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Bioactivities of postbiotics

Over 10 trillion microbial cells in the human GI produce specific metabolites and bioactive compounds that trigger the host’s immunological and metabolic pathways. Microbial symbiosis and stable human-intestinal microbiota communities that promote health and are resistant to disruption require this homeostatic symbiosis between the host and the microbiota. Postbiotics, a novel biotic, are inanimate microbes and their components that benefit the host. Microbial activity produces postbiotics, which benefit the host’s gut health. During lysis, bacteria release enzymes, peptides, teichoic acids, peptidoglycan-derived muropeptides, polysaccharides, cell surface proteins, and organic acids.

Postbiotics are bioactive compounds created after fermentation in the matrix that can alleviate food allergies and enhance immunological tolerance, especially in young children and infants. Structure, elemental makeup, proteins, vitamins, lipids, organic acids, and complex compounds are used to categorize them. Postbiotics have immunological effects that boost mucin formation and promote claudin synthesis. They show promise for the early detection and effective management of digestive disorders in children. The optimal parent cell strains, doses, and reasonably priced postbiotics will require further study. High pressure, ultraviolet light, formalin inactivation, thermal treatments, ionizing radiation, and sonication can increase food nutrition, shelf life, and health.

The Impacts of Postbiotics in Human Health

Postbiotics are immunomodulatory, antihypertensive, anti-inflammatory, antiproliferative, hypocholesterolemia, anti-obesogenic, and antioxidant. Probiotics like teichoic acid, indole, lipopolysaccharide, muramyl dipeptide, and lactospin make them. They boost intestinal health-promoting Lactobacillus and Bifidobacterium bacteria. Postbiotics lower blood sugar and improve insulin function in obese persons. They have anti-inflammatory, anti-hypertensive, immunomodulation, hypocholesterolemia, anti-proliferative, anti-obesogenic, and antioxidant properties. Postbiotic advantages depend on the microbe or bacteria utilized.

 Postbiotics get preference over probiotics

Postbiotics improve gut microbiota health and have antibacterial, immune-modulating, and anti-inflammatory properties. They last less than probiotics and are easier to travel, store, and maintain. Postbiotics are safer, faster to produce, and protect against virulence factors and antibiotic resistance genes. They improve immune system maturation and treat allergies. Postbiotics have clear chemical structures, long shelf lives, and safe doses. They imitate probiotic health advantages without live germs, making them a safer alternative to live probiotics.

Classification of postbiotics

Enzyme synthesis, carbohydrate fermentation, and vitamin and peptide synthesis are postbiotics. Proteins, organic acids, lipids, carbohydrates, vitamins, and complex compounds comprise postbiotics. SCFAs, plasminogen, teichoic acids, vitamins, peptides, and enzymes are postbiotics.

 Postbiotic’s extraction

Metabolomics quantifies micro molecules in complex biological systems, making it perfect for postbiotic detection. Centrifugation and ultrafiltration are the most common ways to extract postbiotics. Proteolytic microorganisms start lab fermentations to maintain pH and optimize postbiotic release.

References

Rafique N, Jan SY, Dar AH, Dash KK, Sarkar A, Shams R, Pandey VK, Khan SA, Amin QA, Hussain SZ. Promising bioactivities of postbiotics: A comprehensive review. Journal of Agriculture and Food Research. 2023 Jul 11:100708.

Provided by: Dr. Babak Tamizifar

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Some Vitamins Categorized as a Prebiotic

The International Scientific Association for Probiotics and Prebiotics (ISAPP) has been redefined prebiotics in 2017. They suggested that some vitamins were included in the category of prebiotics. Vitamins, as organic components, are usually present in foods instead of synthesized in sufficient quantities by the host and can play fundamental role in mediating biological processes in microbes, maintaining microbial homeostasis and intestinal barrier integrity and so, may have a potential use as prebiotics. Vitamins can be divided into two categories: lipophilic vitamins; consisting of vitamin A, D, E and K, and hydrophilic vitamins, which include vitamin B and C.

The effects of fat soluble vitamins on microbiota

Vitamin D is one of the most studied vitamins in the context of gut microecology. Some studies have demonstrated that the composition and diversity of gut microbes are strongly affected by vitamin D deficiency. For example, in an interventional, open-label pilot study, vitamin D3 supplementation was found to decrease the relative abundance of Proteobacteria while increasing that of Bacteroidetes (1). Furthermore, Guida et al. (2) evaluated a diet deficient in vitamin D on a mice model and found thatthe abundance of Firmicutes, Verrucomicrobia and Bacteroidetes decreased. In addition to vitamin D, oral administration of some other vitamins has also been shown to affect the composition of gut microbes.
Tian et al. analyzed fecal samples from vitamin A sufficient and deficient mice and observed a higher
Firmicutes/Bacteroidetes (F/B) ratio in these mice, which is associated with various metabolic diseases (3).
On the contrary, another study found that feeding mice with low levels of vitamin E increased the
abundance of Firmicutes, resulting in a higher F/B ratio in the gut, whereas no significant differences were observed in mouse fed with high doses of vitamin E as compared to the control group (4). Vitamin K in human body usually taken from dietary supplements. Gut microbiota also possess the gene to synthesize vitamin K (5). Dietary vitamin K can be remolded by bacteria such as Eubacterium rectale, Bacillus subtilis and several Bacteroides species in the form of menaquinones, which are able to regulate gut microbiota. Since some genera of Bacteroides and Faecalibacterium lost the ability to synthesize menaquinones, they have to utilize menaquinones made by nearby bacteria as growth factors for themselves (6).

The effects of water soluble vitamins on microbiota

Vitamin B12 may make a contribution in shaping the structure and function of human gut microbial communities through altering the corrinoid profile (7). Oral vitamin B12 supplement may also selectively deplete Bacteroides in C57BL/6 mice (8). This difference suggests that different types of vitamins and different doses of the same vitamin may have different regulatory effects on gut microbes. Specific screening of vitamins and next generation of probiotics (NGPs) is necessary to establish the mechanism by which vitamins affect the gut microbiota in order to determine which vitamins can be used as prebiotics for which NGPs.
Vitamin B2 (riboflavin) supplementation is critical for maintaining the abundance of Faecalibacteriome. Prausnitzii (F. P) in the gut microbiota. Although F. P adheres to the gut mucosa where oxygen diffuses from epithelial cells, it can employ an extracellular electron shuttle of riboflavin and thiols to transfer electrons to oxygen (9).

Provided by: Dr. Nazila Kassaian

Edited by: Marzieh Rahim khorasani

References:

 

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Gut microbiota and weight loss

Current evidence described gut microbiota dysbiosis is closely linked to obesity. In the treatment of obesity, a holistic approach including diet, pharmacotherapy, physical activity, bariatric surgery, and psychological support is recommended.

Weight-loss diets and gut microbiota

There is strong evidence that the Mediterranean or vegetarian/vegan diets are effective in promoting the optimal diversity and richness in beneficial bacteria. A vegetarian/vegan diet positively alters the gut microbiota through the development of a diverse and stable microbiome and Mediterranean diet is associated with increased levels of SCFAs. A Mediterranean diet has high levels of dietary fiber, n-3 fatty acids and polyphenols, as well as low levels of processed food. Data from research studies indicates that MD positively affects the GM by increasing the abundance of Bacteroidetes, Faecalibacterium prausnitzii, Clostridium (cluster XIVa), Bifidobacteria, and Lactobacilli, while decreasing the abundance of Firmicutes.

Microbiota manipulation and weight loss

The microbial-targeted therapies, including prebiotics, probiotics, and synbiotics, are considered adjuvant in obesity management. However there are different results, mainly because of the great heterogeneity of the studies because of different strains, interventional durations, doses, and forms. It is also unclear whether using these biotics accompanied by dietary intervention or bariatric surgery therapy will be more effective in obesity management in the short and long-term weight-loss maintenance.

The positive effects of lactobacillus probiotics on weight management has been reported.  Certain strains of Lactobacillus, such as L. Rhamnosus, L. Plantarum, L. Paracasei, and L. Gasseri, have shown some promising anti-obesity effects. While there is abundant evidence of the effect of supplementation of probiotics treatments, it is also important to acknowledge that not all mentioned studies have shown significant outcomes. This implies that studies with larger sample sizes and longer observation periods are necessary, and more extensive investigation of probiotics supplementation is needed to gain more knowledge. While microbiome-based medicines have made remarkable progress in the last decade from prebiotics and probiotics to live bio therapeutics for the weight management, there are still safety concerns and regulatory issues to be addressed.

Fecal microbiota transplant

The fecal microbiota transplant (FMT) is currently experimental and lacks authorization, posing numerous ethical, legal, and social challenges that must be resolved as part of an effective regulatory policy response. Frozen feces, freeze-dried stool, and more advanced items such as capsules containing synthetic stool generated in culture and assembled are all examples of the wide range of products of FMT treatment. Due to the risks associated with incorrect donor screening and unsatisfactory patient follow-up, any regulatory outcome that restricts access by either reducing supply or significantly increasing the cost of therapy should be implemented with extreme caution.

Next-Generational Probiotics (NGPs)

NGPs are composed of live bacteria and can be used to treat or prevent obesity. While established probiotic and microbiome research facilities can investigate NGPs, commercially motivated start-up biotechnology organizations or pharmaceutical firms are more likely to study Live Bio therapeutic Products.

prepared by: Nazila Kassaian, Marzieh Rahim khorasani

References

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The Effects of Prebiotics and Probiotics on Inflammatory Bowel Disease

prebioticsProbiotics-Featured-Image

The human intestine is colonized by 10–۱۰۰ trillion commensal bacteria that are involved in the digestion process, modulation of immune response, and other functions. Nowadays, due to excessive use of antibiotics, stress conditions, and hygiene, we encounter gut dysbiosis.

Prebiotics

Prebiotics are defined as a “substrate that is selectively utilized by host microorganisms conferring a health benefit”.

In order to be categorized as a prebiotic, a product must meet several conditions:

  • It should stimulate the proliferation and activity of some beneficial strains of gut bacteria
  • It should create a favorable medium to some beneficial bacteria in the colon
  • It should be resistant to the action of digestive enzymes and process of hydrolysis
  • It should not be absorbable in the upper digestive tract
  • It should not be destroyed during the food processing process
  • It should decrease the pH in the intestinal lumen

Research data demonstrate that prebiotics determine the change of gut microbiota spectrum and bacteria metabolites. However, there are still few data published regarding prebiotics in IBD. To date, results of prebiotic research in patients with IBD are conflicting. Although the administration of prebiotic agents may be associated with some adverse digestive side effects in active IBD, their administration in early childhood for a proper development of gut microbiome and later prevention of IBD onset should be taken into consideration.

probiotics

Probiotics

Probiotics are live organisms that are beneficial for the gut by modulating the immune response, increase the IgA production and enhance the host immune system`s defenses. Also, they are able to compete with pathogens.

The favorable actions of probiotics on human gut are the following:

  • Change of intestinal pH
  • The production of components with antibacterial activity (e.g., lactic acid, bacteriocins, hydroperoxides)
  • Competition for essential nutrients
  • Competitively block the binding sites on the epithelial cells and upregulate tight junction molecules of the mucosal barrier
  • The degradation of the receptors for toxins

Lactic-acid-producing bacteria (LAB) include the biggest part of gut microbiota, which produce lactic acid as a result to the anaerobic digestion of saccharides. Lactobacillus spp. are the most important group of bacteria found in fermented food (e.g., pickles, soured milk, kefir) and are considered to be beneficial for humans.

ibd

In case of IBD patients, there is an abnormal activation of the immune system due to chronic intestinal inflammation. The use of probiotics may help the transition from a pro-inflammatory to an anti-inflammatory state at the gut level. Nowadays, the strains currently available as probiotics are represented by the Bifidobacterium species, Lactobacillus strains, Bacillus species, Enterococcus faecium, Saccharomyces boulardii, and Pediococcus, which have been demonstrated to be associated with the beneficial health effects. Probiotic engineering determines the formation of bacterial strains with more powerful properties to target the enteric pathogens and to specifically intervene in the disease. This strategy uses bacteria or yeasts genetically engineered with the genes for some therapeutic agents that are acting as anti-inflammatory agents.

References:

Provided by Dr. Nazila Kassaian

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Gut-microbiota manipulation

gut microbiome

Nowadays, some strategies like probiotics, prebiotics, post biotics, synbiotics or fecal microbiota transplantation (FMT) rely on adding individual, several, or a whole consortium of living microbial organisms to exclude disease-causing microbes and provide health-promoting benefits. Moreover, bacteriocins and bacteriophages present another potential strategies to remove specific pathogens associated with the onset of a particular diseases; however, their exploration as therapeutics in humans is still in its infancy.

Gut-microbiota targeted therapeutics in IBD

The therapeutic potential of these agents in inflammatory bowel disease (IBD) comprising ulcerative colitis (UC) and Crohn’s disease (CD), has been evaluated in a meta-analysis of 32 randomized controlled trials (RCTs). The authors found that these therapeutics considerably increased the number of beneficial intestinal bacteria (particularly Bifidobacterium), induced or maintained IBD remission and lowered UC disease activity index whilst not affecting IBD recurrence. Subgroup analyses showed that combining probiotics and prebiotics with conventional therapies was more effective in reducing these parameters than traditional treatments alone, while synbiotic treatment seemed to be more effective than prebiotics and probiotics alone. Additionally, the study suggested that probiotics containing Bifidobacterium, Lactobacillus, or more than one bacterial strain were more effective as IBD therapeutics and proposed doses from 10۱۰ to 10۱۲ colony forming units (CFU)/day as reference dose. The severity of inflammation and disease activity has also been proposed to influence the effectiveness of microbiota-targeted therapeutics in IBD.

Moreover, the data could suggest that the microbiota-modulatory efficacy of prebiotics decreases going from healthy, at-risk subjects to those with inactive and active IBD, indicating their potential in IBD primary prevention and treatment in a less inflamed gut.

Gut-microbiota targeted therapeutics in diarrhea

The effect of probiotics on chronic diarrhea, associated with different intestinal disorders like irritable bowel syndrome (IBS) and functional diarrhea, was evaluated. Yang et al have shown that intake of Lactiplantibacillus plantarum CCFM1143 for 4 weeks can be effective in managing chronic diarrhea symptoms in patients compared to placebo (maltodextrin). Moreover, it has been demonstrated that prebiotic consumption decreases the abundance of Bacteroides and Eggerthella, increases the abundance of beneficial species like Akkermansia, Terrisporobacter, and Anaerostipes, and stimulates acetic and propionic acid production. These data suggesting the potency of this probiotic strain and prebiotic can improve the microbiota imbalance and clinical symptoms in functional bowel disorders.

Gut-microbiota targeted therapeutics in Helicobacter pylori infection

The therapeutic potential of probiotics alone or in combination with standard treatments has also been evaluated in Helicobacter pylori infection. One study showed that consumption of a probiotic drink containing fermented milk with Lacticaseibacillus paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690, and four yogurt strains for 28 days induced faster gut microbiota recovery after H. pylori eradication, reducing the abundance of potentially pathogenic bacteria (e.g., Escherichia-Shigella and Klebsiella) and increasing fecal SCFA generation compared to the control drink. Another study evaluated the therapeutic effects of a probiotic including Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus, provided alone or in combination with quadruple eradication therapy (PPI, bismuth, and two antibiotics) for 2 weeks, on gastric microbiota recovery in H. pylori-infected individuals. Results showed that 2 months after treatment, the quadruple therapy did not restore gastric microbiota of H. pylori-positive subjects to an uninfected state; however, adjuvant probiotic therapy contributed to its recovery by improving microbial diversity, reducing the abundance of potentially harmful bacteria (e.g., Fusobacterium, Campylobacter and Proteobacteria) and increasing the beneficial bacteria (e.g., Lachnospiraceae, Ruminococcaceae, Eubacterium ventriosum). By contrast, probiotic monotherapy was ineffective in H. pylori abolition and failed to restore gastric microbiota, with observed alterations in microbiota structure, increased putative pathogenic bacteria, and no induction of beneficial bacteria.

written by: Dr.Nazila Kassaian

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The effects of probiotics on modulation of microRNAs

The effects of probiotics on modulation of microRNAs

MicroRNAs (miRNAs) are short non-coding RNAs comprising 20 to 24 nucleotide bases, which play important roles in all the biological and physiological pathways in multicellular organisms. Figure 1 shows the scheme of miRNA biogenesis. Dysregulation of microRNAs plays an important role in the pathogenesis of many different diseases. These diseases include, central nervous system disorders, autoimmune diseases, cancers and many other common diseases worldwide. Some treatments that are used to cure these diseases act by influencing gene expression and affecting miRNA regulation.

The effects of probiotics on modulation of microRNAs

Probiotics are among other biological factors that have recently been discussed with regard to whether they have any effects on miRNAs. Many laboratory studies have so far been done to investigate the effects of probiotics on miRNAs.

In one study by Heydari et al. supplementation with Lactobacillus acidophilus and Bifidobacterium bifidum probiotics in a mouse model of azoxymethane (AOM) induced colon cancer was investigated. The results showed that the expression levels of miR-135b, miR-155, and KRAS (one of the target genes of these miRNAs) increased after azoxymethane cancer induction, and administration of a probiotic preparation containing Lactobacillus acidophilus and Bifidobacterium bifidum decreased the above mentioned factors. Conversely, cancer induction with azoxymethane reduced the expression of miR-26b, miR-18a, APC, PU.1, and PTEN in mice, and probiotic supplementation increased them again. It seems that Lactobacillus acidophilus and Bifidobacterium bifidum though increasing the expression of the tumor suppressor miRNAs and their target genes and decreasing the oncogenes can improve colon cancer treatment.

Enterococcus faecium NCIMB 10415 is a probiotic species that has been shown to affect the intestinal microbial flora, and improve the immune system response in numerous human and animal studies. In one in vitro study using next-generation sequencing, Kreuzer-Redmer and colleagues analyzed the differential expression of the miRNAs and potential target genes in the ileal and jejunal lymphatic tissue isolated from piglets which had been fed with E. faecium NCIMB 10415 versus control animals. They found that feeding E. faecium affected the expression of miR-423-5p as well as regulating its target gene IGLC. Therefore, E. faecium benefits the immune cells in the small intestine probably by affecting the expression of miR-423-5p.

Escherichia coli Nissle 1917 (EcN) is a non-pathogenic Gram-negative bacterium of the Enterobacteriaceae family, which when used as a probiotic, has beneficial effects on human health. In one in vitro study, E. coli (EPEC) pathogenic strain E2348/69 and E. coli Nissle 1917 (EcN) were tested in human T84 and THP-1 cells to compare the effects of the two strains on cytokine and miRNA expression. EcN increased the expression of CXCL1 and IL-8 in human T84 epithelial cells infected from the basolateral side. miR-146a is a molecular adaptor in the Toll-like receptor (TLR)/NF-κB signaling pathway. In this study, miR-146a was increased in T84 and THP-1 cells treated with EPEC, but this increase was less pronounced when these cells were incubated with EcN. Two miR-146a target genes were also identified, including IRAK1 and TRAF6. So, the probiotic EcN induced the expression of miR-146a in epithelial and immune cells, though this induction was reduced by incubation with pathogenic strain EcN.r.

prepared by: Laleh Hoveyda

Reference

Davoodvandi A, Marzban H, Goleij P, Sahebkar A, Morshedi K, Rezaei S, Mahjoubin-Tehran M, Tarrahimofrad H, Hamblin MR, Mirzaei H. Effects of therapeutic probiotics on modulation of microRNAs. Cell Commun Signal. 2021 Jan 11;19(1):4. doi: 10.1186/s12964-020-00668-w. PMID: 33430873; PMCID: PMC7798223.

 

 

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The Role of Probiotics in the Prevention and Management of Age-Related Diseases

probiotics and aging

The prevalence of elderly, is expected to double by 2050. Scientific advancements in the prevention and treatment of disease have prolonged human life span however, the increased life span is not accompanied by an elevated health span. Aging is an irreversible biological process that can be defined using nine hallmarks: the deregulation of genetic, epigenetic, and immunological mechanisms (immune senescence), as well as mitochondrial dysfunction, cell senescence, stem cell exhaustion and faulty nutrient sensing and intercellular signaling. In this context, several recent studies suggest that the aging microbiome presents abnormally high instability and heterogeneity between hosts, while specific microbial signatures of age-related diseases have started to be revealed. Furthermore, increased gut permeability can amplify low-grade local and systemic inflammation, predisposing individuals to the onset of multi morbidity. Several studies have proposed that the intake of probiotics can fine tune the gut microbial composition to more favorable structures in a host-specific manner.

 Probiotics and Aging

Cell senescence and the exhaustion of the regenerative mechanisms result in loss of tissue functionality, thus providing fertile ground for the onset of multi morbidity. Apart from cancer, neurodegenerative and musculoskeletal disorders; cardiovascular and metabolic disease also present with high frequencies in this demographic, as aging is a major risk factor for chronic inflammatory diseases, such as diabetes and atherosclerosis. In this context, cell senescence and telomere shortening in cardiac cells lead to the progressive degeneration of aortic valves and vascular cells, increasing risk for the incidence of stroke and cardiac arrest. Interestingly, the gut microbiota can present differences between pre diabetic and healthy individuals, as shown during the integrative human microbiome project. Indeed, it was found that insulin-resistant participants exhibited a specific metabolic profile, delayed inflammatory responses, and altered gut microbiome structure compared to insulin-sensitive participants. Importantly, this multilevel approach was efficient in pinpointing disease states prior to clinical manifestations.

New investigations

Refining Probiotic Research in the Elderly Aging is highly personalized process, and thus the genetic, metabolic and microbial signature of advanced age could differ between individuals. The results of novel studies may provide a basis for the differential pace of aging recorded in individuals, as well as the onset of (multi-)morbidity with age. The genetic component of age-related diseases was examined in a recent study, where it was found that diseases that present with late onset in the population, share a common genetic basis. Indeed, there is significant overlap between diseases in terms of loci implicated in longevity. The role of the gut microbiome in ageing is currently a hot topic of study. Microbial residents of the gut co-evolve with the host throughout life. The structure of the gut microbiome is stabilized at around three years of age; during adulthood the composition and function of these communities remain relatively stable, as they can be influenced by a plethora of genetic and environmental factors. Disease-specific microbial signatures during adulthood have been proposed by several studies, however in the case of aging, the gut microbiome undergoes tremendous changes leading to dysbiosis. A shared characteristic of the aging gut microbiome is that the diversity of the microbiome falls dramatically, presenting high inter individual variability. This new unstable composition favors the establishment and proliferation of pathobionts, such as Proteobacteria . These changes can trigger local and systemic inflammation, while also contributing to the weakening of the gut barrier integrity. More specifically, the population shifts result in changes in the metabolic profile of the gut microbiome. For instance, decrease in the populations of short-chain fatty acid (SCFA) producers, such as Akkermansia muciniphila, results in decreased production of acetate, butyrate and propionate, which display anti-inflammatory activity and preserve the function of the gut mucosa. It is important to note however, that these changes may not be exclusively associated to aging, but also to environmental factors, use of medications (for co-morbid diseases/antibiotics), as well as malnutrition. The gut microbiome can be easily manipulated extrinsically; however, the ability of probiotics to alter its structure and function is debatable. Studies on healthy adults have shown that the gut microbiome presents an individual-specific resistance to the colonization of probiotics that may be decreased after antibiotic treatments. Nevertheless, their ability to rehabilitate the structure and function of the gut microbiome is limited and may even have adverse effects by slowing down the full repopulation of the gut. In this light, the fact that the aged microbiome presents a decreased diversity could indicate that probiotic supplementation could more readily modify the gut microbiome. Undoubtedly, the integration of systems biology in probiotic research has unraveled the great complexity of their biological properties, also providing an explanation for contradicting clinical data and inconsistencies of clinical outcomes in individuals.

 Conclusions

 As the worldwide population is ageing rapidly, the need for expanding citizen health span is coming to the forefront. Age is considered an important risk factor for the development of debilitating disease that can increase the dependency of individuals and negatively affect their quality of life. The biological mechanisms of aging are starting to be revealed, and novel approaches, for more efficient management of multi morbidity have been developed. Probiotics that can modulate the root causes of aging, especially inflammation, oxidative stress and cell senescence could comprise useful tools in this direction. Despite the available literature on the beneficial effects of probiotic consumption on age-related diseases, no consensus has been reached for their use in clinical practice. This phenomenon could be attributed to the absence of meticulous characterization of the biology and mechanisms of action of probiotic strains that can enhance the lack of translatability of preclinical studies. Furthermore, current clinical studies present analytical drawbacks that can weaken their arguments and conclusions. With the dawn of the multi-omics era, the use of high throughput platforms to understand the complex host–microbiome–probiotic interactions, could enhance the efficacy and safety of probiotic consumption in the elderly. Conclusively, clinical studies with greater rigor and proper measurement of outcomes to evaluate and systematically classify the holistic effects of probiotic consumption, are required in order to design personalized approaches for the management of age-related disease.

prepared by: Nazila Kassaian

references

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The role of the microbiota in the management of intensive care patients

The role of the microbiota in the management of intensive care patients

In the gut, the microbiota mostly comprised bacteria, but it also harbors archaea, viruses, protozoans, and fungi. The composition of the gut microbiota is unique to each individual in that the gut microbiota of two given individuals consistently show differences in their composition. Nonetheless, it is also highly dynamic and evolves throughout life under the influence of a wide diversity of genetic, environmental, medical, and dietary determinants.

The microbiota and intensive care patients

In the intensive care setting, the gut microbiota of patients is submitted to various stresses including antibiotic exposure, modification of gastrointestinal transit, artificial nutrition or sepsis which may lead to a dysbiosis during hospitalization. Indeed, the gut microbiota in critically ill patients appears to be different from that of healthy subjects, demonstrating markedly lower richness and diversity, and the near replacement of commensal genera by opportunistic pathogens. Recent evidence has shown that dysbiosis in ICU patients might have consequences on survival, stressing that dysbiosis could be considered as an authentic, organ-failure-affecting prognosis along with renal, cardiac, or respiratory failures.

Dysbiosis alteration and patients’ management

The gut microbiota mainly includes difficult-to-cultivate anaerobic bacteria, hence knowledge about its composition has significantly arisen from culture-independent methods based on next-generation sequencing (NGS) such as 16S profiling and shotgun metagenomics.

Correcting the microbiota disturbances to avoid their consequences is now possible. Fecal microbiota transplantation is recommended in recurrent C. difficile infections and microbiota-protecting treatments such as antibiotic inactivators are currently being developed. The growing interest in the microbiota and microbiota-associated therapies suggests that the control of the dysbiosis could be a key factor in the management of critically ill patients.

The gut microbiota is also the main reservoir for multidrug-resistant bacteria organisms (MDRO). Initially kept at low intestinal concentrations as a consequence of the barrier effect exerted by commensal anaerobic bacteria, they may bloom after antibiotic exposure and increase the risk their involvement in further infections.

prepared by: Nazila Kassaian

Reference

Szychowiak P, Villageois-Tran K, Patrier J, Timsit JF, Ruppé É. The role of the microbiota in the management of intensive care patients. Ann Intensive Care. 2022 Jan 5;12(1):3. doi: 10.1186/s13613-021-00976-5. PMID: 34985651; PMCID: PMC8728486.

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A mini review on Probiotics, prebiotics, Postbiotcs, Paraprobiotics and synbiotics

Probiotics, prebiotics, Postbiotcs, Paraprobiotics and synbiotics

Scientific use of probiotics, postbiotics, prebiotics, paraprobiotics and synbiotics can be safe and alternative strategy against microbial infections, particularly in the ongoing and post-pandemic situation. Probiotics are known to promote heath by stimulating native gut microbiota, host immunity, cholesterol reduction and several other functions, whereas their metabolites such as bacteriocins, lactic acid and hydrogen peroxide, also known as postbiotics, secreted by these microorganisms can be of immense importance as antimicrobials against a broad range of pathogenic bacteria. A relatively new form of product has been discovered to replace the live probiotics by inactivated or heat-killed probiotic cells known as paraprobiotics. It has shown potent applications for the treatment of several diseases including viral infections. Prebiotics are generally food ingredients which not only promote the growth of probiotic microorganisms present in the human gut, but also stimulate the immune system. Moreover, use of fermented foods, the natural habitat of probiotic bacteria, is of immense importance which eventually helps in the better treatment of several diseases, including gut related disorders.

Health benefits and therapeutic potentials

The importance of probiotics for human health has been established since long past. But study on the role of prebiotics, synbiotics and other derivatives is still at nascent stage. Looking at the current scenario of pandemics, the emphasis has been given on antimicrobial potential of probiotics against pathogenic microorganisms and host immunity. Interestingly, gut microbiota (GM) has been proposed as a “forgotten organ” which is tirelessly involved with other organs in establishing a bi- or multidirectional communications is also discussed in addition to cancer. Therefore, the roles of probiotics in modulation of host immune system and gut microbiota, treatment of infection, inflammatory bowel diseases (IBD) and cancer have been elaborated.

Conclusions and future perspectives

Probiotic bacteria positively affect the human health by stimulating immune system and inhibition of pathogens. Due to their multifarious health benefits, there has been a significant interest in probiotics and prebiotics in healthcare and consumer products. However, an extensive study data is limited to a few probiotics and prebiotics. Various clinical studies have supported the role of probiotics and prebiotics alone and in combination (synbiotics) with each other in the treatment and prevention a large number of life-threatening diseases including cancer, HIV infection, gut diseases and many more. There are sufficient evidences that probiotics and their derivatives may also pay significant role in the management of COVID19. Therefore, an utmost need of an hour is to clinically validate some more probiotics and prebiotics along with synbiotics for human health and therapeutic applications. Modern techniques based on molecular biology, genetic engineering, system biology, multiomics, nanotechnology and immunology must be utilized for thorough understanding of structure and function of microbiome with respect to probiotics and prebiotics. These studies will help in understanding the interaction among human body functions and microbiome. Therefore, scientists from different fields (academic institutions, clinicians and industries) should come together and join hands in this direction through a collaborative translational research attempting to directly relate insights from the lab to the manufacturers, the consumers and the clinicians.

prepared by: Nazila Kassaian

References

Yadav MK, Kumari I, Singh B, Sharma KK, Tiwari SK. Probiotics, prebiotics and synbiotic: Safe options for next-generation therapeutics. Applied Microbiology and Biotechnology. 2022 Jan 11:1-7.

Gayathri D, Vasudha M, Prashantkumar CS. Gut-Brain Axis: Probiotic Interactions and Implications for Human Mental Health. InMicrobiome-Gut-Brain Axis 2022 (pp. 261-280).

Samtiya M, Dhewa T, Puniya AK. Probiotic Mechanism to Modulate the Gut-Brain Axis (GBA). InMicrobiome-Gut-Brain Axis 2022 (pp. 237-259).

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AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders

AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders

The most accepted definition of probiotics is “live microorganisms which when administered inadequate amounts confer a health benefit on the host”. The health benefits of probiotics on gut microbiome have been previously described. The effects of probiotic can be species-, dose-, and disease-specific. Probiotics have been widely studied in a variety of gastrointestinal diseases. However, lack of clear guidelines on the most effective probiotic for different gastrointestinal conditions may be confusing.

Method

The AGA process for developing clinical practice guidelines follows the GRADE approach and best practices as outlined by the National Academy of Science.

PICO (Participants, intervention, comparison, and outcomes) format questions were identified and formulated about the use of probiotic formulations for the prevention and treatment of gastrointestinal diseases (not prebiotic use).

In the current guidelines following gastrointestinal disorders (Clostridioides difficile associated diseases, inflammatory bowel disease, irritable bowel syndrome, infectious gastroenteritis, and necrotizing enterocolitis) were considered.

 The target audience for this guideline includes healthcare providers, dieticians,   and patients. The guidelines include recommendations for specific populations including adults, children and neonates.

Recommendations

  1. In patients with C. difficile infection, we recommend the use of probiotics only in the context of a clinical trial.
  2. In adults and children on antibiotic treatment, we suggest the use of S. boulardii; or the two-strain combination of L. acidophilus CL1285 and L. casei LBC80R; or the three-strain combination of L. acidophilus, L. delbrueckii subsp. bulgaricus, and B. bifidum; or the four-strain combination of L. acidophilus, L. delbrueckii subsp. bulgaricus, B. bifidum, and S. salivarius subsp. thermophilus over no or other probiotics for prevention of C. difficile infection.
  3. In adults and children with Crohn’s disease, we recommend the use of probiotics only in the context of a clinical trial.
  4. In adults and children with ulcerative colitis, we recommend the use of probiotics only in the context of a clinical trial.
  5. In adults and children with pouchitis, we suggest the eight-strain combination of L. paracasei subsp. paracasei DSM 24733, L. plantarum DSM 24730, L. acidophilus DSM 24735, L. delbrueckii subsp. bulgaricus DSM 24734, B. longum subsp. Longum DSM 24736, B. breve DSM 24732, B. longum subsp. infantis DSM 24737, and S. salivarius subsp. thermophilus DSM 24731 over no or other probiotics.
  6. In symptomatic children and adults with irritable bowel syndrome, we recommend the use of probiotics only in the context of a clinical trial.
  7. In children with acute infectious gastroenteritis, we suggest against the use of probiotics.
  8. In preterm (less than 37 weeks GA), low birth weight infants, we suggest using a combination of Lactobacillus spp. and Bifidobacterium spp. (L. rhamnosus ATCC 53103 and B. longum subsp. infantis; or L. casei and B. breve; or L. rhamnosus, L. acidophilus, L. casei, B. longum subsp. infantis, B. bifidum, and B. longum subsp. longum; or L. acidophilus and B. longum subsp. infantis; or L. acidophilus and B. bifidum; or L. rhamnosus ATCC 53103 and B. longum Reuter ATCC BAA-999; or L. acidophilus, B. bifidum, B. animalis subsp. lactis, and B. longum subsp. longum), or B. animalis subsp. lactis (including DSM 15954), or L. reuteri (DSM 17938 or ATCC 55730), or L. rhamnosus (ATCC 53103 or ATC A07FA or LCR 35) for prevention of NEC over no and other probiotics.

Key Words

Probiotics, Gastrointestinal Disorders, Guideline

Reference

Su GL, Ko CW, Bercik P, Falck-Ytter Y, Sultan S, Weizman AV, Morgan RL. AGA Clinical Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology. 2020 Aug;159(2):697-705. doi: ۱۰.۱۰۵۳/j.gastro.2020.05.059.