Intestinal Inflammation in Children with Cystic Fibrosis Is Associated with Crohn’s-Like Microbiota Disturbances

Cystic fibrosis (CF) is a systemic genetic disease that leads to pulmonary and digestive disorders. In the majority of CF patients, the intestine is the site of chronic inflammation and microbiota disturbances. The link between gut inflammation and microbiota dysbiosis is still poorly understood. The main objective of this study was to assess gut microbiota composition in CF children depending on their intestinal inflammation. We collected fecal samples from 20 children with CF. Fecal calprotectin levels were measured and fecal microbiota was analyzed by 16S rRNA sequencing. We observed intestinal inflammation was associated with microbiota disturbances characterized mainly by increased abundances of Staphylococcus, Streptococcus, and Veillonella dispar, along with decreased abundances of Bacteroides, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii. Those changes exhibited similarities with that of Crohn’s disease (CD), as evidenced by the elevated CD Microbial-Dysbiosis index that we applied for the first time in CF. Furthermore, the significant over-representation of Streptococcus in children with intestinal inflammation appears to be specific to CF and raises the issue of gut–lung axis involvement. Taken together, our results provide new arguments to link gut microbiota and intestinal inflammation in CF and suggest the key role of the gut–lung axis in the CF evolution.

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Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition

Cells ◽

10.3390/cells8060517 ◽

2019 ◽

Vol 8 (6) ◽

pp. 517 ◽

Cited By ~ 12

Author(s):

Claudia Burrello ◽

Maria Rita Giuffrè ◽

Angeli Dominique Macandog ◽

Angelica Diaz-Basabe ◽

Fulvia Milena Cribiù ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Immune Cells ◽

Intestinal Inflammation ◽

Fecal Microbiota Transplantation ◽

Experimental Colitis ◽

Fecal Microbiota ◽

Microbiota Composition ◽

Chronic Intestinal Inflammation ◽

Gut Microbiota Composition

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

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Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide

Gut ◽

10.1136/gutjnl-2020-322599 ◽

2021 ◽

pp. gutjnl-2020-322599

Author(s):

Hsin-Chih Lai ◽

Tzu-Lung Lin ◽

Ting-Wen Chen ◽

Yu-Lun Kuo ◽

Chih-Jung Chang ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Inflammation ◽

Chronic Obstructive ◽

Microbiota Composition ◽

Active Components ◽

Toll Like Receptor 4 ◽

Obstructive Pulmonary Disease ◽

Anti Inflammatory ◽

Gut Microbiota Composition

ObjectiveChronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.DesignA murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.ResultsGut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.ConclusionThe gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.

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Susceptibility to Campylobacter Infection Is Associated with the Species Composition of the Human Fecal Microbiota

mBio ◽

10.1128/mbio.01212-14 ◽

2014 ◽

Vol 5 (5) ◽

Cited By ~ 40

Author(s):

Johan Dicksved ◽

Patrik Ellström ◽

Lars Engstrand ◽

Hilpi Rautelin

Keyword(s):

Gut Microbiota ◽

Mouse Models ◽

Fecal Microbiota ◽

Microbiota Composition ◽

Content Type ◽

Culture Positive ◽

Abattoir Workers ◽

Gut Microbiota Composition

ABSTRACTThe gut microbiota is essential for human health, but very little is known about how the composition of this ecosystem can influence and respond to bacterial infections. Here we address this by prospectively studying the gut microbiota composition before, during, and after naturalCampylobacterinfection in exposed poultry abattoir workers. The gut microbiota composition was analyzed with 16S amplicon sequencing of fecal samples from poultry abattoir workers during the peak season ofCampylobacterinfection in Sweden. The gut microbiota compositions were compared between individuals who became culture positive forCampylobacterand those who remained negative. Individuals who becameCampylobacterpositive had a significantly higher abundance ofBacteroides(P= 0.007) andEscherichia(P= 0.002) species than those who remained culture negative. Furthermore, this group had a significantly higher abundance ofPhascolarctobacterium(P= 0.017) andStreptococcus(P= 0.034) sequences than theCampylobacter-negative group, which had an overrepresentation ofClostridiales(P= 0.017), unclassifiedLachnospiraceae(P= 0.008), andAnaerovorax(P= 0.015) sequences. Intraindividual comparisons of the fecal microbiota compositions yielded small differences over time inCampylobacter-negative participants, but significant long-term changes were found in theCampylobacter-positive group (P< 0.005). The results suggest that the abundance of specific genera in the microbiota reduces resistance toCampylobactercolonization in humans and thatCampylobacterinfection can have long-term effects on the composition of the human fecal microbiota.IMPORTANCEStudies using mouse models have made important contributions to our understanding of the role of the gut microbiota in resistance to bacterial enteropathogen colonization. The relative abundances ofEscherichia coliandBacteroidesspecies have been pointed out as important determinants of susceptibility to Gram-negative pathogens in general andCampylobacterinfection in particular. In this study, we assessed the role of the human gut microbiota in resistance toCampylobactercolonization by studying abattoir workers that are heavily exposed to these bacteria. Individuals with a certain composition of the gut microbiota became culture positive forCampylobacter. As their microbiotas were characterized by high abundances ofBacteroidesspp. andE. coli, well in line with the findings with mouse models, these bacterial species likely play an important role in colonization resistance also in humans.

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A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders

European Psychiatry ◽

10.1192/j.eurpsy.2020.109 ◽

2020 ◽

Vol 64 (1) ◽

Author(s):

Elvira Anna Carbone ◽

Pasquale D'Amato ◽

Giuseppe Vicchio ◽

Pasquale De Fazio ◽

Cristina Segura-Garcia

Keyword(s):

Systematic Review ◽

Eating Disorders ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Fecal Microbiota Transplantation ◽

Alpha Diversity ◽

Fecal Microbiota ◽

Cochrane Library ◽

Affective Symptoms

Abstract Background There is growing interest in new factors contributing to the genesis of eating disorders (EDs). Research recently focused on the study of microbiota. Dysbiosis, associated with a specific genetic susceptibility, may contribute to the development of anorexia nervosa (AN), bulimia nervosa, or binge eating disorder, and several putative mechanisms have already been identified. Diet seems to have an impact not only on modification of the gut microbiota, facilitating dysbiosis, but also on its recovery in patients with EDs. Methods This systematic review based on the PICO strategy searching into PubMed, EMBASE, PsychINFO, and Cochrane Library examined the literature on the role of altered microbiota in the pathogenesis and treatment of EDs. Results Sixteen studies were included, mostly regarding AN. Alpha diversity and short-chain fatty acid (SCFA) levels were lower in patients with AN, and affective symptoms and ED psychopathology seem related to changes in gut microbiota. Microbiota-derived proteins stimulated the autoimmune system, altering neuroendocrine control of mood and satiety in EDs. Microbial richness increased in AN after weight regain on fecal microbiota transplantation. Conclusions Microbiota homeostasis seems essential for a healthy communication network between gut and brain. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of EDs. A restored microbial balance may be a possible treatment target for EDs. A better and more in-depth characterization of gut microbiota and gut–brain crosstalk is required. Future studies may deepen the therapeutic and preventive role of microbiota in EDs.

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A209 ROLE OF SEROTONIN-AUTOPHAGY AXIS IN REGULATION OF EPITHELIAL CELL FUNCTION AND MICROBIOTA COMPOSITION IN GUT

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.208 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 81-82

Author(s):

S Haq ◽

H Wang ◽

J J Kim ◽

E Y Kwon ◽

S Banskota ◽

...

Keyword(s):

Gut Microbiota ◽

Inflammatory Cytokines ◽

Intestinal Inflammation ◽

Microbiota Composition ◽

Ec Cells ◽

Mucosal Scraping ◽

Ht 29 ◽

Gut Microbiota Composition ◽

Pro Inflammatory Cytokines

Abstract Background Serotonin (5-hydroxytryptamine; 5-HT), an enteric signalling molecule mainly produced by the enterochromaffin (EC) cells of the intestinal epithelium regulates various processes of the gut. Tryptophan hydroxylase 1 (Tph1) is the rate-limiting enzyme of 5-HT biosynthesis in EC cells. In inflammatory bowel disease (IBD) and experimental colitis, there are alterations in 5-HT content and microbiota composition in the gut. Previously we reported, Tph1-deficient (Tph1-/-) mice with reduced 5-HT in the gut exhibit reduced susceptibility to colitis. The mechanism by which 5-HT regulates colitis is unknown. Autophagy, a catabolic process regulates the function of intestinal epithelial cells (IECs), gut microbiota, and protects against intestinal inflammation. Both aberrant 5-HT signalling and autophagy is implicated in colitis. It is unclear whether they interact in regulation of production of pro-inflammatory cytokines from IECs and gut microbiota composition in relation to colitis. Our hypothesis is, an increase in 5-HT signalling inhibits autophagy in the IECs, which results in up-regulation of colitis by increasing the production of pro-inflammatory cytokines, and by selection for a more colitogenic microbiota. Aims To define the role of 5-HT-autophagy axis in the production of pro-inflammatory cytokines from IECs and gut microbiota composition in intestinal inflammation. Methods We investigated level of autophagy with or without 5% dextran sodium sulphate (DSS) in colons, mucosal scraping and IECs of Tph1-/- and their wild-type (WT) littermates. In addition, autophagy and proinflammatory cytokine production were investigated in human colonic epithelial cells (HT-29) following stimulation by 5-HT. We evaluated colitis and gut microbiota composition in WT, Tph1-/-, epithelial-specific autophagy gene Atg7 deficient (Atg7ΔIEC), and Atg7ΔIECTph1-/- (double knock out; DKO) mice. Results Tph1 -/- mice, with less 5-HT in the gut than WT mice following DSS administration exhibited an up-regulation of autophagy markers in the colon, mucosal scraping and IECs along with reduction of colitis severity. 5-HT treatment of HT-29 cells resulted in down-regulation of autophagy and upregulation of pro-inflammatory cytokine, IL-8. DKO mice exhibited increased severity of DSS-colitis, and altered microbiota composition compared to Tph1-/- mice. Conclusions These findings suggest, an increase in 5-HT in colitis inhibits autophagy in the IECs that contribute to alteration of the gut microbiota and disease severity. Blocking 5-HT signalling may promote autophagy in the IECs and alleviate the severity of colitis. Understanding the contribution of 5-HT in autophagy may identify new therapeutic target in IBD and other intestinal inflammatory conditions that exhibit dysregulated autophagy. Funding Agencies CAG, CIHR

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Children Developing Celiac Disease Have a Distinct and Proinflammatory Gut Microbiota in the First 5 Years of Life

10.1101/2020.02.29.971242 ◽

2020 ◽

Cited By ~ 1

Author(s):

Qian Huang ◽

Yi Yang ◽

Vladimir Tolstikov ◽

Michael A. Kiebish ◽

Jonas F Ludvigsson ◽

...

Keyword(s):

Celiac Disease ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Plasma Metabolites ◽

List Type ◽

Healthy Controls ◽

Microbiota Composition ◽

Immune Mediated ◽

Gut Microbiota Composition

ABSTRACTObjectiveCeliac disease (CD) is an immune-mediated disease characterized by small intestinal inflammation. CD is associated with HLA-DQ2 and HLA-DQ8 haplotypes, however, genetics alone cannot explain the increasing incidence rates. The main goal of this study was to determine the role of the gut microbiota in CD pathogenesis in the first five years of life.DesignWe conducted a longitudinal study focusing on three developmental phases of the gut microbiota (ages 1, 2.5 and 5 years). The fecal samples were obtained from 16 children who developed CD and 16 matched controls. We used 16S sequencing combined with functional analysis, flow cytometry, immunoglobulin A (IgA) sequencing (IgA-seq), and plasma metabolomics to determine a microbial link to CD pathogenesis.ResultsWe identified a distinct gut microbiota composition in CD progressors (CDP, children who developed CD during or after their gut microbiota were sampled) in each developmental phase. Pathogenesis and inflammation-related microbial pathways were enriched in CDP. Moreover, they had significantly more IgA coated bacteria and the IgA targets were significantly different compared to controls. Proinflammatory and pathogenesis-related metabolic pathways were enriched in CDP. Further, we identified inflammatory metabolites, particularly microbiota-derived taurodeoxycholic acid (TDCA) as increased in CDP.ConclusionOur study defines an inflammatory gut microbiota for the CDP including its composition, function, IgA response and related plasma metabolites. The inflammatory nature of CD gut microbiota during development is potentially related to the onset of the disease. Targeting inflammatory bacteria in this critical window could affect the pathogenesis and prognosis of CD.Significance of this studyWhat is already known on this subject?Celiac Disease (CD) is a gluten induced immune-mediated disease in genetically predisposed individuals.CD incidence is increasing worldwide which genetics alone cannot explain. Previous studies have shown that the gut microbiota of CD patients differ from that of healthy populations. However, the role of the microbiome in CD pathogenesis and its role in chronic inflammation is yet be established.What are the new findings?In a prospective longitudinal study in children using samples representing all three phases of gut microbiota development (ages 1, 2.5 and 5), we identified significant differences in the composition and function of gut microbiota at each phase. Pathogenesis and inflammation-related functions are enriched in the gut microbiome of CD progressors.We applied IgA-sequencing to identify inflammatory bacteria in both healthy subjects and CD progressors. Flow Cytometry analysis identified more IgA coated bacteria at ages 1 and 5 in CD progressors, indicating an early inflammatory response. CD bacterial IgA targets also differed significantly from healthy controls.We analyzed plasma metabolites obtained at age 5. The CD plasma metabolome was significantly different from healthy controls. Particularly, proinflammatory plasma metabolites, including microbiota-derived taurodeoxycholic acid (TDCA) and isobutyryl-L-carnitine, were increased two-fold in CD progressors.How might it impact clinical practice in the foreseeable future?Our results establish a link between gut microbiota composition and chronic inflammation in CD during child development. The highly IgA-coated bacteria identified in IgA sequencing and inflammatory bacteria potentially contribute to CD pathogenesis. Targeting these bacteria in the early stages of CD development could be a preventative tool.TDCA is a microbiota-derived proinflammatory metabolite increased two-fold in CD progressors. Increased TDCA levels may be used as a predictive/diagnostic tool in genetically predisposed subjects. Moreover, targeting TDCA-producing bacteria (e.g., Clostridium XIVa species) could potentially help to control the intestinal inflammation in CD.Developing anti-inflammatory probiotics/prebiotics might be viable therapeutics for altering microbiota composition in children genetically predisposed for CD. These microbes/compounds may also complement a gluten-free diet in patients that continue to experience persistent CD symptoms.

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The Main Anthocyanin Monomer from Lycium ruthenicum Murray Fruit Mediates Obesity via Modulating the Gut Microbiota and Improving the Intestinal Barrier

Foods ◽

10.3390/foods11010098 ◽

2021 ◽

Vol 11 (1) ◽

pp. 98

Author(s):

Peiyun Liu ◽

Wangting Zhou ◽

Weiqi Xu ◽

Yujia Peng ◽

Yamei Yan ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Body Weight Gain ◽

Liver Steatosis ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Beneficial Effects ◽

Lycium Ruthenicum ◽

First Time ◽

Gut Microbiota Composition

Anthocyanins have been shown to exert certain antiobesity properties, but the specific relationship between anthocyanin-induced beneficial effects and the gut microbiota remains unclear. Petunidin-3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(β-D-glucopyranoside) (P3G) is the main anthocyanin monomer from the fruit of Lycium ruthenicum Murray. Therefore, in this study, we investigated the antiobesity and remodeling effects of P3G on gut microbiota through a high-fat diet (HFD)-induced obesity mouse model and a fecal microbiota transplantation experiment. P3G was found to reduce body weight gain, fat accumulation, and liver steatosis in HFD-induced obese mice. Moreover, supplementation with P3G alleviated the HFD-induced imbalance in gut microbiota composition, and transferring the P3G-regulated gut microbiota to recipient mice provided comparable protection against obesity. This is the first time evidence is provided that P3G has an antiobesity effect by changing the intestinal microbiota. Our present data highlight a link between P3G intervention and enhancement in gut barrier integrity. This may be a promising option for obesity prevention.

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The Gut Microbiota: How Does It Influence the Development and Progression of Liver Diseases

Biomedicines ◽

10.3390/biomedicines8110501 ◽

2020 ◽

Vol 8 (11) ◽

pp. 501

Author(s):

Paulraj Kanmani ◽

Kanmani Suganya ◽

Hojun Kim

Keyword(s):

Gut Microbiota ◽

Liver Diseases ◽

Intestinal Inflammation ◽

Lipoteichoic Acid ◽

Short Chain Fatty Acids ◽

Bidirectional Relationship ◽

Host Health ◽

Cellular Components ◽

Gut Microbiota Composition

The gut–liver axis plays important roles in both the maintenance of a healthy liver and the pathogenesis of liver diseases, where the gut microbiota acts as a major determinant of this relationship. Gut bacteria-derived metabolites and cellular components are key molecules that affect the function of the liver and modulate the pathology of liver diseases. Accumulating evidence showed that gut microbiota produces a myriad of molecules, including lipopolysaccharide, lipoteichoic acid, peptidoglycan, and DNA, as well as short-chain fatty acids, bile acids, trimethylamine, and indole derivatives. The translocation of these components to the liver exerts beneficial or pathogenic effects by interacting with liver immune cells. This is a bidirectional relationship. Therefore, the existence of crosstalk between the gut and liver and its implications on host health and diseases are essential for the etiology and treatment of diseases. Several mechanisms have been proposed for the pathogenesis of liver diseases, but still, the mechanisms behind the pathogenic role of gut-derived components on liver pathogenesis remain elusive and not understandable. This review discusses the current progress on the gut microbiota and its components in terms of the progression of liver diseases, and in turn, how liver diseases indirectly affect the intestinal function and induce intestinal inflammation. Moreover, this paper highlights the current therapeutic and preventive strategies used to restore the gut microbiota composition and improve host health.

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Role of Dietary Nutritional Treatment on Hepatic and Intestinal Damage in Transplantation with Steatotic and Non-Steatotic Liver Grafts from Brain Dead Donors

Nutrients ◽

10.3390/nu13082554 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2554

Author(s):

Marc Micó-Carnero ◽

Araní Casillas-Ramírez ◽

Albert Caballeria-Casals ◽

Carlos Rojano-Alfonso ◽

Alfredo Sánchez-González ◽

...

Keyword(s):

Growth Factor ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Mucosal Damage ◽

Hepatic Damage ◽

Intestinal Damage ◽

Edema Formation ◽

Steatotic Liver ◽

Damage And Failure

Herein, we investigate whether: (1) the administration of glucose or a lipid emulsion is useful in liver transplantation (LT) using steatotic (induced genetically or nutritionally) or non-steatotic livers from donors after brain death (DBDs); and (2) any such benefits are due to reductions in intestinal damage and consequently to gut microbiota preservation. In recipients from DBDs, we show increased hepatic damage and failure in the maintenance of ATP, glycogen, phospholipid and growth factor (HGF, IGF1 and VEGFA) levels, compared to recipients from non-DBDs. In recipients of non-steatotic grafts from DBDs, the administration of glucose or lipids did not protect against hepatic damage. This was associated with unchanged ATP, glycogen, phospholipid and growth factor levels. However, the administration of lipids in steatotic grafts from DBDs protected against damage and ATP and glycogen drop and increased phospholipid levels. This was associated with increases in growth factors. In all recipients from DBDs, intestinal inflammation and damage (evaluated by LPS, vascular permeability, mucosal damage, TLR4, TNF, IL1, IL-10, MPO, MDA and edema formation) was not shown. In such cases, potential changes in gut microbiota would not be relevant since neither inflammation nor damage was evidenced in the intestine following LT in any of the groups evaluated. In conclusion, lipid treatment is the preferable nutritional support to protect against hepatic damage in steatotic LT from DBDs; the benefits were independent of alterations in the recipient intestine.

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Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients ◽

10.3390/nu13020690 ◽

2021 ◽

Vol 13 (2) ◽

pp. 690

Author(s):

Umair Shabbir ◽

Muhammad Sajid Arshad ◽

Aysha Sameen ◽

Deog-Hwan Oh

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiota ◽

Dietary Habits ◽

Inflammatory Responses ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Gut Dysbiosis ◽

Dynamic Population

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

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