbial seeding The target of the vaginal seeding is to partially restore the microbiome of a baby born via C- section, using the vaginal microbiota of the mother upon delivery (Dominguez-Bello et al., 2016). The purpose is to transfer the vaginal flora from mothers to the mouth, nose, and skin of the newborn. Restoration of the neonatal microbiota born via C-section with maternal vaginal microbes has raised concerns about infection risks (Dominguez-Bello et al., 2019). Not all mothers qualify as candidates to be donors of vaginal fluids for the seeding procedure. Only women who were not carriers of infectious diseases nor tested positive for Sexually Transmitted Diseases (STDs) at the time of delivery were allowed to donate (Dominguez-Bello et al., 2016). Also, oral-fecal transplantation has proven successful in changing the neonate microbiota. De Vos and colleagues theorized that vaginally born babies might get their microbes from accidentally ingesting their mother’s stool during the birthing process (Helve et al., 2021). They diluted fecal matter into breast milk donated from the bank and pumped from the mothers themselves—and then fed it to their babies. The gut microbiome of the babies later resembled those born vaginally (Helve et al., 2021). Dr B Reena Rajkumari / SBST /VIT 63 Microbial seeding - Faecal matter transplants (FMT) Microbial communities can also be restored by microbial seeding and fecal matter transplants (FMT). Even though microbial dysbiosis is expected as aging occurs and depends on environmental and birth-related factors, several restoration techniques have been developed to regulate microbial communities and improve health. So far, the best examples of microbiome restoration are vaginal and fecal microbial transfer to neonates (seeding) and fecal microbiota transplantations. The vaginal microbial transfer has been recently reported as the technique of acquiring vaginal bacterial communities from a mother awaiting a C-section and smearing the baby after birth (Dominguez-Bello et al., 2016). oral-fecal transplantation has proven successful in changing the neonate microbiota. De Vos and colleagues theorized that vaginally born babies might get their microbes from accidentally ingesting their mother’s stool during the birthing process (Helve et al., 2021). They diluted fecal matter into breast milk donated from the bank and pumped from the mothers themselves—and then fed it to their babies. The gut microbiome of the babies later resembled those born vaginally Dr B Reena Rajkumari / SBST /VIT 64 Microbial seeding - Faecal matter transplants (FMT)- FMT is the administration of fecal matter from a healthy adult donor into the intestinal tract of an affected adult to change and restore their microbiome to healthy conditions (Pigneur and Sokol, 2016). In recent studies, it has been recognized that FMT is extremely efficient in treating inflammatory bowel disease (Tanaka and Nakayama, 2017), psoriasis (Yin et al., 2019), Crohn’s Disease (Sarrabayrouse et al., 2020), Clostridium difficile infections (Cammarota et al., 2017), and ulcerative colitis (Lleal et al., 2019). FMT has been known to suppress intestinal apoptosis, which reduces inflammatory responses, regulates lymphocytes, and alters the microbiota (Burrello et al., 2019). It has been shown that fecal matter from a healthy donor has the capacity to overturn dysbiosis by restoring alpha-diversity and increasing the abundance of health-related microbiota (Lleal et al., 2019). The long-lasting effects of FMT have been reported in patients with Irritable Bowel Syndrome (IBS) (El-Salhy et al., 2022). Dr B Reena Rajkumari / SBST /VIT 65 Dr B Reena Rajkumari / SBST /VIT 66 A shift in the understanding of the microbial-host coevolution from the “separation” theories to the holistic approach. The hosts and their associated microbiota are assumed to have coevolved with each other, whereby different approaches are considered to describe the coevolution theory. According to the “separation” approach (upper part of the figure), the microorganisms can be divided into pathogens, neutral, and symbionts, depending on their interaction with their host. The coevolution between host and its associated microbiota may be accordingly described as antagonistic (based on negative interactions) or mutualistic (based on positive interactions). The recent emerge in publications about opportunistic pathogens and pathobionts gave a shift towards holistic approach in the coevolutions theory (lower part of the figure). The holistic approach sees the host and its associated microbiota as one unit (so-called holobiont), that coevolves as one entity. According to the holistic approach, holobiont’s disease state is linked to dysbiosis, low diversity of the associated microbiota, and their variability: a so-called “pathobiome” state. The healthy state, on the other hand, is accompanied with eubiosis, high diversity, and uniformity of the respective microbiota. The dynamic flow of microorganisms from one host to another and to the environment, described by the One Health concept, underpins the holistic approach in the coevolution Dr B Reena Rajkumari / SBST /VIT 67 Dr B Reena Rajkumari / SBST /VIT 68