Reevaluating the hype: four bacterial metabolites under scrutiny

Fröhlich, Esther E.; Mayerhofer, Raphaela; Holzer, Peter

doi:10.1556/eujmi-d-14-00030

Cited by 5 publications

(4 citation statements)

References 178 publications

(136 reference statements)

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“…Nevertheless, colorectal carcinoma cells such as HT29 release IL-23 40 . Flagellin has attracted pharmacological interest to develop vaccines 41 and because its capability to stimulate immune responses 42 . Thus, we hypothesized the existence of additional protection against gut-infecting bacteria and pathogens in vegans and vegetarians.…”

Section: Discussionmentioning

confidence: 99%

Diet influences the functions of the human intestinal microbiome

Angelis

Ferrocino

Calabrese

et al. 2020

Sci Rep

139

103

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Gut microbes programme their metabolism to suit intestinal conditions and convert dietary components into a panel of small molecules that ultimately affect host physiology. To unveil what is behind the effects of key dietary components on microbial functions and the way they modulate host-microbe interaction, we used for the first time a multi-omic approach that goes behind the mere gut phylogenetic composition and provides an overall picture of the functional repertoire in 27 fecal samples from omnivorous, vegan and vegetarian volunteers. Based on our data, vegan and vegetarian diets were associated to the highest abundance of microbial genes/proteins responsible for cell motility, carbohydrate-and protein-hydrolyzing enzymes, transport systems and the synthesis of essential amino acids and vitamins. A positive correlation was observed when intake of fiber and the relative fecal abundance of flagellin were compared. Microbial cells and flagellin extracted from fecal samples of 61 healthy donors modulated the viability of the human (HT29) colon carcinoma cells and the host response through the stimulation of the expression of Toll-like receptor 5, lectin RegIIIα and three interleukins (IL-8, IL-22 and IL-23). Our findings concretize a further and relevant milestone on how the diet may prevent/mitigate disease risk. Comprising 10 12-14 cells from 100-1000 species, the human intestinal microbiome is a complex entity living in our body. It affects human health, sustenance and well-being 1. Functioning as an extra organ 2 , the intestinal microbiome uses nutrients from ingested foods, releases harmful or beneficial metabolites and regulates the immune system 3,4. Dysbiosis of the intestinal microbiome has been associated to various gastrointestinal (GI) and non-GI diseases, such as obesity, heart-, kidney-and liver-related diseases, cancer and autism 5-7 , but the dilemma whether it acts as cause or consequence remains too far from the solution. Because the simple phylogenetic characterization does not provide deep information on functional repertoires 8,9 , a number of projects and studies have employed the whole-community shotgun sequencing to combine the composition and gene content of the human intestinal microbiome 2,10. Current meta-genomic data show limited differences among individuals, which hypothesize the existence of a stable core microbiome and similar metabolic traits 10. Notwithstanding the relevance of these findings, they do not necessarily imply similar in vivo microbial activities. Indeed, a panel of factors (e.g., diet, host genetics and pharmacological treatments) markedly affect such activities 11. Dietary components have the capability to modulate the composition and mainly the function of the intestinal microbiome 3,12,13. Correlations between entero-gradients/types and vegetable-rich (Prevotella and Lachnospira) or animal protein-rich diets (Bacteroides and Clostridia/Ruminococcus) have been already highlighted 12,14 , but the impact of dietary components still remains unclear. Previously, we...

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Section: Discussionmentioning

confidence: 99%

Diet influences the functions of the human intestinal microbiome

Angelis

Ferrocino

Calabrese

et al. 2020

Sci Rep

139

103

View full text Add to dashboard Cite

show abstract

“…Flagellin is the primary component of bacterial flagella. This protein has the potential to bind to Toll-like receptor 5 (TLR5) activating the transcription nuclear factor-κβ (NF-κβ) signaling-pathway with inflammatory and anti-apoptotic outcomes [ 115 , 116 ]. Additionally, we found that acetaldehyde dehydrogenase and acetyl-CoA synthetase involved in glycolysis/gluconeogenesis were overrepresented in CRC samples.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiome of Moroccan colorectal cancer patients

Allali

Benkeblia

Bouguenouch

et al. 2018

Med Microbiol Immunol

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Although colorectal cancer is the third leading cause of death in Morocco, there are no studies of the microbiome changes associated with the disease in the Moroccan population. The aim of our study was to compare the stool microbiome of Moroccan cancer patients with healthy individuals. We analyzed the microbiome composition of samples from 11 CRC patients and 12 healthy individuals by 16S rRNA amplicon sequencing. Principal coordinate analysis of samples revealed defined cancer versus healthy clusters. Our findings showed that cancer samples had higher proportions of Firmicutes (T = 50.5%; N = 28.4%; p = 0.04), specifically of Clostridia (T = 48.3%; N = 19.0%; p = 0.002), and Fusobacteria (T = 0.1%; N = 0.0%; p = 0.02), especially of Fusobacteriia (T = 0.1%; N = 0.0%; p = 0.02), while Bacteroidetes were enriched in healthy samples (T = 35.1%; N = 62.8%; p = 0.06), particularly the class Bacteroidia (T = 35.1%; N = 62.6%; p = 0.06). Porphyromonas, Clostridium, Ruminococcus, Selenomonas, and Fusobacterium were significantly overrepresented in diseased patients, similarly to other studies. Predicted functional information showed that bacterial motility proteins, flagellar assembly, and fatty acid biosynthesis metabolism were significantly overrepresented in cancer patients, while amino acid metabolism and glycan biosynthesis were overrepresented in controls. This suggests that involvement of these functional metagenomes is similar and relevant in the carcinogenesis process, independent of the origin of the samples. Results from this study allowed identification of bacterial taxa relevant to the Moroccan population and encourages larger studies to facilitate population-directed therapeutic approaches.Electronic supplementary materialThe online version of this article (10.1007/s00430-018-0542-5) contains supplementary material, which is available to authorized users.

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“…Serum detection of specific microbes by testing for pathogen‐associated molecular patterns has proven insightful in GI disorders (Fukui, 2016; Sitaraman et al., 2005; Ziegler et al., 2008); however, high false‐positive rates do occur in LPS detection (Vancamelbeke & Vermeire, 2017). Alternatively, endogenous immune responses to microbes can be tested (Fröhlich et al., 2015; Fukui, 2016; Stevens et al., 2018), indicating immune activation secondary to microbial translocation (Landmann et al., 1996). However, some proteins, such as CD14 can be released by immune cells via non‐LPS dependent mechanisms.…”

Section: Future Directionsmentioning

confidence: 99%

Inflammation‐driven brain and gut barrier dysfunction in stress and mood disorders

Doney

Cadoret

Dion‐Albert

et al. 2021

Eur J of Neuroscience

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Regulation of emotions is generally associated exclusively with the brain. However, there is evidence that peripheral systems are also involved in mood, stress vulnerability vs. resilience, and emotion‐related memory encoding. Prevalence of stress and mood disorders such as major depression, bipolar disorder, and post‐traumatic stress disorder is increasing in our modern societies. Unfortunately, 30%–50% of individuals respond poorly to currently available treatments highlighting the need to further investigate emotion‐related biology to gain mechanistic insights that could lead to innovative therapies. Here, we provide an overview of inflammation‐related mechanisms involved in mood regulation and stress responses discovered using animal models. If clinical studies are available, we discuss translational value of these findings including limitations. Neuroimmune mechanisms of depression and maladaptive stress responses have been receiving increasing attention, and thus, the first part is centered on inflammation and dysregulation of brain and circulating cytokines in stress and mood disorders. Next, recent studies supporting a role for inflammation‐driven leakiness of the blood–brain and gut barriers in emotion regulation and mood are highlighted. Stress‐induced exacerbated inflammation fragilizes these barriers which become hyperpermeable through loss of integrity and altered biology. At the gut level, this could be associated with dysbiosis, an imbalance in microbial communities, and alteration of the gut–brain axis which is central to production of mood‐related neurotransmitter serotonin. Novel therapeutic approaches such as anti‐inflammatory drugs, the fast‐acting antidepressant ketamine, and probiotics could directly act on the mechanisms described here improving mood disorder‐associated symptomatology. Discovery of biomarkers has been a challenging quest in psychiatry, and we end by listing promising targets worth further investigation.

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Reevaluating the hype: four bacterial metabolites under scrutiny

Cited by 5 publications

References 178 publications

Diet influences the functions of the human intestinal microbiome

Diet influences the functions of the human intestinal microbiome

Gut microbiome of Moroccan colorectal cancer patients

Inflammation‐driven brain and gut barrier dysfunction in stress and mood disorders

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