Commensal Microbes Research Articles

Gut microbiome-mediated mechanisms for reducing cholesterol levels: implications for ameliorating cardiovascular disease.

Cardiovascular disease (CVD) is a health problem worldwide, and elevated cholesterol levels are a key risk factor for the disease. Dysbiotic gut microbiota has been shown to be associated with CVD development. However, the beneficial effects of healthy microbiota in decreasing cholesterol levels have not been summarized. Herein, we begin by discussing the potential mechanisms by which the gut microbiota reduces cholesterol levels. We further sketch the application of probiotics from the genera Lactobacillus and Bifidobacterium in reducing cholesterol levels in clinical studies. Finally, we present the cholesterol-lowering function of beneficial commensal microbes, such as Akkermansia and Bacteroides spp., as these microbes have potential to be the next-generation probiotics (NGPs). The information reviewed in this paper will help people to understand how the gut microbiome might alter cholesterol metabolism and enable the development of NGPs to prevent and treat CVD.

504. Latent HHV7 Infection Attenuates Beneficial Host-Microbe Interactions in the Human Gut

Abstract Background Human Herpes Virus 7 (HHV7) infection results in a lifelong latent infection with over 95% of adults seropositive for HHV7. Lymphocytes are the best understood host cell type for latent HHV7, with the gastric mucosa another site of latent infection. Herpesviridae latency affects host processes like interferon signaling, antigen presentation, and proliferation—the same host pathways are implicated in the beneficial responses to commensal microbes. Methods Adult human colonic organoids with or without latent HHV7 infection were co-cultured with B. longum in asymmetric oxygen conditions that allow for live interaction (F1). The transcriptional state after 24h of interactions was determined with RNA-sequencing. The transcriptional state was compared between axenic (no microbes) or after co-culture and with or without latent HHV7. F1: Establishing oxygen gradients across epithelial monolayers (A) Schematic of oxygen gradient apparatus (B) Closeup view of individual well (C) Growth of the anaerobe B. longum was identical in the apparatus with hypoxic epithelial compared to full anaerobic growth (D) Butyrate administration protects the epithelium from inflammatory effects of deoxycholate. Results Screening human intestinal organoids (that lack lymphocytes and are strictly of the endodermal lineage) we have generated evidence that intestinal stem cells (ISC) and IEC can be a host cell for latent HHV7 infection in some but not all people (T1). RNA-sequencing reveals that this is true latency, with ISC and IEC containing HHV7 without transcripts from any of the protein-coding genes in the HHV7 genome. Further we have observed that latent HHV7 is mosaic in the gut, not affecting all of the ISC in an individual (T1). In organoid-derived human IEC we have noted co-culture with the commensal bacteria B. longum suppresses key executors of apoptosis and pyroptosis (F2). These same effects are no longer observed with the B. longum is interacting with IEC latently infected with HHV7. A similar pattern was observed with NFkB regulators (F3). T1: Latent HHV7 is found in some intestinal organoids derived from healthy adults From the University of Michigan Translational Tissue Modeling Laboratory (TTML) organoid registry. Each donor is assigned a unique numerical ID. Viral panel is from a commercial multiplex PCR screen. Notably, donor 87 has colonic organoids with and without latent HHV7. F2: Co-culture with the commensal microbe B. longum suppresses most apoptosis and pyroptosis executors only in an organoid without latent HHV7 infection. Fragments per kilobase per millions of reads (FPKM) from RNA-sequencing of fully-differentiated organoid-derived human intestinal epithelium after 24 hours of co-culture with B.longum (Orange) or remaining axenic (without microbes; Blue). Results from cell without (left) or with (right) latent HHV7. F3: Stimulation of the NFkB inhibitor NFKBIA by co-culture with the commensal microbe B. longum is absent in organoids with latent HHV7 infection. Fragments per kilobase per millions of reads (FPKM) from RNA-sequencing of fully-differentiated organoid-derived human intestinal epithelium after 24 hours of co-culture with B.longum (Orange) or remaining axenic (without microbes; Blue). Results from cell without (left) or with (right) latent HHV7. Conclusion Latent HHV7 in the human gut epithelium may attenuate the effect of beneficial microbes like B. longum (F4). The evidence for mosaicism of latent HHV7 in the human gut adds a spatial aspect to these attenuating effects that could be relevant for specific disease processes (e.g. skip lesions in Crohn’s disease). Confirmation of these findings, estimating the true prevalence of latent HHV7 in the gut, and identification of the HHV7 latency mechanism will be required to understand the full implications of these findings. F4: A Model of Latent HHV7 Infection Attenuating Responses to Commensal Microbes. Based on our findings, latent HHV7 infection in the intestinal epithelium may leave the gut mucosa at increased risk for injury by impairing the beneficial response to commensal microbes in a spatially complex manner due to the apparent mosaic nature of latent HHV7 infection in the gut. Disclosures Jonathan L. Golob, MD/PhD, Loxo Oncology: Employment of Spouse.

Origins of symbiosis: shared mechanisms underlying microbial pathogenesis, commensalism and mutualism of plants and animals.

Regardless of the outcome of symbiosis, whether it is pathogenic, mutualistic or commensal, bacteria must first colonize their hosts. Intriguingly, closely-related bacteria that colonize diverse hosts with diverse outcomes of symbiosis have conserved host-association or virulence factors. This review describes commonalities in the process of becoming host associated amongst bacteria with diverse lifestyles. Whether a pathogen, commensal or mutualist, bacteria must sense the presence of and migrate towards a host, compete for space and nutrients with other microbes, evade the host immune system, and change their physiology to enable long-term host association. We primarily focus on well-studied taxa, such as Pseudomonas, that associate with diverse model plant and animal hosts, with far-ranging symbiotic outcomes. Given the importance of opportunistic pathogens and chronic infections in both human health and agriculture, understanding the mechanisms that facilitate symbiotic relationships between bacteria and their hosts will help inform the development of disease treatments for both humans, and the plants we eat.

Delivery of streptomycin to the rat colon by use of electrospun nanofibers

Drug-loaded electrospun nanofibers are potential drug carrier systems that may optimize disease treatment while reducing the impact on commensal microbes. The feasibility of streptomycin-loaded pullulan nanofibers fabricated from a green electrospinning procedure using water as the solvent was assessed. We conducted a rat study including a group treated with streptomycin-loaded nanofibers (STR-F, n = 5), a group treated with similar concentrations of streptomycin in the drinking water (STR-W, n = 5), and a non-treated control group (CTR, n = 5). Streptomycin was successfully loaded into nanofibers and delivered by this vehicle, which minimized the quantity of the drug released in the ileal compartment of the gut. Ingested streptomycin-resistant E. coli colonized of up to 106 CFU/g feces, revealing a selective effect of streptomycin even when given in the low amounts allowed by the nanofiber-based delivery. 16S amplicon sequencing of the indigenous microbiota revealed differential effects in the three groups. An increase of Peptostreptococcaceae in the cecum of STR-F animals may indicate that the fermentation of nanofibers directly or indirectly promoted growth of bacteria within this family. Our results elucidate relevant properties of electrospun nanofibers as a novel vehicle for delivery of antimicrobials to the large intestine.

Gut microbiome in multiple myeloma: Mechanisms of progression and clinical applications.

The gut commensal microbes modulate human immunity and metabolism through the production of a large number of metabolites, which act as signaling molecules and substrates of metabolic reactions in a diverse range of biological processes. There is a growing appreciation for the importance of immunometabolic mechanisms of the host-gut microbiota interactions in various malignant tumors. Emerging studies have suggested intestinal microbiota contributes to the progression of multiple myeloma. In this review, we summarized the current understanding of the gut microbiome in MM progression and treatment, and the influence of alterations in gut microbiota on treatment response and treatment-related toxicity and complications in MM patients undergoing hematopoietic stem cell transplantation (HSCT). Furthermore, we discussed the impact of gut microbiota-immune system interactions in tumor immunotherapy, focusing on tumor vaccine immunotherapy, which may be an effective approach to improve anti-myeloma efficacy.

A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice

Interactions with commensal microbes shape host immunity on multiple levels and play a pivotal role in human health and disease. Tissue-dwelling, antigen-specific T cells are poised to respond to local insults, making their phenotype important in the relationship between host and microbes. Here we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics associated with innate-like T cells. This cell population is abundant and conserved in the human and murine colon and endowed with polyfunctional effector properties spanning classic Th1- and Th17-cytokines, cytotoxic molecules, and regulators of epithelial homeostasis. T cells with this phenotype are increased in ulcerative colitis patients, and their presence aggravates pathology in dextran sodium sulphate-treated mice, pointing towards a pathogenic role in colitis. Our findings add to the expanding spectrum of innate-like immune cells positioned at the frontline of intestinal immune surveillance, capable of acting as sentinels of microbes and the local cytokine milieu.

Viral infectious diseases severity: co-presence of transcriptionally active microbes (TAMs) can play an integral role for disease severity.

Humans have been challenged by infectious diseases for all of their recorded history, and are continually being affected even today. Next-generation sequencing (NGS) has enabled identification of, i) culture independent microbes, ii) emerging disease-causing pathogens, and iii) understanding of the genome architecture. This, in turn, has highlighted that pathogen/s are not a monolith, and thereby allowing for the differentiation of the wide-ranging disease symptoms, albeit infected by a primary pathogen. The conventional 'one disease - one pathogen' paradigm has been positively revisited by considering limited yet important evidence of the co-presence of multiple transcriptionally active microbes (TAMs), potential pathogens, in various infectious diseases, including the COVID-19 pandemic. The ubiquitous microbiota presence inside humans gives reason to hypothesize that the microbiome, especially TAMs, contributes to disease etiology. Herein, we discuss current evidence and inferences on the co-infecting microbes particularly in the diseases caused by the RNA viruses - Influenza, Dengue, and the SARS-CoV-2. We have highlighted that the specific alterations in the microbial taxonomic abundances (dysbiosis) is functionally connected to the exposure of primary infecting pathogen/s. The microbial presence is intertwined with the differential host immune response modulating differential disease trajectories. The microbiota-host interactions have been shown to modulate the host immune responses to Influenza and SARS-CoV-2 infection, wherein the active commensal microbes are involved in the generation of virus-specific CD4 and CD8 T-cells following the influenza virus infection. Furthermore, COVID-19 dysbiosis causes an increase in inflammatory cytokines such as IL-6, TNF-α, and IL-1β, which might be one of the important predisposing factors for severe infection. Through this article, we aim to provide a comprehensive view of functional microbiomes that can have a significant regulatory impact on predicting disease severity (mild, moderate and severe), as well as clinical outcome (survival and mortality). This can offer fresh perspectives on the novel microbial biomarkers for stratifying patients for severe disease symptoms, disease prevention and augmenting treatment regimens.

Microbiota-mediated reactivation of triclosan oxidative metabolites in colon tissues

Triclosan (TCS) is a widespread antimicrobial agent that is associated with many adverse health outcomes. Its gut toxicity has been attributed to the molecular modifications mediated by commensal microbes, but microbial transformations of TCS derivatives in the gut lumen are still largely unknown. Aromatic hydroxylation is the predominant oxidative metabolism of TCS that linked to its toxicological effects in host tissues. Here, we aimed to reveal the biological fates of hydroxyl-TCS (OH-TCS) in the colon, where intestinal microbes mainly reside. Unlike the profiles generated via host metabolism, OH-TCS species remain unconjugated in human stools from a cohort study. Through tracking molecular compositions in mouse intestinal tract, elevated abundance of free-form OH-TCS while reduced abundance of conjugated forms was observed in the colon digesta and mucosa. Using antibiotic-treated and germ-free mice, as well as in vitro approaches, we demonstrate that gut microbiota-encoded enzymes efficiently convert glucuronide/sulfate-conjugated OH-TCS, which are generated from host metabolism, back to their bioactive free-forms in colon tissues. Thus, host-gut microbiota metabolic interactions of TCS derivatives were proposed. These results shed light on the crucial roles of microbial metabolism in TCS toxicity, and highlight the importance of incorporating gut microbial transformations in health risk assessment of environmental chemicals.

200 Optimised 3D skin models incorporating microbiome and host immune responses

Commensal microbes and humans have coevolved toward a symbiotic relationship. In healthy individuals, the human microbiome has a vital role in the development of the innate and adaptive immune system, inducing protective and regulatory immunity, and the immune system maintains an optimal balance of microbes. Several acute and chronic skin conditions are a result of imbalances in the host-microbiome relationship and are accompanied by epidermal barrier disruption. This research aims to develop three-dimensional (3D) in vitro skin models integrating microbiology and immune cells to simulate this complex relationship and the effects on epidermal health.

IMMU-32. SPERMIDINE DRIVES GLIOBLASTOMA PROGRESSION VIA SELECTIVE MODULATION OF THE IMMUNE SYSTEM

Abstract Glioblastoma (GBM) is incurable despite aggressive standard of care treatments (maximal safe surgical resection, radiation, chemotherapy). GBM therapeutic resistance is due to multiple factors, including tumor heterogeneity and a highly immunosuppressive environment. Naturally occurring polyamines have been identified as a putative therapeutic target in other cancers based on their increased presence and function in normal conditions; they are critical for cell growth and proliferation and cellular functions including autophagy and apoptosis. While polyamines are increased in GBM patients, little is known about their impact on GBM growth. In syngeneic immune competent mouse glioma models (GL261, SB28), mass spectrometry data revealed that spermidine (SPD) – a member of the polyamine family – is increased in tumor tissue as compared to non-neoplastic control brain tissue (sham implanted animals). To test the impact of SPD on tumor growth, we treated mouse glioma models with exogenous SPD and found treatment significantly decreased survival. However, in immunocompromised host mice, no such difference was observed, indicating the mechanism through which SPD is driving GBM progression likely involves immune system alterations. Depletion of myeloid derived suppressor cells in vivo via anti-Gr-1 antibody rescues the decrease in survival caused by exogenous SPD, indicating that SPD drives GBM by affecting immune-suppressive cell subsets, namely MDSCs. To assess if SPD is associated with more aggressive GBM growth in human patients, we are currently analyzing polyamine levels in human GBM samples of long vs short term survivors. We are also exploring the effect of dietary polyamines on GBM via the gut-brain-microbiome axis, as polyamines are enriched in many foods and produced by a subset of commensal gut microbes. Understanding the interactions between polyamines, the tumor microenvironment, and the immune response provide a new mechanism for GBM regulation and identify opportunities to alter the environment in the body to enhance immunotherapeutic efficacy.

Toll-like receptor 4 and lipopolysaccharide from commensal microbes regulate Tembusu virus infection

Unlike most flaviviruses transmitted by arthropods, Tembusu virus (TMUV) is still active during winter and causes outbreaks in some areas, indicating vector-independent spread of the virus. Gastrointestinal transmission might be one of the possible routes of vector-free transmission, which also means that the virus has to interact with more intestinal bacteria. Here, we found evidence that TMUV indeed can transmit through the digestive tract. Interestingly, using an established TMUV disease model by oral gavage combined with an antibiotic treatment, we revealed that a decrease in intestinal bacteria significantly reduced local TMUV proliferation in the intestine, revealing that the bacterial microbiome is important in TMUV infection. We found that lipopolysaccharide (LPS) present in the outer membrane of Gram-negative bacteria enhanced TMUV proliferation by promoting its attachment. Toll-like receptor 4 (TLR4), a cell surface receptor, can transmit signal from LPS. We confirmed colocalization of TLR4 with TMUV envelope (E) protein as well as their interaction in infected cells. Coherently, TMUV infection of susceptible cells was inhibited by an anti-TLR4 antibody, purified soluble TLR4 protein, and knockdown of TLR4 expression. LPS-enhanced TMUV proliferation could also be blocked by a TLR4 inhibitor. Meanwhile, pretreatment of duck primary cells with TMUV significantly impaired LPS-induced interleukin 6 production. Collectively, our study provides first insights into vector-free transmission mechanisms of flaviviruses.

A Review of Immunomodulatory Reprogramming by Probiotics in Combating Chronic and Acute Diabetic Foot Ulcers (DFUs).

Diabetic foot ulcers (DFUs) are characterized by a lack of angiogenesis and distal limb diabetic neuropathy. This makes it possible for opportunistic pathogens to protect the biofilm-encased micro-communities, causing a delay in wound healing. The acute and chronic phases of DFU-associated infections are distinguished by the differential expression of innate proinflammatory cytokines and tumor necrosis factors (TNF-α and -β). Efforts are being made to reduce the microbial bioburden of wounds by using therapies such as debridement, hyperbaric oxygen therapy, shock wave therapy, and empirical antibiotic treatment. However, the constant evolution of pathogens limits the effectiveness of these therapies. In the wound-healing process, continuous homeostasis and remodeling processes by commensal microbes undoubtedly provide a protective barrier against diverse pathogens. Among commensal microbes, probiotics are beneficial microbes that should be administered orally or topically to regulate gut-skin interaction and to activate inflammation and proinflammatory cytokine production. The goal of this review is to bridge the gap between the role of probiotics in managing the innate immune response and the function of proinflammatory mediators in diabetic wound healing. We also highlight probiotic encapsulation or nanoformulations with prebiotics and extracellular vesicles (EVs) as innovative ways to tackle target DFUs.

Investigating dysbiosis and microbial treatment strategies in inflammatory bowel disease based on two modified Koch's postulates.

Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease that occurs in the intestinal tract. It is mainly divided into two subtypes, i.e., the Crohn's disease (CD) and ulcerative colitis (UC). At present, its pathogenesis has not been fully elucidated, but it has been generally believed that the environment, immune disorders, genetic susceptibility, and intestinal microbes are the main factors for the disease pathogenesis. With the development of the sequencing technology, microbial factors have received more and more attention. The gut microbiota is in a state of precise balance with the host, in which the host immune system is tolerant to immunogenic antigens produced by gut commensal microbes. In IBD patients, changes in the balance between pathogenic microorganisms and commensal microbes lead to changes in the composition and diversity of gut microbes, and the balance between microorganisms and the host would be disrupted. This new state is defined as dysbiosis. It has been confirmed, in both clinical and experimental settings, that dysbiosis plays an important role in the occurrence and development of IBD, but the causal relationship between dysbiosis and inflammation has not been elucidated. On the other hand, as a classic research method for pathogen identification, the Koch's postulates sets the standard for verifying the role of pathogens in disease. With the further acknowledgment of the disease pathogenesis, it is realized that the traditional Koch's postulates is not applicable to the etiology research (determination) of infectious diseases. Thus, many researchers have carried out more comprehensive and complex elaboration of Koch's postulates to help people better understand and explain disease pathogenesis through the improved Koch's postulates. Therefore, focusing on the new perspective of the improved Koch's postulates is of great significance for deeply understanding the relationship between dysbiosis and IBD. This article has reviewed the studies on dysbiosis in IBD, the use of microbial agents in the treatment of IBD, and their relationship to the modified Koch's postulates.

Role of Probiotics in Human Health.

Certain bacteria, known as probiotics, have had a vastly beneficial effect on people's health; considering their benefits they have been mixed with a wide variety of foods for several decades now. The ability of probiotics to modify the immunological response of the host, antagonize pathogenic microbes, or compete for adhesion sites with pathogenic microorganisms is related to the action of probiotics against microorganisms. Infections of the digestive tract, irritable bowel, lactose intolerance, allergies, infections of the urogenital tract, cystic fibrosis, and various cancers can all be prevented and treated with the use of probiotics. They can reduce the side effects of various antibodies. In the field of oral health, dental caries, periodontal disease, and bad breath can be prevented and treated with the use of probiotics. The findings of several of these clinical studies indicate that probiotics may be beneficial in the treatment and prevention of various diseases and health issues. Validation of a significant number of these clinical investigations is necessary before the results can be applied to the clinical setting. Clinical studies play an important part in such investigations, and in the not-too-distant future, the outcomes of such trials will determine whether or not probiotics are effective in the treatment of disease. This article will attempt to provide a summary of the available literature on the benefits that these probiotics have with regard to health and disease. Probiotics are foods and/or supplements that contain non-pathogenic microbes such as bacteria and yeast that colonize the gut and can potentially yield a variety of health benefits. Research into the various ways in which probiotic bacteria could be used in the treatment of intestinal disorders is ongoing. Thanks to clinical studies and laboratory experiments, we now know more about how probiotics affect gut microbiome disorders. Studies can prove that probiotics can alleviate a variety of gastrointestinal ailments and improve overall health. This article concentrates on probiotics and commensal microbes, as well as their potential role in gut microbiome-related illnesses. In this section, we mark certain areas that need further work and studies so as to enhance our understanding of how probiotics help in the treatment and reduction of chances of gastrointestinal diseases.

Gut microbiota affects brain development and behavior.

The gut covers a large surface area of the body and faces various external factors. The brain works in concert with commensal microbes in the gut to efficiently process the enormous amount of chemical signals that enter the gut every day. This review discusses: (1) evidence that gut bacteria can alter brain development and behavior, (2) mechanisms by which gut bacteria communicate with the brain, (3) preclinical and clinical studies demonstrating the impact of gut microbiota on autism spectrum disorder, and (4) variables worth consideration by future research on gut bacteria.

Innovations in Therapeutic Improvement of the Cutaneous Microbiome in Children with Atopic Dermatitis

Biofilm is the dominant form of skin microbiota organization that provides adhesion and preservation of microorganisms in the skin micro-environment. It is necessary to ensure epidermal barrier function and local immunomodulation. Staphylococcus aureus becomes the major colonizer of skin lesions in case of atopic dermatitis exacerbation, and it also can form the biofilms. S. aureus growth and biofilm formation due to other microbial commensals on the skin of patients with atopic dermatitis leads to chronic output of pro-inflammatory cytokines and later to abnormalities in healthy skin microbiome. The role of microbial biofilm in human’s health makes the skin microbiota an attractive target for therapeutic intervention in various skin diseases.

Long COVID and the Neuroendocrinology of Microbial Translocation Outside the GI Tract: Some Treatment Strategies

Similar to previous pandemics, COVID-19 has been succeeded by well-documented post-infectious sequelae, including chronic fatigue, cough, shortness of breath, myalgia, and concentration difficulties, which may last 5 to 12 weeks or longer after the acute phase of illness. Both the psychological stress of SARS-CoV-2 infection and being diagnosed with COVID-19 can upregulate cortisol, a stress hormone that disrupts the efferocytosis effectors, macrophages, and natural killer cells, leading to the excessive accumulation of senescent cells and disruption of biological barriers. This has been well-established in cancer patients who often experience unrelenting fatigue as well as gut and blood–brain barrier dysfunction upon treatment with senescence-inducing radiation or chemotherapy. In our previous research from 2020 and 2021, we linked COVID-19 to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) via angiotensin II upregulation, premature endothelial senescence, intestinal barrier dysfunction, and microbial translocation from the gastrointestinal tract into the systemic circulation. In 2021 and 2022, these hypotheses were validated and SARS-CoV-2-induced cellular senescence as well as microbial translocation were documented in both acute SARS-CoV-2 infection, long COVID, and ME/CFS, connecting intestinal barrier dysfunction to disabling fatigue and specific infectious events. The purpose of this narrative review is to summarize what is currently known about host immune responses to translocated gut microbes and how these responses relate to fatiguing illnesses, including long COVID. To accomplish this goal, we examine the role of intestinal and blood–brain barriers in long COVID and other illnesses typified by chronic fatigue, with a special emphasis on commensal microbes functioning as viral reservoirs. Furthermore, we discuss the role of SARS-CoV-2/Mycoplasma coinfection in dysfunctional efferocytosis, emphasizing some potential novel treatment strategies, including the use of senotherapeutic drugs, HMGB1 inhibitors, Toll-like receptor 4 (TLR4) blockers, and membrane lipid replacement.

Metabolism and Colorectal Cancer.

Reprogrammed metabolism is a hallmark of colorectal cancer (CRC). CRC cells are geared toward rapid proliferation, requiring nutrients and the removal of cellular waste in nutrient-poor environments. Intestinal stem cells (ISCs), the primary cell of origin for CRCs, must adapt their metabolism along the adenoma-carcinoma sequence to the unique features of their complex microenvironment that include interactions with intestinal epithelial cells, immune cells, stromal cells, commensal microbes, and dietary components. Emerging evidence implicates modifiable risk factors related to the environment, such as diet, as important in CRC pathogenesis. Here, we focus on describing the metabolism of ISCs, diets that influence CRC initiation, CRC genetics and metabolism, and the tumor microenvironment. The mechanistic links between environmental factors, metabolic adaptations, and the tumor microenvironment in enhancing or supporting CRC tumorigenesis are becoming better understood. Thus, greater knowledge of CRC metabolism holds promise for improved prevention and treatment.

More than Meets the Eye: Untargeted Metabolomics and Lipidomics Reveal Complex Pathways Spurred by Activation of Acid Resistance Mechanisms in Escherichia coli.

Escherichia coli is a ubiquitous group of bacteria that can be either commensal gut microbes or enterohemorrhagic food-borne pathogens. Regardless, both forms must survive acidic environments in the stomach and intestines to reach and colonize the gut, a process that partially relies on amino acid-dependent acid resistance (AR) mechanisms and modifications to membrane phospholipids. However, only the basic tenets of these mechanisms have been elucidated. In this paper, we aim to conduct a full-scale metabolic and lipidomic characterization of E. coli's adaptations to acid stress. We hypothesized that the use of untargeted metabolomics and lipidomics would reveal mechanisms downstream of AR processes that provide novel contributions to acid stress survival. We detected significant differences in the extracellular metabolome and the lipidome induced by amino acid supplementation (glutamine, arginine, or lysine) and contextualized these results using real-time quantitative polymerase chain reaction (RT-qPCR). We additionally identified several metabolic pathways as well as a significant alteration in phospholipid synthetic pathways induced by differential amino acid supplementation. These results demonstrate that AR may extend beyond canonical mechanisms to a coordinated metabolic phenotype. Future studies may benefit from our analysis to further elucidate distinct targets for prebiotic supplements to cultivate commensal strains or therapies to combat pathogenic ones.

Probiotic Regulation to Modulate Aging Gut and Brain Health: A Concise Review

The human gastrointestinal (GI) tract contains a diverse mixture of commensal and pathogenic microbes, forming the gut microbiome. These gut microbes and their potential to improve human health are a topic of great interest to the scientific community. Many intestinal and age-related complications are linked to dysbiosis of the gut microbiome, often associated with a weakened immune system. A decrease in beneficial microbes, generally, along with decreased microbial diversity in the gut, can, in many cases, result in disease, particularly in older individuals. Probiotics, which are ingestible beneficial microorganisms, have the potential to positively modulate the indigenous gut microbiota. There are two predominant and conventional classes of lactic acid bacterial probiotics, lactobacilli and bifidobacteria, which have been confirmed for their health benefits and role in preventing certain gut-related disorders. The proper use of probiotics and/or supplements, along with a consistently healthy lifestyle, is a promising holistic approach to maintaining or improving gut health and minimizing other age-linked disorders. There are many properties that bacterial probiotics possess, which may allow for these beneficial effects in the gut. For instance, probiotics have adhesion capacities (capability to stay in GI tract) that are effective in excluding pathogens, while other probiotics have the potential to stimulate or modulate the intestinal immune system by regulating genes that reside within and outside of the gut environment. This review discussed the possible underlying mechanics of probiotics, evidence of probiotic-based mitigation of age-related disease, and the role of probiotics in modulating gut health and, in turn, maintaining brain health.