Review

Authors: Rebeca Martín, David Rios-Covian, Eugénie Huillet...

In humans, many diseases are associated with alterations in gut microbiota, namely increases or decreases in the abundance of specific bacterial groups. One example is the genus Faecalibacterium. Numerous studies have underscored that low levels of Faecalibacterium are correlated with inflammatory conditions, with inflammatory bowel disease (IBD) in the forefront. Its representation is also diminished in the case of several diseases, including colorectal cancer (CRC), dermatitis, and depression. Additionally, the relative presence of this genus is considered to reflect, at least in part, intestinal health status because Faecalibacterium is frequently present at reduced levels in individuals with gastrointestinal diseases or disorders. In this review, we first thoroughly describe updates to the taxonomy of Faecalibacterium, which has transformed a single-species taxon to a multispecies taxon over the last decade. We then explore the links discovered between Faecalibacterium abundance and various diseases since the first IBD-focused studies were published. Next, we examine current available strategies for modulating Faecalibacterium levels in the gut. Finally, we summarize the mechanisms underlying the beneficial effects that have been attributed to this genus. Together, epidemiological and experimental data strongly support the use of Faecalibacterium as a next-generation probiotic (NGP) or live biotherapeutic product (LBP).

Topics: Humans; Faecalibacterium; Inflammatory Bowel Diseases; Bacteria; Gastrointestinal Microbiome; Gastrointestinal Diseases

PubMed: 37451743
DOI: 10.1093/femsre/fuad039

Review

Authors: Raden Mohamad Rendy Ariezal Effendi, Muhammad Anshory, Handono Kalim...

Probiotics and synbiotics are used to treat chronic illnesses due to their roles in immune system modulation and anti-inflammatory response. They have been shown to reduce inflammation in a number of immune-related disorders, including systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and chronic inflammatory skin conditions such as psoriasis and atopic dermatitis (AD). () and () are two different types of bacteria that play a significant part in this function. It has been established that and are abundant in normal populations and have protective benefits on digestive health while also enhancing the immune system, metabolism, and gut barrier of the host. They have the potential to be a therapeutic target in diseases connected to the microbiota, such as immunological disorders and cancer immunotherapy. There has not been a review of the anti-inflammatory effects of and , particularly in immunological diseases. In this review, we highlight the most recent scientific findings regarding and as two significant gut microbiota for microbiome alterations and seek to provide cutting-edge insight in terms of microbiome-targeted therapies as promising preventive and therapeutic tools in immune-related diseases and cancer immunotherapy.

PubMed: 36557635
DOI: 10.3390/microorganisms10122382

Review

Authors: Omnia Momtaz Al-Fakhrany, Engy Elekhnawy

Recent and continuing advances in gut microbiome research have pointed out the role of the gut microbiota as an unexplored source of potentially beneficial probiotic microbes. Along the lines of these advances, both public awareness and acceptance of probiotics are increasing. That's why; academic and industrial research is dedicated to identifying and investigating new microbial strains for the development of next-generation probiotics (NGPs). At this time, there is a growing interest in NGPs as biotherapeutics that alter the gut microbiome and affect various diseases development. In this work, we have focused on some emergent and promising NGPs, specifically Eubacterium hallii, Faecalibacterium prausnitzii, Roseburia spp., Akkermansia muciniphila, and Bacteroides fragilis, as their presence in the gut can have an impact on the development of various diseases. Emerging studies point out the beneficial roles of these NGPs and open up novel promising therapeutic options. Interestingly, these NGPs were found to enhance gastrointestinal immunity, enhance immunotherapy efficacy in cancer patients, retain the intestinal barrier integrity, generate valuable metabolites, especially short-chain fatty acids, and decrease complications of chemotherapy and radiotherapy. Although many of these NGPs are considered promising for the prevention and treatment of several chronic diseases, research on humans is still lacking. Therefore, approval of these microbes from regulatory agencies is rare. Besides, some issues limit their wide use in the market, such as suitable methods for the culture and storage of these oxygen-sensitive microbes. The present review goes over the main points related to NGPs and gives a viewpoint on the key issues that still hinder their wide application. Furthermore, we have focused on the advancement in NGPs and human healthiness investigations by clarifying the limitations of traditional probiotic microorganisms, discussing the characteristics of emerging NGPs and defining their role in the management of certain ailments. Future research should emphasize the isolation, mechanisms of action of these probiotics, safety, and clinical efficacy in humans.

Topics: Humans; Gastrointestinal Microbiome; Immunotherapy; Oxygen; Probiotics

PubMed: 38619680
DOI: 10.1007/s11033-024-09398-5

Review

Authors: Bruno Bonnechère, Najaf Amin, Cornelia van Duijn...

There is a growing body of evidence highlighting there are significant changes in the gut microbiota composition and relative abundance in various neurological disorders. We performed a systematic review of the different microbiota altered in a wide range of neurological disorders (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis, and stroke). Fifty-two studies were included representing 5496 patients. At the genus level, the most frequently involved microbiota are Akkermansia, Faecalibacterium, and Prevotella. The overlap between the pathologies was strongest for MS and PD, sharing eight genera (Akkermansia, Butyricicoccus, Bifidobacterium, Coprococcus, Dorea, Faecalibacterium, Parabacteroides, and Prevotella) and PD and stroke, sharing six genera (Enterococcus, Faecalibacterium, Lactobacillus, Parabacteroides, Prevotella, and Roseburia). The identification signatures overlapping for AD, PD, and MS raise the question of whether these reflect a common etiology or rather common consequence of these diseases. The interpretation is hampered by the low number and low power for AD, ALS, and stroke with ample opportunity for false positive and false negative findings.

Topics: Humans; Gastrointestinal Microbiome; Nervous System Diseases; Parkinson Disease; Microbiota; Akkermansia; Multiple Sclerosis; Prevotella; Clostridiaceae; Clostridiales; Stroke

PubMed: 36430144
DOI: 10.3390/ijms232213665

Authors: Hong-Bao Li, Meng-Lu Xu, Xu-Dong Xu...

BACKGROUND

Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of in CKD are reported. However, the mechanisms about if and how can be used as a probiotic to treat CKD remains unknown.

METHODS

We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes.

RESULTS

We observed significant depletion of in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by -derived butyrate were through the GPR (G protein-coupled receptor)-43.

CONCLUSIONS

Using a mouse CKD model, we uncovered a novel beneficial role of in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of for ameliorating CKD.

Topics: Animals; Butyrates; Disease Models, Animal; Faecalibacterium prausnitzii; Inflammation; Kidney; Receptors, G-Protein-Coupled; Renal Insufficiency, Chronic

PubMed: 36164984
DOI: 10.1161/CIRCRESAHA.122.320184

Authors: Xia Chen, Pan Li, Mian Liu...

OBJECTIVE

Pre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown.

DESIGN

We performed a case-control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation.

RESULTS

Patients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly and , were enriched, whereas beneficial bacteria, including and , were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, , and inflammatory cytokine levels were significantly increased.

CONCLUSIONS

This study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.

Topics: Animals; Bacterial Translocation; Blood Pressure; CD4 Lymphocyte Count; Case-Control Studies; Chemokines; Creatinine; Cytokines; Disease Models, Animal; Dysbiosis; Faecalibacterium; Feces; Female; Fetal Resorption; Fusobacteria; Gastrointestinal Microbiome; Humans; Intestine, Small; Mice; Placenta; Pre-Eclampsia; Pregnancy; Proteinuria; RNA, Messenger; T-Lymphocytes, Regulatory; Th17 Cells; Veillonella

PubMed: 31900289
DOI: 10.1136/gutjnl-2019-319101

Authors: Juneyoung Lee, John d'Aigle, Louise Atadja...

RATIONALE

The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown.

OBJECTIVE

To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy.

METHODS AND RESULTS

Aged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers (, , , and ) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice.

CONCLUSIONS

This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.

Topics: Age Factors; Animals; Bifidobacterium longum; Brain Chemistry; Clostridium symbiosum; Faecalibacterium prausnitzii; Fatty Acids, Volatile; Fecal Microbiota Transplantation; Feces; Gastrointestinal Microbiome; Infarction, Middle Cerebral Artery; Interleukin-17; Intestines; Intraepithelial Lymphocytes; Ischemic Stroke; Limosilactobacillus fermentum; Male; Mice; Mucin-2; Mucin-4; T-Lymphocytes, Regulatory

PubMed: 32354259
DOI: 10.1161/CIRCRESAHA.119.316448

Authors: Jiye Cheng, Siddarth Venkatesh, Ke Ke...

Undernutrition in Bangladeshi children is associated with disruption of postnatal gut microbiota assembly; compared with standard therapy, a microbiota-directed complementary food (MDCF) substantially improved their ponderal and linear growth. Here, we characterize a fatty acid amide hydrolase (FAAH) from a growth-associated intestinal strain of cultured from these children. This enzyme, expressed and purified from hydrolyzes a variety of -acylamides, including oleoylethanolamide (OEA), neurotransmitters, and quorum sensing -acyl homoserine lactones; it also synthesizes a range of -acylamides, notably -acyl amino acids. Treating germ-free mice with -oleoylarginine and -oleolyhistidine, major products of FAAH OEA metabolism, markedly affected expression of intestinal immune function pathways. Administering MDCF to Bangladeshi children considerably reduced fecal OEA, a satiety factor whose levels were negatively correlated with abundance and expression of their FAAH. This enzyme, structurally and catalytically distinct from mammalian FAAH, is positioned to regulate levels of a variety of bioactive molecules.

Topics: Animals; Child, Preschool; Humans; Mice; Amidohydrolases; Bangladesh; Endocannabinoids; Escherichia coli; Faecalibacterium prausnitzii; Feces; Gastrointestinal Microbiome; Germ-Free Life; Hydrolysis; Oleic Acids; Quorum Sensing; Gastrointestinal Tract; Substrate Specificity

PubMed: 39446943
DOI: 10.1126/science.ado6828

Authors: Sònia Sánchez-Pérez, Oriol Comas-Basté, Adriana Duelo...

An underlying cause of histamine intolerance is diamine oxidase (DAO) deficiency, which leads to defective homeostasis and a higher systemic absorption of histamine. Impaired DAO activity may have a genetic, pharmacological or pathological origin. A recent proposal also suggests it can arise from an alteration in the gut microbiota, although only one study has explored this hypothesis to date. A greater abundance of histamine-secreting bacteria in the gut could lead to the development of histamine intolerance. Thus, the aim of this study was to characterize the composition of the intestinal microbiota of patients with histamine intolerance symptoms and compare it with that of healthy individuals. The study was performed by sequencing bacterial 16S rRNA genes (V3-V4 region) and analyzing the data using the EzBioCloud Database. Dysbiosis of the gut microbiota was observed in the histamine intolerance group who, in comparison with the healthy individuals, had a significantly lower proportion of , , and , which are bacteria related to gut health. They also had a significantly higher abundance of histamine-secreting bacteria, including the genera and , several unidentified genera belonging to the family and the species and . A greater abundance of histaminogenic bacteria would favor the accumulation of high levels of histamine in the gut, its subsequent absorption in plasma and the appearance of adverse effects, even in individuals without DAO deficiency.

Topics: Amine Oxidase (Copper-Containing); Bacteria; Dysbiosis; Faecalibacterium; Feces; Gastrointestinal Microbiome; Histamine; Humans; RNA, Ribosomal, 16S

PubMed: 35565742
DOI: 10.3390/nu14091774

Authors: Hai-Tao Yang, Zhi-Hui Jiang, Yi Yang...

BACKGROUND

The gut microbiota plays a crucial role in coronary artery disease (CAD) development, but limited attention has been given to the role of the microbiota in preventing this disease. This study aimed to identify key biomarkers using metagenomics and untargeted metabolomics and verify their associations with atherosclerosis.

METHODS

A total of 371 participants, including individuals with various CAD types and CAD-free controls, were enrolled. Subsequently, significant markers were identified in the stool samples through gut metagenomic sequencing and untargeted metabolomics. In vivo and in vitro experiments were performed to investigate the mechanisms underlying the association between these markers and atherosclerosis.

RESULTS

Faecal omics sequencing revealed that individuals with a substantial presence of Faecalibacterium prausnitzii had the lowest incidence of CAD across diverse CAD groups and control subjects. A random forest model confirmed the significant relationship between F. prausnitzii and CAD incidence. Notably, F. prausnitzii emerged as a robust, independent CAD predictor. Furthermore, our findings indicated the potential of the gut microbiota and gut metabolites to predict CAD occurrence and progression, potentially impacting amino acid and vitamin metabolism. F. prausnitzii mitigated inflammation and exhibited an antiatherosclerotic effect on ApoE mice after gavage. This effect was attributed to reduced intestinal LPS synthesis and reinforced mechanical and mucosal barriers, leading to decreased plasma LPS levels and an antiatherosclerotic outcome.

CONCLUSIONS

Sequencing of the samples revealed a previously unknown link between specific gut microbiota and atherosclerosis. Treatment with F. prausnitzii may help prevent CAD by inhibiting atherosclerosis.

Topics: Humans; Animals; Mice; Faecalibacterium prausnitzii; Lipopolysaccharides; Gastrointestinal Microbiome; Atherosclerosis

PubMed: 38243314
DOI: 10.1186/s12964-023-01464-y