Browsing by Subject "microbiota"

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  • Holster, Savanne; Hooiveld, Guido J.; Repsilber, Dirk; de Vos, Willem M.; Brummer, Robert J.; König, Julia (2019)
    Faecal microbiota transfer (FMT) consists of the introduction of new microbial communities into the intestine of a patient, with the aim of restoring a disturbed gut microbiota. Even though it is used as a potential treatment for various diseases, it is unknown how the host mucosa responds to FMT. This study aims to investigate the colonic mucosa gene expression response to allogenic (from a donor) or autologous (own) FMT in patients with irritable bowel syndrome (IBS). In a recently conducted randomised, double-blinded, controlled clinical study, 17 IBS patients were treated with FMT by colonoscopy. RNA was isolated from colonic biopsies collected by sigmoidoscopy at baseline, as well as two weeks and eight weeks after FMT. In patients treated with allogenic FMT, predominantly immune response-related gene sets were induced, with the strongest response two weeks after the FMT. In patients treated with autologous FMT, predominantly metabolism-related gene sets were affected. Furthermore, several microbiota genera showed correlations with immune-related gene sets, with different correlations found after allogenic compared to autologous FMT. This study shows that the microbe-host response is influenced by FMT on the mucosal gene expression level, and that there are clear differences in response to allogenic compared to autologous FMT.
  • Bui, Thi Phuong Nam; Troise, Antonio Dario; Fogliano, Vincenzo; de Vos, Willem M. (2019)
    Modifications of lysine contribute to the amount of dietary advanced glycation end-products reaching the colon. However, little is known about the ability of intestinal bacteria to metabolize dietary N-epsilon-carboxymethyllysine (CML). Successive transfers of fecal microbiota in growth media containing CML were used to identify and isolate species able to metabolize CML under anaerobic conditions. From our study, only donors exposed to processed foods degraded CML, and anaerobic bacteria enrichments from two of them used 77 and 100% of CML. Oscillibacter and Cloacibacillus evryensis increased in the two donors after the second transfer, highlighting that the bacteria from these taxa could be candidates for anaerobic CML degradation. A tentative identification of CML metabolites produced by a pure culture of Cloacibacillus evryensis was performed by mass spectrometry: carboxymethylated biogenic amines and carboxylic acids were identified as CML degradation products. The study confirmed the ability of intestinal bacteria to metabolize CML under anoxic conditions.
  • Mertsalmi, Tuomas H.; Pekkonen, Eero; Scheperjans, Filip (2020)
    Background Gut microbiota alterations have been found in prodromal and established Parkinson's disease (PD). Antibiotic exposure can have long-term effects on the composition of human intestinal microbiota, but a potential connection between antibiotic exposure and risk of PD has not been studied previously. Objective To evaluate the impact of antibiotic exposure on the risk of PD in a nationwide, register-based, case-control study. Methods We identified all patients who were diagnosed with PD in Finland during the years 1998 to 2014. Information was obtained on individual purchases of orally administered antibiotics during the years 1993 to 2014. We assessed the association between prior antibiotic exposure and PD using conditional logistic regression. Results The study population consisted of 13,976 PD cases and 40,697 controls. The strongest connection with PD risk was found for oral exposure to macrolides and lincosamides (adjusted odds ratio up to 1.416; 95% confidence interval, 1.053-1.904). After correction for multiple comparisons, exposure to antianaerobics and tetracyclines 10 to 15 years before the index date, sulfonamides and trimethoprim 1 to 5 years before the index date, and antifungal medications 1 to 5 years before the index date were positively associated with PD risk. In post hoc analyses, further positive associations were found for broad-spectrum antibiotics. Conclusions Exposure to certain types of oral antibiotics seems to be associated with an elevated risk of PD with a delay that is consistent with the proposed duration of a prodromal period. The pattern of associations supports the hypothesis that effects on gut microbiota could link antibiotics to PD, but further studies are needed to confirm this. (c) 2019 International Parkinson and Movement Disorder Society
  • Koponen, Kari (Helsingin yliopisto, 2020)
    BACKGROUND: Diet has a major influence on the human gut microbiome, which has been linked to health and disease. However, epidemiological studies on the association of a healthy diet with the gut microbiome utilizing a whole-diet approach are still scant. OBJECTIVES: To assess associations between healthy food choices and human gut microbiome composition, and to determine the strength of association with the functional potential of the microbiome. DESIGN: The study sample consisted of 4,930 participants in the FINRISK 2002 study. Food intake was assessed using a food propensity questionnaire. Intake of food items recommended to be part of a healthy diet in the Nordic Nutrition Recommendations were transformed into a healthy food choices (HFC) score. Microbial diversity (alpha diversity) and compositional differences (beta diversity) and their associations with the HFC score and its components were assessed using linear regression and permutational multivariate analysis of variance (PERMANOVA). Associations between specific taxa and HFC were analyzed using multivariate associations with linear models (MaAsLin). Functional associations were derived from KEGG orthologies (KO) with linear regression models. RESULTS: Both microbial alpha (p = 1.90x10-4) and beta diversity (p ≤ 0.001) associated with HFC score. For alpha diversity, the strongest associations were observed for fiber-rich breads, poultry, fruits, and low-fat cheeses. For beta diversity, most prominent associations were observed for vegetables followed by berries and fruits. Genera with fiber-degrading and short-chain fatty acids (SCFA) producing capacity were positively associated with the HFC score. HFC associated positively with KO-based functions such as vitamin biosynthesis and SCFA metabolism, and inversely with fatty acid biosynthesis and the sulfur relay system. CONCLUSIONS: These results from a large and representative population-based survey confirm and extend findings of other smaller-scale studies that plant and fiber-rich dietary choices are associated with a more diverse and compositionally distinct microbiome, and with a greater potential to produce SCFAs.
  • Koponen, Kari K.; Salosensaari, Aaro; Ruuskanen, Matti O.; Havulinna, Aki S.; Männistö, Satu; Jousilahti, Pekka; Palmu, Joonatan; Salido, Rodolfo; Sanders, Karenina; Brennan, Caitriona; Humphrey, Gregory C.; Sanders, Jon G.; Meric, Guillaume; Cheng, Susan; Inouye, Michael; Jain, Mohit; Niiranen, Teemu J.; Valsta, Liisa M.; Knight, Rob; Salomaa, Veikko V. (2021)
    Background: Diet has a major influence on the human gut microbiota, which has been linked to health and disease. However, epidemiological studies on associations of a healthy diet with the microbiota utilizing a whole-diet approach are still scant. Objectives: To assess associations between healthy food choices and human gut microbiota composition, and to determine the strength of association with functional potential. Methods: This population-based study sample consisted of 4930 participants (ages 25-74; 53% women) in the FINRISK 2002 study. Intakes of recommended foods were assessed using a food propensity questionnaire, and responses were transformed into healthy food choices (HFC) scores. Microbial diversity (alpha diversity) and compositional differences (beta diversity) and their associations with the HFC score and its components were assessed using linear regression. Multiple permutational multivariate ANOVAs were run from whole-metagenome shallow shotgun-sequenced samples. Associations between specific taxa and HFC were analyzed using linear regression. Functional associations were derived from Kyoto Encyclopedia of Genes and Genomes orthologies with linear regression models. Results: Both microbial alpha diversity (beta/SD, 0.044; SE, 6.18 x 10(-5); P = 2.21 x 10(-3)) and beta diversity (R-2, 0.12; P Conclusions: Our results from a large, population-based survey confirm and extend findings of other, smaller-scale studies that plant and fiber-rich dietary choices are associated with a more diverse and compositionally distinct microbiota, and with a greater potential to produce SCFAs.
  • Giaretta, Paula R.; Suchodolski, Jan S.; Jergens, Albert E.; Steiner, Jorg M.; Lidbury, Jonathan A.; Cook, Audrey K.; Hanifeh, Mohsen; Spillmann, Thomas; Kilpinen, Susanne; Syrja, Pernilla; Rech, Raquel R. (2020)
    The intestinal microbiota is believed to play a role in the pathogenesis of inflammatory bowel disease in humans and chronic inflammatory enteropathy (CIE) in dogs. While most previous studies have described the gut microbiota using sequencing methods, it is fundamental to assess the spatial distribution of the bacteria for a better understanding of their relationship with the host. The microbiota in the colonic mucosa of 22 dogs with CIE and 11 control dogs was investigated using fluorescence in situ hybridization (FISH) with a universal eubacterial probe (EUB338) and specific probes for select bacterial groups. The number of total bacteria labeled with EUB338 probe was lower within the colonic crypts of dogs with CIE compared to controls. Helicobacter spp. and Akkermansia spp. were decreased on the colonic surface and in the crypts of dogs with CIE. Dogs with CIE had increased number of Escherichia coli/Shigella spp. on the colonic surface and within the crypts compared to control dogs. In conclusion, the bacterial microbiota in the colonic mucosa differed between dogs with and without CIE, with depletion of the crypt bacteria in dogs with CIE. The crypt bacterial species that was intimately associated with the host mucosa in control dogs was composed mainly of Helicobacter spp.
  • Amatya, Sajeen Bahadur; Salmi, Sonja; Kainulainen, Veera; Karihtala, Peeter; Reunanen, Justus (2021)
    Simple Summary:& nbsp;Microbial dysbiosis has been credited as one of the contributing factors to the development and progression of gastrointestinal tract cancer. The altered microbiota influences carcinogenesis through the induction of instability and damage to genetic material, modulation of host metabolic and inflammatory pathways, production of carcinogenic metabolites, and suppression of host antitumor response. These microbes secrete extracellular vesicles that are possibly carrying carcinogenic bioactive metabolites within their cargo. Studies have illustrated the ability of bacterial extracellular vesicles to cross the intestinal epithelial barrier and selectively accumulate near intestinal tumor cells. The purpose of this systemic review was to highlight the possible role of gut bacterial vesicles in the development, progression, and pathogenesis of gastrointestinal tract cancer and their possible involvement in the modulation of the tumor microenvironment. An infinitesimal amount of research has been carried out on the impact of bacterial extracellular vesicles on oncogenesis and tumor progression. This review aimed to encourage more investigations on this subject.Bacterial extracellular vesicles are membrane-enclosed, lipid bi-layer nanostructures that carry different classes of biomolecules, such as nucleic acids, lipids, proteins, and diverse types of small molecular metabolites, as their cargo. Almost all of the bacteria in the gut secrete extracellular vesicles to assist them in competition, survival, material exchange, host immune modulation, infection, and invasion. The role of gut microbiota in the development, progression, and pathogenesis of gastrointestinal tract (GIT) cancer has been well documented. However, the possible involvement of bacterial extracellular vesicles (bEVs) in GIT cancer pathophysiology has not been given due attention. Studies have illustrated the ability of bEVs to cross physiological barriers, selectively accumulate near tumor cells, and possibly alter the tumor microenvironment (TME). A systematic search of original published works related to bacterial extracellular vesicles on gastrointestinal cancer was performed for this review. The current systemic review outlines the possible impact of gut microbiota derived bEVs in GIT cancer in light of present-day understanding. The necessity of using advanced sequencing technologies, such as genetic, proteomic, and metabolomic investigation methodologies, to facilitate an understanding of the interrelationship between cancer-associated bacterial vesicles and gastrointestinal cancer is also emphasized. We further discuss the clinical and pharmaceutical potential of bEVs, along with future efforts needed to understand the mechanism of interaction of bEVs in GIT cancer pathogenesis.
  • Biesiekierski, Jessica R.; Jalanka, Jonna; Staudacher, Heidi M. (2019)
    Dietary intervention is a challenge in clinical practice because of inter-individual variability in clinical response. Gut microbiota is mechanistically relevant for a number of disease states and consequently has been incorporated as a key variable in personalised nutrition models within the research context. This paper aims to review the evidence related to the predictive capacity of baseline microbiota for clinical response to dietary intervention in two specific health conditions, namely, obesity and irritable bowel syndrome (IBS). Clinical trials and larger predictive modelling studies were identified and critically evaluated. The findings reveal inconsistent evidence to support baseline microbiota as an accurate predictor of weight loss or glycaemic response in obesity, or as a predictor of symptom improvement in irritable bowel syndrome, in dietary intervention trials. Despite advancement in quantification methodologies, research in this area remains challenging and larger scale studies are needed until personalised nutrition is realistically achievable and can be translated to clinical practice.
  • Jalanka, Jonna; Cheng, Jing; Hiippala, Kaisa; Ritari, Jarmo; Salojärvi, Jarkko; Ruuska, Tarja; Kalliomaki, Marko; Satokari, Reetta (2020)
    Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n= 26) and non-IBD controls (n= 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA,p= 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC.
  • Kampmann, C.; Dicksved, J.; Engstrand, L.; Rautelin, H. (2016)
    In mice, specific species composition of gut microbiota enhances susceptibility to Campylobacter jejuni but little is known about the specific composition of the human gut microbiota in providing protection from infections caused by enteropathogens. Healthy adult individuals, who travelled in groups from Sweden to destinations with an estimated high risk for acquisition of Campylobacter infection, were enrolled. Faecal samples, collected before travelling and after returning home, were cultured for bacterial enteropathogens, and analysed for Campylobacter by PCR and for the species composition of the microbiota by 16S amplicon massive parallel sequencing. The microbiota compositions were compared between persons who became infected during their travel and those who did not. A total of 63 participants completed the study; 14 became infected with Campylobacter, two with Salmonella and 47 remained negative for the enteropathogens tested. After exclusion of samples taken after antimicrobial treatment, 49 individuals were included in the final analyses. Intra-individual stability of the microbiota was demonstrated for samples taken before travelling. The original diversity of the faecal microbiota was significantly lower among individuals who later became infected compared with those who remained uninfected. The relative abundances of bacteria belonging to the family Lachnospiraceae, and more specifically its two genera Dorea and Coprococcus, were significantly higher among those who remained uninfected. The travel-related infection did not significantly modify the faecal microbiota composition. Species composition of human gut microbiota is important for colonization resistance to Campylobacter infection. Especially individuals with a lower diversity are more susceptible to Campylobacter infection. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.
  • Ruokolainen, Lasse; Parkkola, Anna; Karkman, Antti; Sinkko, Hanna; Peet, Aleksandr; Hämäläinen, Anu-Maaria; von Hertzen, Leena; Tillmann, Vallo; Koski, Katriina; Virtanen, Suvi M.; Niemelä, Onni; Haahtela, Tari; Knip, Mikael (2020)
    Background Allergic diseases are more common in Finland than in Estonia, which-according to the biodiversity hypothesis-could relate to differences in early microbial exposures. Methods We aimed at defining possible microbial perturbations preceding early atopic sensitization. Stool, nasal and skin samples of 6-month-old DIABIMMUNE study participants with HLA susceptibility to type 1 diabetes were collected. We compared microbiotas of sensitized (determined by specific IgE results at 18 months of age) and unsensitized Estonian and Finnish children. Results Sensitization was differentially targeted between populations, as egg-specific and birch pollen-specific IgE was more common in Finland. Microbial diversity and community composition also differed; the genusAcinetobacterwas more abundant in Estonian skin and nasal samples. Particularly, the strain-level profile ofAcinetobacter lwoffiiwas more diverse in Estonian samples. Early microbiota was not generally associated with later sensitization. Microbial composition tended to differ between children with or without IgE-related sensitization, but only in Finland. While land-use pattern (ie green areas vs. urban landscapes around the children's homes) was not associated with microbiota as a whole, it associated with the composition of the genusAcinetobacter. Breastfeeding affected gut microbial composition and seemed to protect from sensitization. Conclusions In accordance with the biodiversity hypothesis, our results support disparate early exposure to environmental microbes between Finnish and Estonian children and suggest a significant role of the genusAcinetobacterin the allergy gap between the two populations. The significance of the observed differences for later allergic sensitization remains open.
  • Viitasalo, Liisa; Iltanen, Sari; Huhtala, Heini; Saavalainen, Päivi; Kaukinen, Katri; Lindfors, Katri; Kurppa, Kalle (2020)
    Risk of celiac disease (CD) is increased in relatives of CD patients due to genetic and possible environmental factors. We recently reported increased seropositivity to anti-Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (anti-I2) and Bacteroides caccae TonB-linked outer membrane protein (anti-OmpW) antibodies in CD. We hypothesized these markers also to be overrepresented in relatives. Seropositivity and levels of ASCA, anti-I2 and anti-OmpW were compared between 463 first-degree relatives, 58 untreated and 55 treated CD patients, and 80 controls. CD-associated human leukocyte antigen (HLA)-haplotypes and transglutaminase (tTGab) and endomysium (EmA) antibodies were determined. One or more of the microbial antibodies was present in 75% of relatives, 97% of untreated and 87% of treated CD patients and 44% of the controls. The relatives had higher median ASCA IgA (9.13 vs. 4.50 U/mL, p <0.001), ASCA IgG (8.91 vs. 5.75 U/mL, p <0.001) and anti-I2 (absorbance 0.74 vs. 0.32, p <0.001) levels than controls. There was a weak, positive correlation between tTGab and ASCA (r = 0.31, p <0.001). Seropositivity was not significantly associated with HLA. To conclude, seropositivity to microbial markers was more common and ASCA and anti-I2 levels higher in relatives of CD patients than controls. These findings were not associated with HLA, suggesting the role of other genetic and environmental factors.
  • Terhonen, Eeva; Blumenstein, Kathrin; Kovalchuk, Andriy; Asiegbu, Fred O. (2019)
    Terrestrial plants including forest trees are generally known to live in close association with microbial organisms. The inherent features of this close association can be commensalism, parasitism or mutualism. The term microbiota has been used to describe this ecological community of plant-associated pathogenic, mutualistic, endophytic and commensal microorganisms. Many of these microbiota inhabiting forest trees could have a potential impact on the health of, and disease progression in, forest biomes. Comparatively, studies on forest tree microbiomes and their roles in mutualism and disease lag far behind parallel work on crop and human microbiome projects. Very recently, our understanding of plant and tree microbiomes has been enriched due to novel technological advances using metabarcoding, metagenomics, metatranscriptomics and metaproteomics approaches. In addition, the availability of massive DNA databases (e.g., NCBI (USA), EMBL (Europe), DDBJ (Japan), UNITE (Estonia)) as well as powerful computational and bioinformatics tools has helped to facilitate data mining by researchers across diverse disciplines. Available data demonstrate that plant phyllosphere bacterial communities are dominated by members of only a few phyla (Proteobacteria, Actinobacteria, Bacteroidetes). In bulk forest soil, the dominant fungal group is Basidiomycota, whereas Ascomycota is the most prevalent group within plant tissues. The current challenge, however, is how to harness and link the acquired knowledge on microbiomes for translational forest management. Among tree-associated microorganisms, endophytic fungal biota are attracting a lot of attention for their beneficial health- and growth-promoting effects, and were preferentially discussed in this review.
  • Raju, Sajan C.; Lagström, Sonja; Ellonen, Pekka; de Vos, Willem M.; Eriksson, Johan G.; Weiderpass, Elisabete; Rounge, Trine B. (2019)
    Objective: The human intestinal microbiota likely play an important role in the development of overweight and obesity. However, the associations between saliva microbiota and body mass index (BMI) have been sparsely studied. The aim of this study was to identify the associations between saliva microbiota and body size in Finnish children. Methods: The saliva microbiota of 900 Finnish children, aged 11-14 years with measured height and weight, was characterized using 16S rRNA (V3-V4) sequencing. Results: The core saliva microbiota consisted of 14 genera that were present in more than 95% of the Finnish children. The saliva microbiota profiles were gender-specific with higher alpha-diversity in boys than girls and significant differences between the genders in community composition and abundances. Alpha-diversity differed between normal weight and overweight girls and between normal weight and obese boys. The composition was dissimilar between normal weight and obese girls, but not in boys. The relative abundance profiles differed according to body size. Decrease in commensal saliva bacteria were observed in all the body sizes when compared to normal weight children. Notably, the relative abundance of bacteria related to, Veillonella, Prevotella, Selenomonas, and Streptococcus was reduced in obese children. Conclusion: Saliva microbiota diversity and composition were significantly associated with body size and gender in Finnish children. Body size-specific saliva microbiota profiles open new avenues for studying the potential roles of microbiota in weight development and management.
  • Afrizal (Helsingin yliopisto, 2017)
    Bacteria are dominant members of the human gut microbiota, defined as the complex communities of microorganisms in the intestine which play an important role in regulating the health of their host, including the development of colorectal cancer (CRC). CRC is the fourth leading cancer-related mortality worldwide. Animal models are very useful in CRC research, as they allow studying molecular mechanism underlying the disease. Due to closer similarity to human beings in terms of nutrition and gastrointestinal physiology, pig models are of great value in research when compared with murine models. However, our current knowledge of the pig gut microbiome is still limited and a large number of gut bacterial species are yet to be isolated and characterised. Here, we characterised bacteria isolated from the intestine of wildtype pigs and transgenic APC1311/+ siblings (APC pigs) that develop colonic adenomas. A total of 12 novel bacteria, including 1 member of a potentially novel family, were identified from 256 strains isolated using anaerobic culturing. In addition, five other bacteria with a standing name in the nomenclature but not yet included in the pig collection were added. A draft genome was generated for four of the novel bacteria and thereby the functional potential of strains and compared their similarity. In addition, the morphology, bile salt hydrolase (BSH), 7α-dehydroxylation, carbohydrate fermentation, prevalence and abundance of all strains were analysed. The draft genome analysis confirmed the novel species status of the four bacteria. Furthermore, it also revealed the presence of genes associated with BSH, antibiotic resistance, butyrate production and carbohydrate utilization. Only two of 12 tested bacteria were positive for BSH, while none of the two bacteria selected for fermentation experiments was positive for 7α-dehydroxylation. One isolate of the species Paraclostridium benzoelyticum was found to exhibit significantly higher tolerance to NaCl than the same species described in the literature. In terms of prevalence, almost all of the bacteria (16 of 17) seem to be rare in pig, even though they appeared to be more enriched in the pig intestine when compared with other host species. Interestingly, the majority of positive samples for the bacterium representing the potentially novel family originated from the intestine of elderly human individuals. Overall, we could show that a substantial number of novel bacteria can still be isolated by classical anaerobic culture techniques using multiple rich or selective media. Even though we were able to identify most of the isolated bacteria and performed several assays to describe their properties, additional phylogenetic and taxonomic tests and development of optimal media/conditions for the novel bacteria are required in order to gain a deeper understanding of the role of these bacteria in the intestinal microbial ecosystem.
  • Suh, Sang Heon; Choe, Kibaek; Hong, Seon Pyo; Jeong, Seung-hwan; Mäkinen, Taija; Kim, Kwang Soon; Alitalo, Kari; Surh, Charles D.; Koh, Gou Young; Song, Joo-Hye (2019)
    A lacteal is a blunt-ended, long, tube-like lymphatic vessel located in the center of each intestinal villus that provides a unique route for drainage of absorbed lipids from the small intestine. However, key regulators for maintaining lacteal integrity are poorly understood. Here, we explore whether and how the gut microbiota regulates lacteal integrity. Germ depletion by antibiotic treatment triggers lacteal regression during adulthood and delays lacteal maturation during the postnatal period. In accordance with compromised lipid absorption, the button-like junction between lymphatic endothelial cells, which is ultrastructurally open to permit free entry of dietary lipids into lacteals, is significantly reduced in lacteals of germ-depleted mice. Lacteal defects are also found in germ-free mice, but conventionalization of germ-free mice leads to normalization of lacteals. Mechanistically, VEGF-C secreted from villus macrophages upon MyD88-dependent recognition of microbes and their products is a main factor in lacteal integrity. Collectively, we conclude that the gut microbiota is a crucial regulator for lacteal integrity by endowing its unique microenvironment and regulating villus macrophages in small intestine.
  • Yu, Dahai; Meng, Xin; de Vos, Willem M.; Wu, Hao; Fang, Xuexun; Maiti, Amit K. (2021)
    Humans, throughout the life cycle, from birth to death, are accompanied by the presence of gut microbes. Environmental factors, lifestyle, age and other factors can affect the balance of intestinal microbiota and their impact on human health. A large amount of data show that dietary, prebiotics, antibiotics can regulate various diseases through gut microbes. In this review, we focus on the role of gut microbes in the development of metabolic, gastrointestinal, neurological, immune diseases and, cancer. We also discuss the interaction between gut microbes and the host with respect to their beneficial and harmful effects, including their metabolites, microbial enzymes, small molecules and inflammatory molecules. More specifically, we evaluate the potential ability of gut microbes to cure diseases through Fecal Microbial Transplantation (FMT), which is expected to become a new type of clinical strategy for the treatment of various diseases.
  • Sammallahti, Heidelinde; Kokkola, Arto; Rezasoltani, Sama; Ghanbari, Reza; Asadzadeh Aghdaei, Hamid; Knuutila, Sakari; Puolakkainen, Pauli; Sarhadi, Virinder Kaur (2021)
    Pancreatic cancer (PC) is an aggressive disease with a high mortality and poor prognosis. The human microbiome is a key factor in many malignancies, having the ability to alter host metabolism and immune responses and participate in tumorigenesis. Gut microbes have an influence on physiological functions of the healthy pancreas and are themselves controlled by pancreatic secretions. An altered oral microbiota may colonize the pancreas and cause local inflammation by the action of its metabolites, which may lead to carcinogenesis. The mechanisms behind dysbiosis and PC development are not completely clear. Herein, we review the complex interactions between PC tumorigenesis and the microbiota, and especially the question, whether and how an altered microbiota induces oncogenomic changes, or vice versa, whether cancer mutations have an impact on microbiota composition. In addition, the role of the microbiota in drug efficacy in PC chemo- and immunotherapies is discussed. Possible future scenarios are the intentional manipulation of the gut microbiota in combination with therapy or the utilization of microbial profiles for the noninvasive screening and monitoring of PC.
  • Freitag, Tobias L.; Hartikainen, Anna; Jouhten, Hanne; Sahl, Cecilia; Meri, Seppo; Anttila, Veli-Jukka; Mattila, Eero; Arkkila, Perttu; Jalanka, Jonna; Satokari, Reetta (2019)
    Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) and is also considered a potential treatment for a wide range of intestinal and systemic diseases. FMT corrects the microbial dysbiosis associated with rCDI, and the engraftment of donor microbiota is likely to play a key role in treatment efficacy. For disease indications other than rCDI, FMT treatment efficacy has been moderate. This may be partly due to stronger resilience of resident host microbiota in patients who do not suffer from rCDI. In rCDI, patients typically have undergone several antibiotic treatments prior to FMT, depleting the microbiota. In this study, we addressed the effect of broad-spectrum antibiotics (Ab) as a pre-treatment to FMT on the engraftment of donor microbiota in recipients. We conducted a pre-clinical study of FMT between two healthy mouse strains, Balb/c as donors and C57BL/6 as recipients, to perform FMT within the same species and to mimic interindividual FMT between human donors and patients. Microbiota composition was assessed with high-throughput 16S rDNA amplicon sequencing. The microbiota of Balb/c and C57BL/6 mice differed significantly, which allowed for the assessment of microbiota transplantation from the donor strain to the recipient. Our results showed that Ab-treatment depleted microbiota in C57BL/6 recipient mice prior to FMT. The diversity of microbiota did not recover spontaneously to baseline levels during 8 weeks after Ab-treatment, but was restored already at 2 weeks in mice receiving FMT. Interestingly, pre-treatment with antibiotics prior to FMT did not increase the overall similarity of the recipient's microbiota to that of the donor's, as compared with mice receiving FMT without Ab-treatment. Pre-treatment with Ab improved the establishment of only a few donor-derived taxa, such as Bifidobacterium, in the recipients, thus having a minor effect on the engraftment of donor microbiota in FMT. In conclusion, pre-treatment with broad-spectrum antibiotics did not improve the overall engraftment of donor microbiota, but did improve the engraftment of specific taxa. These results may inform future therapeutic studies of FMT.
  • Pussinen, Pirkko; Kopra, Elisa; Pietiäinen, Milla; Lehto, Markku; Zaric, Svetislav; Paju, Susanna; Salminen, Aino (2022)
    Lipopolysaccharide is a virulence factor of gram-negative bacteria with a crucial importance to the bacterial surface integrity. From the host's perspective, lipopolysaccharide plays a role in both local and systemic inflammation, activates both innate and adaptive immunity, and can trigger inflammation either directly (as a microbe-associated molecular pattern) or indirectly (by inducing the generation of nonmicrobial, danger-associated molecular patterns). Translocation of lipopolysaccharide into the circulation causes endotoxemia, which is typically measured as the biological activity of lipopolysaccharide to induce coagulation of an aqueous extract of blood cells of the assay. Apparently healthy subjects have a low circulating lipopolysaccharide activity, since it is neutralized and cleared rapidly. However, chronic endotoxemia is involved in the pathogenesis of many inflammation-driven conditions, especially cardiometabolic disorders. These include atherosclerotic cardiovascular diseases, obesity, liver diseases, diabetes, and metabolic syndrome, where endotoxemia has been recognized as a risk factor. The main source of endotoxemia is thought to be the gut microbiota. However, the oral dysbiosis in periodontitis, which is typically enriched with gram-negative bacterial species, may also contribute to endotoxemia. As endotoxemia is associated with an increased risk of cardiometabolic disorders, lipopolysaccharide could be considered as a molecular link between periodontal microbiota and cardiometabolic diseases.