Osteoporosis is a disease characterized by low bone mass and alterations of bone microarchitecture, with an increased risk of fractures. It is a multifactorial disorder that is more frequent in ...postmenopausal women but can be associated to other diseases (inflammatory and metabolic diseases). At present, several options are available to treat osteoporosis trying to block bone reabsorption and reduce the risk of fracture. Anyway, these drugs have safety and tolerance problems in long-term treatment. Recently, gut microbiota has been highlighted to have strong influence on bone metabolism, becoming a potential new target to modify bone mineral density. Such evidences are mainly based on mouse models, showing an involvement in modulating the interaction between the immune system and bone cells. Germ-free mice represent a basic model to understand the interaction between microbiota, immune system, and bone cells, even though data are controversial. Anyway, such models have unequivocally demonstrated a connection between such systems, even if the mechanism is unclear. Gut microbiota is a complex system that influences calcium and vitamin D absorption and modulates gut permeability, hormonal secretion, and immune response. A key role is played by the T helper 17 lymphocytes, TNF, interleukin 17, and RANK ligand system. Other important pathways include NOD1, NOD2, and Toll-like receptor 5. Prebiotics and probiotics are a wide range of substances and germs that can influence and modify microbiota. Several studies demonstrated actions by different prebiotics and probiotics in different animals, differing according to sex, age, and hormonal status. Data on the effects on humans are poor and controversial. Gut microbiota manipulation appears a possible strategy to prevent and treat osteopenia and/or osteoporosis as well as other possible bone alterations, even though further clinical studies are necessary to identify correct procedures in humans.
Pancreatic cancer (PC) has an unfavorable prognosis with few effective therapeutic options. This has led researchers to investigate the possible links between microbiota and PC. A disrupted gut ...microbiome can lead to chronic inflammation, which is involved in the pathogenesis of PC. In addition, some bacterial strains can produce carcinogens that promote the growth of cancer cells. Research has also focused on pancreatic and oral microbiota. Changes in these microbiota can contribute to the development and progression of PC. Furthermore, patients with periodontal disease have an increased risk of developing PC. The potential use of microbiota as a prognostic marker or to predict patients' responses to chemotherapy or immunotherapy is also being explored. Overall, the role of microbiota-including the gut, pancreatic, and oral microbiota-in PC is an active research area. Understanding these associations could lead to new diagnostic and therapeutic targets for this deadly disease.
Summary
Background
Faecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota ...transplantation is effective in this disease, factors affecting its response are unknown.
Aims
To establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success.
Methods
This is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre‐treatment (FMT‐group, n = 17) vs antibiotic pre‐treatment only (AB‐group, n = 10) in 27 therapy refractory ulcerative colitis patients over 90 days. Faecal samples of donors and patients were analysed by 16SrRNA gene‐based microbiota analysis.
Results
In the FMT‐group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946 ± 93 vs no response 797 ± 181 at 15367 rps) and a high relative abundance of Akkermansia muciniphila (3.3 ± 3.1% vs 0.1 ± 0.2%), unclassified Ruminococcaceae (13.8 ± 5.0% vs 7.5 ± 3.7%), and Ruminococcus spp. (4.9 ± 3.5% vs 1.0 ± 0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB‐group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness.
Conclusions
The taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis.
Abstract Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential ...relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis CA1-CA3, dentate gyrus (DG), entorhinal cortex, hippocampal–amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae ) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium ) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.
Recent advancements in next-generation sequencing (NGS) have provided the foundation for modern studies into the composition of microbial communities. The use of these NGS methods allows for the ...detection and identification of (‘difficult-to-culture’) microorganisms using a culture-independent strategy. In the field of routine clinical diagnostics however, the application of NGS is currently limited to microbial strain typing for epidemiological purposes only, even though the implementation of NGS for microbial community analysis may yield clinically important information. This lack of NGS implementation is due to many different factors, including issues relating to NGS method standardization and result reproducibility. In this review article, the authors provide a general introduction to the most widely used NGS methods currently available (i.e., targeted amplicon sequencing and shotgun metagenomics) and the strengths and weaknesses of each method is discussed. The focus of the publication then shifts toward 16S rRNA gene NGS methods, which are currently the most cost-effective and widely used NGS methods for research purposes, and are therefore more likely to be successfully implemented into routine clinical diagnostics in the short term. In this respect, the experimental pitfalls and biases created at each step of the 16S rRNA gene NGS workflow are explained, as well as their potential solutions. Finally, a novel diagnostic microbiota profiling platform (‘MYcrobiota’) is introduced, which was developed by the authors by taking into consideration the pitfalls, biases, and solutions explained in this article. The development of the MYcrobiota, and future NGS methodologies, will help pave the way toward the successful implementation of NGS methodologies into routine clinical diagnostics.
The human intestine is host to an enormously complex, diverse, and vast microbial community-the gut microbiota. The gut microbiome plays a profound role in metabolic processing, energy production, ...immune and cognitive development, epithelial homeostasis, and so forth. However, the composition and diversity of the gut microbiome can be readily affected by external factors, which raises the possibility that exposure to toxic environmental chemicals leads to gut microbiome alteration, or dysbiosis. Arsenic exposure affects large human populations worldwide and has been linked to a number of diseases, including cancer, diabetes, and cardiovascular disorders.
We investigated the impact of arsenic exposure on the gut microbiome composition and its metabolic profiles.
We used an integrated approach combining 16S rRNA gene sequencing and mass spectrometry-based metabolomics profiling to examine the functional impact of arsenic exposure on the gut microbiome.
16S rRNA gene sequencing revealed that arsenic significantly perturbed the gut microbiome composition in C57BL/6 mice after exposure to 10 ppm arsenic for 4 weeks in drinking water. Moreover, metabolomics profiling revealed a concurrent effect, with a number of gut microflora-related metabolites being perturbed in multiple biological matrices.
Arsenic exposure not only alters the gut microbiome community at the abundance level but also substantially disturbs its metabolic profiles at the function level. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism by which arsenic exposure leads to or exacerbates human diseases.
Lu K, Abo RP, Schlieper KA, Graffam ME, Levine S, Wishnok JS, Swenberg JA, Tannenbaum SR, Fox JG. 2014. Arsenic exposure perturbs the gut microbiome and its metabolic profile in mice: an integrated metagenomics and metabolomics analysis. Environ Health Perspect 122:284-291; http://dx.doi.org/10.1289/ehp.1307429.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The early-life microbiota exerts a profound and lifelong impact on host health. Longitudinal studies in humans have been informative but are mostly based on the analysis of fecal samples and cannot ...shed direct light on the early development of mucosa-associated intestinal microbiota and its impact on GI function. Using piglets as a model for human infants, we assess here the succession of mucosa-associated microbiota across the intestinal tract in the first 35 days after birth.
Although sharing a similar composition and predicted functional profile at birth, the mucosa-associated microbiome in the small intestine (jejunum and ileum) remained relatively stable, while that of the large intestine (cecum and colon) quickly expanded and diversified by day 35. Among detected microbial sources (milk, vagina, areolar skin, and feces of sows, farrowing crate, and incubator), maternal milk microbes were primarily responsible for the colonization of the small intestine, contributing approximately 90% bacteria throughout the first 35 days of the neonatal life. Although maternal milk microbes contributed greater than 90% bacteria to the large intestinal microbiota of neonates upon birth, their presence gradually diminished, and they were replaced by maternal fecal microbes by day 35. We found strong correlations between the relative abundance of specific mucosa-associated microbes, particularly those vertically transmitted from the mother, and the expression levels of multiple intestinal immune and barrier function genes in different segments of the intestinal tract.
We revealed spatially specific trajectories of microbial colonization of the intestinal mucosa in the small and large intestines, which can be primarily attributed to the colonization by vertically transmitted maternal milk and intestinal microbes. Additionally, these maternal microbes may be involved in the establishment of intestinal immune and barrier functions in neonates. Our findings strengthen the notion that studying fecal samples alone is insufficient to fully understand the co-development of the intestinal microbiota and immune system and suggest the possibility of improving neonatal health through the manipulation of maternal microbiota.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Coronavirus disease 2019 (COVID‐19) is caused by respiratory syndrome coronavirus qualified as SARS‐CoV‐2. Viral penetration requires binding of the viral spike (S) protein to a specific cellular ...receptor (ACE2) highly expressed in a nasal goblet and ciliated cells. In several countries, the COVID‐19 evolution was relatively benign compared to others and despite noncompliance with health recommendations on several occasions. In this overview, we attempt to define the criteria that could explain such a difference. Among these criteria, the specificity of Lactobacillus genus strains, as a part of nasal microbiota, could play a role of a barrier against viral penetration and could strengthen the host's immune system in some populations rather than others. In fact, several studies have shown the role of lactic acid bacteria, including lactobacilli, in the prevention of viral respiratory infections. This could provide important information on a possible mechanism of the virus spreading.
Highlights • The behaviour and physiology of young and aged mice were compared, with an emphasis on gut microbiota, gut permeability and markers of peripheral inflammation. • Aged male mice exhibited ...impaired cognitive function and increased anxiety-like behaviour in comparison with young adult mice. • Gut permeability was increased in aged mice and was exacerbated by acute stress exposure. • Gut permeability was positively correlated with increases in plasma proinflammatory cytokines IL-6, IL-1β and TNF-α. • Gut microbiota was altered in aged mice, with increases in phylum TM7, family Porphyromonadaceae and genus Odoribacter , which have been implicated in inflammatory disorders and cognitive impairments. • Relative abundance of Porphyromonadaceae was significantly correlated with anxiety-like behaviour of aged mice.
•This is a review of the latest evidence for gut microbiota in depression.•A total of 16 clinical trials with 1003 participants were included.•Family Prevotellaceae,and genus Coprococcus and ...Faecalibacterium were lower in depression compared with controls.•Probiotics interventions reduced depressive symptoms compared with controls.
Growing attention has been paid to the field of gut microbiota for mental disorders over the last decade. However, to our knowledge, no studies have conducted systematic reviews on the association between gut microbiota and major depressive disorder (MDD) in both interventional and non-interventional studies.
We conducted a systematic review and meta-analysis of 16 studies (10 observational 701 participants and six interventional trials 302 participants) examining gut microbiota in patients with MDD. The primary outcome measures were differences in the profile of microbiota in the observational studies, and symptom changes for depression between pre- and post-intervention with probiotics in the interventional trials.
In the observational studies, significant reductions in several taxa at the family and genus levels were observed in patients with MDD compared to non-depressed controls. In the interventional studies with probiotics, a significant improvement was found in depressive symptomatology compared to controls (SMD = -1.62, 95% CI = -2.73 to -0.51, p< 0.01).
Lack of consideration of the effects of diet and pharmacotherapy was a possible limitation.
Our results indicate that several taxa at the family and genus levels, specifically family Prevotellaceae, genus Corprococcus, and Faecalibacterium, were decreased in MDD compared to non-depressed controls in observational studies, and depressive symptoms were improved compared to controls in interventional studies with probiotics. Due to the limited number of studies, further studies considering diet and pharmacotherapy are needed to explore the relationships between gut microbiota and MDD in humans.
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