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Inflammatory dysbiotic diseases present an intriguing biological paradox. Like most other infectious disease processes, the alarm bells of the host are potently activated by tissue-destructive pathobionts, triggering a cascade of physiological responses that ultimately mobilize immune cells like neutrophils to sites of active infection. Typically, these inflammatory host responses are critical to inhibit and/or eradicate infecting microbes. However, for many inflammatory dysbiotic diseases, inflammophilic pathobiont-enriched communities not only survive the inflammatory response, but they actually obtain a growth advantage when challenged with an inflammatory environment. This is especially true for those organisms that have evolved various strategies to resist and/or manipulate components of innate immunity. In contrast, members of the commensal microbiome typically experience a competitive growth disadvantage under inflammatory selective pressure, hindering their critical ability to restrict pathobiont proliferation. Here, we examine examples of bacteria-neutrophil interactions from both conventional pathogens and inflammophiles. We discuss some of the strategies utilized by them to illustrate how inflammophilic microbes can play a central role in the positive feedback cycle that exemplifies dysbiotic chronic inflammatory diseases.

Bacterial inhabitants of the body have the potential to play a role in various stages of cancer initiation, progression, and treatment. These bacteria may be distal to the primary tumour, such as gut microbiota, or local to the tissue, before or after tumour growth. Breast cancer is well studied in this context. Amongst breast cancer types, Triple Negative Breast Cancer (TNBC) is more aggressive, has fewer treatment options than receptor-positive breast cancers, has an overall worse prognosis and higher rates of reoccurrence. Thus, an indepth understanding of the bacterial influence on TNBC progression and treatment is of high value. In this regard, the Gut Microbiota (GM) can be involved in various stages of tumour progression. It may suppress or promote carcinogenesis through the release of carcinogenic metabolites, sustenance of proinflammatory environments and/or the promotion of epigenetic changes in our genome. It can also mediate metastasis and reoccurrence through interactions with the immune system and has been recently shown to influence chemo-, radio-, and immune-therapies. Furthermore, bacteria have also been found to reside in normal and malignant breast tissue. Several studies have now described the breast and breast tumour microbiome, with the tumour microbiota of TNBC having the least taxonomic diversity among all breast cancer types. Here, specific conditions of the tumour microenvironment (TME) - low O2, leaky vasculature and immune suppression - are supportive of tumour selective bacterial growth. This innate bacterial ability could enable their use as delivery agents for various therapeutics or as diagnostics. This review aims to examine the current knowledge on bacterial relevance to TNBC and potential uses while examining some of the remaining unanswered questions regarding mechanisms underpinning observed effects. [ABSTRACT FROM AUTHOR]

Bacterial inhabitants of the body have the potential to play a role in various stages of cancer initiation, progression, and treatment. These bacteria may be distal to the primary tumour, such as gut microbiota, or local to the tissue, before or after tumour growth. Breast cancer is well studied in this context. Amongst breast cancer types, Triple Negative Breast Cancer (TNBC) is more aggressive, has fewer treatment options than receptor-positive breast cancers, has an overall worse prognosis and higher rates of reoccurrence. Thus, an in-depth understanding of the bacterial influence on TNBC progression and treatment is of high value. In this regard, the Gut Microbiota (GM) can be involved in various stages of tumour progression. It may suppress or promote carcinogenesis through the release of carcinogenic metabolites, sustenance of proinflammatory environments and/or the promotion of epigenetic changes in our genome. It can also mediate metastasis and reoccurrence through interactions with the immune system and has been recently shown to influence chemo-, radio-, and immune-therapies. Furthermore, bacteria have also been found to reside in normal and malignant breast tissue. Several studies have now described the breast and breast tumour microbiome, with the tumour microbiota of TNBC having the least taxonomic diversity among all breast cancer types. Here, specific conditions of the tumour microenvironment (TME) - low O2, leaky vasculature and immune suppression - are supportive of tumour selective bacterial growth. This innate bacterial ability could enable their use as delivery agents for various therapeutics or as diagnostics. This review aims to examine the current knowledge on bacterial relevance to TNBC and potential uses while examining some of the remaining unanswered questions regarding mechanisms underpinning observed effects.

Contemporary asthma management requires a proactive and individualized approach, combining precision diagnosis and personalized treatment. The introduction of biologic therapies for severe asthma to everyday clinical practice, increases the need for specific patient selection, prediction of outcomes and monitoring of these costly and long-lasting therapies. Several biomarkers have been used in asthma in disease identification, prediction of asthma severity and prognosis, and response to treatment. Novel advances in the area of personalized medicine regarding disease phenotyping and endotyping, encompass the development and application of reliable biomarkers, accurately quantified using robust and reproducible methods. The availability of powerful omics technologies, together with integrated and network-based genome data analysis, and microbiota changes quantified in serum, body fluids and exhaled air, will lead to a better classification of distinct phenotypes or endotypes. Herein, in this review we discuss on currently used and novel biomarkers for the diagnosis and treatment of asthma.

Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1→3)-β-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and Escherichia spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14-CD16+) and NK cells (CD56+CD16-) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection. [ABSTRACT FROM AUTHOR]

New lines of evidence suggest that the oral-systemic medical links and oral hypo-function are progressively transcending beyond the traditional clinical signs and symptoms of oral diseases. Research into the dysbiotic microbiome, host immune/inflammatory regulations and patho-physiologic changes and subsequent adaptations through the oral-systemic measures under ageism points to pathways leading to mastication deficiency, dysphagia, signature brain activities for (neuro)-cognition circuitries, dementia and certain cancers of the digestive system as well. Therefore, the coming era of oral health-linked systemic disorders will likely reshape the future of diagnostics in oral geriatrics, treatment modalities and professional therapies in clinical disciplines. In parallel to these highlights, a recent international symposium was jointly held by the International Association of Gerontology and Geriatrics (IAGG), Japanese Society of Gerodontology (JSG), the representative of USA and Taiwan Academy of Geriatric Dentistry (TAGD) on Oct 25th, 2019. Herein, specific notes are briefly addressed and updated for a summative prospective from this symposium and the recent literature.

Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1→3)-β-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and Escherichia spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14-CD16+) and NK cells (CD56+CD16-) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection.

Oral cancer is a globally widespread cancer that features among the three most prevalent cancers in India. The risk of oral cancer is elevated by factors such as tobacco consumption, betel-quid chewing, excessive alcohol consumption, unhygienic oral condition, sustained viral infections, and also due to dysbiosis in microbiome composition of the oral cavity. Here, we performed an oral microbiome study of healthy and oral cancer patients to decipher the microbial dysbiosis due to the consumption of smokeless-tobacco-based products and also revealed the tobacco-associated microbiome. The analysis of 196 oral microbiome samples from three different oral sites of 32 healthy and 34 oral squamous cell carcinoma (OSCC) patients indicated health status, site of sampling, and smokeless tobacco consumption as significant covariates associated with oral microbiome composition. Significant similarity in oral microbiome composition of smokeless-tobacco-consuming healthy samples and OSCC samples inferred the possible role of smokeless tobacco consumption in increasing inflammation-associated species in oral microbiome. Significantly higher abundance of Streptococcus was found to adequately discriminate smokeless-tobacco-non-consuming healthy samples from smokeless-tobacco-consuming healthy samples and contralateral healthy site of OSCC samples from the tumor site of OSCC samples. Comparative analysis of oral microbiome from another OSCC cohort also confirmed Streptococcus as a potential marker for healthy oral microbiome. Gram-negative microbial genera such as Prevotella , Capnocytophaga , and Fusobacterium were found to be differentially abundant in OSCC-associated microbiomes and can be considered as potential microbiome marker genera for oral cancer. Association with lipopolysaccharide (LPS) biosynthesis pathway further confirms the differential abundance of Gram-negative marker genera in OSCC microbiomes. [ABSTRACT FROM AUTHOR]

Oral cancer is a globally widespread cancer that features among the three most prevalent cancers in India. The risk of oral cancer is elevated by factors such as tobacco consumption, betel-quid chewing, excessive alcohol consumption, unhygienic oral condition, sustained viral infections, and also due to dysbiosis in microbiome composition of the oral cavity. Here, we performed an oral microbiome study of healthy and oral cancer patients to decipher the microbial dysbiosis due to the consumption of smokeless-tobacco-based products and also revealed the tobacco-associated microbiome. The analysis of 196 oral microbiome samples from three different oral sites of 32 healthy and 34 oral squamous cell carcinoma (OSCC) patients indicated health status, site of sampling, and smokeless tobacco consumption as significant covariates associated with oral microbiome composition. Significant similarity in oral microbiome composition of smokeless-tobacco-consuming healthy samples and OSCC samples inferred the possible role of smokeless tobacco consumption in increasing inflammation-associated species in oral microbiome. Significantly higher abundance of Streptococcus was found to adequately discriminate smokeless-tobacco-non-consuming healthy samples from smokeless-tobacco-consuming healthy samples and contralateral healthy site of OSCC samples from the tumor site of OSCC samples. Comparative analysis of oral microbiome from another OSCC cohort also confirmed Streptococcus as a potential marker for healthy oral microbiome. Gram-negative microbial genera such as Prevotella, Capnocytophaga, and Fusobacterium were found to be differentially abundant in OSCC-associated microbiomes and can be considered as potential microbiome marker genera for oral cancer. Association with lipopolysaccharide (LPS) biosynthesis pathway further confirms the differential abundance of Gram-negative marker genera in OSCC microbiomes.

This article, titled "Editorial: The genetics and epigenetics of mental health," explores the interaction of genetic variants, epigenetic mechanisms, and environmental risk factors in mental health. The article summarizes seven relevant studies on the topic, covering areas such as stress, early-life experiences, obsessive-compulsive disorder, microbiomes, suicidal behavior, and psychogenic nonepileptic seizures. The studies reveal shared etiologies and pathophysiological pathways between mental health conditions and other disorders. However, the studies have limitations, such as small sample sizes and incomplete phenotype descriptions. The article concludes by posing important questions about the role of early-life epigenetic processes, the microbiome, and genetic variants in mental health, and the implications for public health measures. [Extracted from the article]

The vaginal microbiome plays a critical role in determining the progression of female genital tract infections; however, little is known about the vaginal microbiota of Indian women. We aimed to investigate the vaginal microbial architecture of women with asymptomatic bacterial vaginosis (BV) (n=20) and normal microbiota (n=19). Microbial diversity was analyzed in vaginal swabs from regularly menstruating women (18-45yrs) by 16S rRNA V3-V4 amplicon (MiSeq Illumina) sequencing. Rarefaction analysis showed a higher number of species in normal flora compared to BV. Alpha diversity as measured by Pielou’s evenness revealed microbial diversity was significantly greater in BV samples than normal microbiota (p= 0.0165). Beta diversity comparison using UniFrac metrics indicated distinct microbial communities clustering between normal and BV flora. Firmicutes were the major phyla observed in vaginal specimens of normal microbiota whereas Actinobacteria, Fusobacteria, Bacteroidetes were significantly abundant in BV samples. Notably, the relative abundance of Lactobacillus was significantly high in normal microbiota. Conversely Gardnerella, Sneathia, Prevotella, Atopobium, Ureaplasma, Dialister significantly dominated dysbiotic microbiota. Relative frequency of Lactobacillus decreased significantly in BV (6%) as compared to normal microbiota (35.2%). L. fermentum, L. gasseri, L. iners, L. jensenii, L. mucosae, L. ruminis, L. salivarius, L. coleohominis was more exclusively present in normal microbiota. L. iners was detected from both the groups with a relative frequency of 50.4% and 17.2% in normal and BV microbiota respectively. Lefse analysis indicated Atopobium vaginae, Sneathia amnii, Mycoplasma hominis Prevotella disiens in the vaginal microbiota as a biomarker for dysbiosis and L. jensenii as a biomarker of a healthy microbiota. Firmicutes were negatively correlated to Tenericutes, Actinobacteria, Bacteroidetes, and Fusobacteria. Proteobacteria positively correlated to Tenericutes, and Bacteroidetes were shown to be positively correlated to Fusobacteria. Predicted functional analysis indicated differences in the functional profiles between BV and normal microbiota. Normal microbiota utilized pathways essential for phosphatidylglycerol biosynthesis I & II, peptidoglycan biosynthesis, geranylgeranyl diphosphate biosynthesis I, mevalonate pathway, CoA biosynthesis pathway I and pyrimidine nucleotide salvage; whereas BV bacteria had characteristic aromatic amino acid biosynthesis, pentose phosphate pathway, carbohydrate degradation. In conclusion, women with asymptomatic BV have vaginal microbiota significantly different than women with normal microbiota. Furthermore, the study provides insights into the vaginal microbial structure of Indian women that will enable us to explore the prospective candidates for restoring the vaginal microbiota.

IntroductionShort chain fatty acids (SCFA) are gut microbiota-derived metabolites that contribute to the gut-brain axis and may impact stroke outcomes following gut dysbiosis. We evaluated plasma SCFA concentrations against stroke severity parameters and identified SCFA-associated protein networks.MethodsThe Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), a continuously enrolling tissue bank, was used to obtain stroke samples. Arterial blood distal and proximal to the thrombus was obtained from Acute Ischemic Stroke (AIS) Patients (n=53) during thrombectomy. Patient demographics, stroke presentation and outcome parameters were reported. The SCFAs were isolated from proximal plasma via chemical derivatization UHPLC coupled tandem mass spectrometry using electrospray ionization and multiple reaction monitoring. Proteomic levels for 184 cardioembolic and inflammatory proteins was quantified from systemic and intracranial plasma by Olink. Arterial blood from cerebrovascular patients undergoing elective neurointerventional procedures was used as controls.ResultsAcetate positively correlated with time from last known normal (LKN) and was significantly lower in stroke patients compared to control. Isobutyrate, Butyrate and 2-Methylbutyrate negatively correlated with %ΔNIHSS. Isobutyrate and 2-Methylbutyrate positively correlated with NIHSS discharge. SCFA concentrations were not associated with NIHSS admission, infarct volume, or edema volume. Multiple SCFAs positively associated with systemic and pro-inflammatory cytokines, most notably IL-6, TNF-α, VCAM1, IL-17, and MCP-1.ConclusionsPlasma SCFA concentrations taken at time of stroke are not associated with stroke severity at presentation. However, higher levels of SCFAs at the time of stroke are associated with increased markers of inflammation, less recovery from admission to discharge, and worse symptom burden at discharge.

The vaginal microbiome plays a critical role in determining the progression of female genital tract infections; however, little is known about the vaginal microbiota of Indian women. We aimed to investigate the vaginal microbial architecture of women with asymptomatic bacterial vaginosis (BV) (n=20) and normal microbiota (n=19). Microbial diversity was analyzed in vaginal swabs from regularly menstruating women (18-45yrs) by 16S rRNA V3-V4 amplicon (MiSeq Illumina) sequencing. Rarefaction analysis showed a higher number of species in normal flora compared to BV. Alpha diversity as measured by Pielou's evenness revealed microbial diversity was significantly greater in BV samples than normal microbiota (p= 0.0165). Beta diversity comparison using UniFrac metrics indicated distinct microbial communities clustering between normal and BV flora. Firmicutes were the major phyla observed in vaginal specimens of normal microbiota whereas Actinobacteria, Fusobacteria, Bacteroidetes were significantly abundant in BV samples. Notably, the relative abundance of Lactobacillus was significantly high in normal microbiota. Conversely Gardnerella , Sneathia , Prevotella , Atopobium , Ureaplasma , Dialister significantly dominated dysbiotic microbiota. Relative frequency of Lactobacillus decreased significantly in BV (6%) as compared to normal microbiota (35.2%). L. fermentum, L. gasseri, L. iners, L. jensenii, L. mucosae, L. ruminis, L. salivarius , L. coleohominis was more exclusively present in normal microbiota. L. iners was detected from both the groups with a relative frequency of 50.4% and 17.2% in normal and BV microbiota respectively. Lefse analysis indicated Atopobium vaginae, Sneathia amnii, Mycoplasma hominis Prevotella disiens in the vaginal microbiota as a biomarker for dysbiosis and L. jensenii as a biomarker of a healthy microbiota. Firmicutes were negatively correlated to Tenericutes, Actinobacteria, Bacteroidetes , and Fusobacteria. Proteobacteria positively correlated to Tenericute s, and Bacteroidetes were shown to be positively correlated to Fusobacteria. Predicted functional analysis indicated differences in the functional profiles between BV and normal microbiota. Normal microbiota utilized pathways essential for phosphatidylglycerol biosynthesis I & II, peptidoglycan biosynthesis, geranylgeranyl diphosphate biosynthesis I, mevalonate pathway, CoA biosynthesis pathway I and pyrimidine nucleotide salvage; whereas BV bacteria had characteristic aromatic amino acid biosynthesis, pentose phosphate pathway, carbohydrate degradation. In conclusion, women with asymptomatic BV have vaginal microbiota significantly different than women with normal microbiota. Furthermore, the study provides insights into the vaginal microbial structure of Indian women that will enable us to explore the prospective candidates for restoring the vaginal microbiota. [ABSTRACT FROM AUTHOR]

BackgroundAtopic dermatitis (AD) is characterized by an altered skin microbiome dominantly colonized by S. aureus. Standard treatment includes emollients, anti-inflammatory medications and antiseptics.ObjectivesTo characterize changes in the skin microbiome during treatment for AD.MethodsThe skin microbiomes of children with moderate-to-severe AD and healthy children were investigated in a longitudinal prospective study. Patients with AD were randomized to receive either standard treatment with emollients and topical corticosteroids or standard treatment with the addition of dilute bleach baths (DBB) and sampled at four visits over a three-month period. At each visit, severity of AD was measured, swabs were taken from four body sites and the composition of the microbiome at those sites was assessed using 16S rRNA amplification.ResultsWe included 14 healthy controls and 28 patients. We found high relative abundances of S. aureus in patients, which correlated with AD severity and reduced apparent alpha diversity. As disease severity improved with treatment, the abundance of S. aureus decreased, gradually becoming more similar to the microbiomes of healthy controls. After treatment, patients who received DBB had a significantly lower abundance of S. aureus than those who received only standard treatment.ConclusionsThere are clear differences in the skin microbiome of healthy controls and AD patients that diminish with treatment. After three months, the addition of DBB to standard treatment had significantly decreased the S. aureus burden, supporting its use as a therapeutic option. Further study in double-blinded trials is needed.

Background: Atopic dermatitis (AD) is characterized by an altered skin microbiome dominantly colonized by S. aureus. Standard treatment includes emollients, anti-inflammatory medications and antiseptics. Objectives: To characterize changes in the skin microbiome during treatment for AD. Methods: The skin microbiomes of children with moderate-to-severe AD and healthy children were investigated in a longitudinal prospective study. Patients with AD were randomized to receive either standard treatment with emollients and topical corticosteroids or standard treatment with the addition of dilute bleach baths (DBB) and sampled at four visits over a three-month period. At each visit, severity of AD was measured, swabs were taken from four body sites and the composition of the microbiome at those sites was assessed using 16S rRNA amplification. Results: We included 14 healthy controls and 28 patients. We found high relative abundances of S. aureus in patients, which correlated with AD severity and reduced apparent alpha diversity. As disease severity improved with treatment, the abundance of S. aureus decreased, gradually becoming more similar to the microbiomes of healthy controls. After treatment, patients who received DBB had a significantly lower abundance of S. aureus than those who received only standard treatment. Conclusions: There are clear differences in the skin microbiome of healthy controls and AD patients that diminish with treatment. After three months, the addition of DBB to standard treatment had significantly decreased the S. aureus burden, supporting its use as a therapeutic option. Further study in double-blinded trials is needed. [ABSTRACT FROM AUTHOR]

Tryptophan (Trp) is an essential amino acid primarily derived from the diet for use by the host for protein synthesis. The intestinal tract is lined with cells, both host and microbial, that uptake and metabolize Trp to also generate important signaling molecules. Serotonin (5-HT), kynurenine and its downstream metabolites, and to a lesser extent other neurotransmitters are generated by the host to signal onto host receptors and elicit physiological effects. 5-HT production by neurons in the CNS regulates sleep, mood, and appetite; 5-HT production in the intestinal tract by enterochromaffin cells regulates gastric motility and inflammation in the periphery. Kynurenine can signal onto the aryl hydrocarbon receptor (AHR) to elicit pleiotropic responses from several cell types including epithelial and immune cells, or can be further metabolized into bioactive molecules to influence neurodegenerative disease. There is a remarkable amount of cross-talk with the microbiome with regard to tryptophan metabolites as well. The gut microbiome can regulate the production of host tryptophan metabolites and can use dietary or recycled trp to generate bioactive metabolites themselves. Trp derivatives like indole are able to signal onto xenobiotic receptors, including AHR, to elicit tolerogenic effects. Here, we review studies that demonstrate that tryptophan represents a key intra-kingdom signaling molecule.

Tryptophan (Trp) is an essential amino acid primarily derived from the diet for use by the host for protein synthesis. The intestinal tract is lined with cells, both host and microbial, that uptake and metabolize Trp to also generate important signaling molecules. Serotonin (5-HT), kynurenine and its downstream metabolites, and to a lesser extent other neurotransmitters are generated by the host to signal onto host receptors and elicit physiological effects. 5-HT production by neurons in the CNS regulates sleep, mood, and appetite; 5-HT production in the intestinal tract by enterochromaffin cells regulates gastric motility and inflammation in the periphery. Kynurenine can signal onto the aryl hydrocarbon receptor (AHR) to elicit pleiotropic responses from several cell types including epithelial and immune cells, or can be further metabolized into bioactive molecules to influence neurodegenerative disease. There is a remarkable amount of cross-talk with the microbiome with regard to tryptophan metabolites as well. The gut microbiome can regulate the production of host tryptophan metabolites and can use dietary or recycled trp to generate bioactive metabolites themselves. Trp derivatives like indole are able to signal onto xenobiotic receptors, including AHR, to elicit tolerogenic effects. Here, we review studies that demonstrate that tryptophan represents a key intra-kingdom signaling molecule. [ABSTRACT FROM AUTHOR]

New lines of evidence suggest that the oral-systemic medical links and oral hypo-function are progressively transcending beyond the traditional clinical signs and symptoms of oral diseases. Research into the dysbiotic microbiome, host immune/inflammatory regulations and patho-physiologic changes and subsequent adaptations through the oral-systemic measures under ageism points to pathways leading to mastication deficiency, dysphagia, signature brain activities for (neuro)-cognition circuitries, dementia and certain cancers of the digestive system as well. Therefore, the coming era of oral health-linked systemic disorders will likely reshape the future of diagnostics in oral geriatrics, treatment modalities and professional therapies in clinical disciplines. In parallel to these highlights, a recent international symposium was jointly held by the International Association of Gerontology and Geriatrics (IAGG), Japanese Society of Gerodontology (JSG), the representative of USA and Taiwan Academy of Geriatric Dentistry (TAGD) on Oct 25th, 2019. Herein, specific notes are briefly addressed and updated for a summative prospective from this symposium and the recent literature. [ABSTRACT FROM AUTHOR]

Inflammatory dysbiotic diseases present an intriguing biological paradox. Like most other infectious disease processes, the alarm bells of the host are potently activated by tissue-destructive pathobionts, triggering a cascade of physiological responses that ultimately mobilize immune cells like neutrophils to sites of active infection. Typically, these inflammatory host responses are critical to inhibit and/or eradicate infecting microbes. However, for many inflammatory dysbiotic diseases, inflammophilic pathobiont-enriched communities not only survive the inflammatory response, but they actually obtain a growth advantage when challenged with an inflammatory environment. This is especially true for those organisms that have evolved various strategies to resist and/or manipulate components of innate immunity. In contrast, members of the commensal microbiome typically experience a competitive growth disadvantage under inflammatory selective pressure, hindering their critical ability to restrict pathobiont proliferation. Here, we examine examples of bacteria-neutrophil interactions from both conventional pathogens and inflammophiles. We discuss some of the strategies utilized by them to illustrate how inflammophilic microbes can play a central role in the positive feedback cycle that exemplifies dysbiotic chronic inflammatory diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Higashi, Qin, Borland, Kreth and Merritt.)

Bacterial inhabitants of the body have the potential to play a role in various stages of cancer initiation, progression, and treatment. These bacteria may be distal to the primary tumour, such as gut microbiota, or local to the tissue, before or after tumour growth. Breast cancer is well studied in this context. Amongst breast cancer types, Triple Negative Breast Cancer (TNBC) is more aggressive, has fewer treatment options than receptor-positive breast cancers, has an overall worse prognosis and higher rates of reoccurrence. Thus, an in-depth understanding of the bacterial influence on TNBC progression and treatment is of high value. In this regard, the Gut Microbiota (GM) can be involved in various stages of tumour progression. It may suppress or promote carcinogenesis through the release of carcinogenic metabolites, sustenance of proinflammatory environments and/or the promotion of epigenetic changes in our genome. It can also mediate metastasis and reoccurrence through interactions with the immune system and has been recently shown to influence chemo-, radio-, and immune-therapies. Furthermore, bacteria have also been found to reside in normal and malignant breast tissue. Several studies have now described the breast and breast tumour microbiome, with the tumour microbiota of TNBC having the least taxonomic diversity among all breast cancer types. Here, specific conditions of the tumour microenvironment (TME) - low O2, leaky vasculature and immune suppression - are supportive of tumour selective bacterial growth. This innate bacterial ability could enable their use as delivery agents for various therapeutics or as diagnostics. This review aims to examine the current knowledge on bacterial relevance to TNBC and potential uses while examining some of the remaining unanswered questions regarding mechanisms underpinning observed effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Devoy, Flores Bueso and Tangney.)

Contemporary asthma management requires a proactive and individualized approach, combining precision diagnosis and personalized treatment. The introduction of biologic therapies for severe asthma to everyday clinical practice, increases the need for specific patient selection, prediction of outcomes and monitoring of these costly and long-lasting therapies. Several biomarkers have been used in asthma in disease identification, prediction of asthma severity and prognosis, and response to treatment. Novel advances in the area of personalized medicine regarding disease phenotyping and endotyping, encompass the development and application of reliable biomarkers, accurately quantified using robust and reproducible methods. The availability of powerful omics technologies, together with integrated and network-based genome data analysis, and microbiota changes quantified in serum, body fluids and exhaled air, will lead to a better classification of distinct phenotypes or endotypes. Herein, in this review we discuss on currently used and novel biomarkers for the diagnosis and treatment of asthma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fouka, Domvri, Gkakou, Alevizaki, Steiropoulos, Papakosta and Porpodis.)

Autoimmune cholestatic liver disease includes both Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC). Both conditions result in impairment of hepatic bile flow ultimately leading to chronic liver injury, liver fibrosis and eventually end stage cirrhosis. Early and accurate diagnosis are important for the risk stratification, follow up and management of these patients. The underlying pathogenesis of these conditions have not been completely resolved and poses a barrier for the development of new diagnostic and prognostics tools. Current research work suggests that the pathogenesis of autoimmune cholestatic liver disease results from environmental, genetic, and a large component of underlying immune dysfunction. While the current available serum biomarkers and imaging modalities showcases progression in precision medicine for the management of autoimmune cholestatic liver disease, development of new biomarkers are still an area of need in this field. In this review, we will discuss the current and emerging biomarkers in patients with PBC, PSC, and a special population that exhibit overlap syndrome with autoimmune hepatitis (AIH). The use of these biomarkers for diagnosis and prognosis of these patients will be reviewed through the lens of the current understanding of the complex immune pathophysiology of these conditions., Competing Interests: MJF is the Medical Director of Mitogen Diagnostics Corporation and has received honoraria and consulting fees from Werfen International, Aesku Diagnostics GmbH and Alexion Canada. MGS is a member of advisory boards for Gilead, Intercept and Roche, has served as a speaker for Gilead, Intercept and Abbott and receives clinical trial research support from Gilead, BMS, CymaBay, Intercept, Genfit, Pfizer, Novartis, Astra Zeneca, GSK, Celgene, Novo Nordisk, Axcella Health Inc., Merck, Galectin Therapeutics. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nguyen, Fritzler and Swain.)

Introduction: Short chain fatty acids (SCFA) are gut microbiota-derived metabolites that contribute to the gut-brain axis and may impact stroke outcomes following gut dysbiosis. We evaluated plasma SCFA concentrations against stroke severity parameters and identified SCFA-associated protein networks., Methods: The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), a continuously enrolling tissue bank, was used to obtain stroke samples. Arterial blood distal and proximal to the thrombus was obtained from Acute Ischemic Stroke (AIS) Patients (n=53) during thrombectomy. Patient demographics, stroke presentation and outcome parameters were reported. The SCFAs were isolated from proximal plasma via chemical derivatization UHPLC coupled tandem mass spectrometry using electrospray ionization and multiple reaction monitoring. Proteomic levels for 184 cardioembolic and inflammatory proteins was quantified from systemic and intracranial plasma by Olink. Arterial blood from cerebrovascular patients undergoing elective neurointerventional procedures was used as controls., Results: Acetate positively correlated with time from last known normal (LKN) and was significantly lower in stroke patients compared to control. Isobutyrate, Butyrate and 2-Methylbutyrate negatively correlated with %ΔNIHSS. Isobutyrate and 2-Methylbutyrate positively correlated with NIHSS discharge. SCFA concentrations were not associated with NIHSS admission, infarct volume, or edema volume. Multiple SCFAs positively associated with systemic and pro-inflammatory cytokines, most notably IL-6, TNF-α, VCAM1, IL-17, and MCP-1., Conclusions: Plasma SCFA concentrations taken at time of stroke are not associated with stroke severity at presentation. However, higher levels of SCFAs at the time of stroke are associated with increased markers of inflammation, less recovery from admission to discharge, and worse symptom burden at discharge., Competing Interests: KP, JFF, and AS are cofounders of Cerelux, LLC. JC is employed by Dicerna Pharmaceuticals Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Henry, Frank, McLouth, Trout, Morris, Chen, Stowe, Fraser and Pennypacker.)