Gut Microbiota Composition Correlates with Disease Severity in Myelodysplastic Syndrome.

The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Microbial signals, such as lipopolysaccharides from gram-negative bacteria, can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. To test this hypothesis, we sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls. We observed a negative correlation between Prevotella spp. and Akkermansia spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus Prevotella spp. compared to the other risk categories. There was a significant reduction in the abundance of the genus Akkermansia spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus Ruminococcus spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria.

Metagenome-assembled genomes (MAGs) suggest an acetate-driven protective role in gut microbiota disrupted by Clostridioides difficile.

Clostridioides difficile may have a negative impact on gut microbiota composition in terms of diversity and abundance, thereby triggering functional changes supported by the differential presence of genes involved in significant metabolic pathways, such as short-chain fatty acids (SCFA). This work has evaluated shotgun metagenomics data regarding 48 samples from four groups classified according to diarrhea acquisition site (community- and healthcare facility-onset) and positive or negative Clostridioides difficile infection (CDI) result. The metagenomic-assembled genomes (MAGs) obtained from each sample were taxonomically assigned for preliminary comparative analysis concerning differences in composition among groups. The predicted genes involved in metabolism, transport, and signaling remained constant in microbiota members; characteristic patterns were observed in MAGs and genes involved in SCFA butyrate and acetate metabolic pathways for each study group. A decrease in genera and species, as well as relative MAG abundance with the presence of the acetate metabolism-related gene, was evident in the HCFO/- group. Increased antibiotic resistance markers (ARM) were observed in MAGs along with the genes involved in acetate metabolism. The results highlight the need to explore the role of acetate in greater depth as a potential protector of the imbalances produced by CDI, as occurs in other inflammatory intestinal diseases.

Deficiency of IL-22-binding protein enhances the ability of the gut microbiota to protect against enteric pathogens.

Interleukin 22 (IL-22) promotes intestinal barrier integrity, stimulating epithelial cells to enact defense mechanisms against enteric infections, including the production of antimicrobial peptides. IL-22 binding protein (IL-22BP) is a soluble decoy encoded by the Il22ra2 gene that decreases IL-22 bioavailability, attenuating IL-22 signaling. The impact of IL-22BP on gut microbiota composition and functioning is poorly understood. We found that Il22ra2-/- mice are better protected against Clostridioides difficile and Citrobacter rodentium infections. This protection relied on IL-22-induced antimicrobial mechanisms before the infection occurred, rather than during the infection itself. Indeed, the gut microbiota of Il22ra2-/- mice mitigated infection of wild-type (WT) mice when transferred via cohousing or by cecal microbiota transplantation. Indicator species analysis of WT and Il22ra2-/- mice with and without cohousing disclosed that IL22BP deficiency yields a gut bacterial composition distinct from that of WT mice. Manipulation of dietary fiber content, measurements of intestinal short-chain fatty acids and oral treatment with acetate disclosed that resistance to C. difficile infection is related to increased production of acetate by Il22ra2-/--associated microbiota. Together, these findings suggest that IL-22BP represents a potential therapeutic target for those at risk for or with already manifest infection with this and perhaps other enteropathogens.

The Interplay between Gut Microbiota and Cognitive Functioning in the Healthy Aging Population: A Systematic Review.

BACKGROUND: The gut microbiota in healthy older individuals typically show a decrease in beneficial bacteria like Bifidobacterium and Lactobacillus, alongside an increase in pro-inflammatory microbes such as Enterobacteriaceae and Clostridia. These changes contrast with younger and middle-aged individuals and appear to correlate with cognitive status. Although there is extensive research on gut microbiota and cognitive functions in cognitively impaired elderly individuals, its impact on cognitively healthy elderly populations has not been extensively studied. METHOD: A comprehensive literature search was conducted across PubMed, EBSCO, Web of Science, and Scopus databases to identify studies exploring the relationship between gut microbiota composition and cognitive functioning in healthy older adults. During the literature screening process, each record was initially assessed by its title, abstract, and keywords to exclude articles that did not align with the scope of this review. Three authors independently screened and retrieved the records. The inclusion criteria included: (1) publication in peer-reviewed journals; (2) studies involving neurologically, cognitively, and medically healthy populations; (3) participants identified as older adults, defined for this review as individuals aged 45 years and older due to the limited number of records; (4) analysis of gut microbiota; and (5) assessment of cognitive function. Subsequently, full texts were analyzed to determine eligibility. The exclusion criteria encompassed: (1) incorrect publication type; (2) inappropriate sample population; (3) unsuitable study design; (4) absence of one or more inclusion criteria; and (5) studies based on animal research. A risk of bias assessment was performed for each included study using the Joanna Briggs Institute (JBI) checklist, ensuring all selected studies met established quality standards. RESULTS: A total of 6 eligible research articles from a possible 1752 published until March 2024 were identified and included. We categorized the included studies into two groups based on their focus: the taxonomic composition of gut microbiota and the alpha diversity, which is the variety of organisms within a sample. Additionally, two methods were identified for assessing cognition: neuropsychological tests and physiological measurements, notably electroencephalography (EEG). The studies show varying results regarding the abundance of specific bacterial taxa and their cognitive associations. Notably, the relationship between certain bacteria and cognition may vary when analyzed at different taxonomic levels, such as phylum versus family. CONCLUSIONS: Changes in gut microbiota composition in the elderly, even without a cognitive impairment diagnosis, could potentially serve as early biological markers for Alzheimer's disease or other dementias before mild cognitive impairment appears.

Role of traditional Chinese medicine in age-related macular degeneration: exploring the gut microbiota's influence.

The pathogenesis of age-related macular degeneration (AMD), a degenerative retinopathy, remains unclear. Administration of anti-vascular endothelial growth factor agents, antioxidants, fundus lasers, photodynamic therapy, and transpupillary warming has proven effective in alleviating symptoms; however, these interventions cannot prevent or reverse AMD. Increasing evidence suggests that AMD risk is linked to changes in the composition, abundance, and diversity of the gut microbiota (GM). Activation of multiple signaling pathways by GM metabolites, including lipopolysaccharides, oxysterols, short-chain fatty acids (SCFAs), and bile acids (BAs), influences retinal physiology. Traditional Chinese medicine (TCM), known for its multi-component and multi-target advantages, can help treat AMD by altering GM composition and regulating the levels of certain substances, such as lipopolysaccharides, reducing oxysterols, and increasing SCFA and BA contents. This review explores the correlation between GM and AMD and interventions for the two to provide new perspectives on treating AMD with TCM.

The relationship between gut microbiota, short-chain fatty acids, and glucolipid metabolism in pregnant women with large for gestational age infants.

AIM: To elucidate the association between gut microbiota, short-chain fatty acids (SCFAs), and glucolipid metabolism in women with large for gestational age (LGA) infants. METHODS AND RESULTS: A single-center, observational prospective cohort study was performed at a tertiary hospital in Wenzhou, China. Normal pregnant women were divided into LGA group and appropriate for gestational age (AGA) group according to the neonatal birth weight. Fecal samples were collected from each subject before delivery for the analysis of gut microbiota composition (GMC) and SCFAs. Blood samples were obtained at 24-28 weeks of gestation age to measure fasting blood glucose and fasting insulin levels, as well as just before delivery to assess serum triglycerides, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein. The GMC exhibited differences at various taxonomic levels. Within the Firmicutes phylum, genus Lactobacillus, genus Clostridium, species Lactobacillus agil, and species Lactobacillus salivarius were enriched in the LGA group. Microbispora at genus level, Microbispora rosea at species level belonging to the Actinobacteria phylum, Neisseriales at order level, Bartonellaceae at family level, Paracoccus aminovorans, and Methylobacterium at genus level from the Proteobacteria phylum were more abundant in the LGA group. In contrast, within the Bacteroidetes phylum, Prevotella at genus level and Parabacteroides distasonis at species level were enriched in the AGA group. Although there were few differences observed in SCFA levels and most glucolipid metabolism indicators between the two groups, the serum HDL level was significantly lower in the LGA group compared to the AGA group. No significant relevance among GMC, SCFAs, and glucolipid metabolism indicators was found in the LGA group or in the AGA group. CONCLUSIONS: Multiple different taxa, especially phylum Firmicutes, genus Prevotella, and genus Clostridium, might play an important role in excessive fetal growth, and LGA might be associated with the lower serum HDL level.

The Immunomodulatory Effect of ß-Glucan Depends on the Composition of the Gut Microbiota.

This study aimed to elucidate the relationship between the immunomodulatory effects of ß-glucan and the composition of gut microbiota in mice. The mice were fed a diet containing ß-glucan for 3 weeks, and feces, blood, and tissues were then collected to analyze the immunomodulatory effect and gut microbiota composition. Based on the results of the analysis of the expression level of immune-associated proteins, the high immunomodulatory effect group (HIE) and low immunomodulatory effect group (LIE) were categorized. Before the ß-glucan diet, the proportions of the phylum Bacteroidota, family Muribaculaceae, and family Lactobacillaceae were significantly higher in HIE than in LIE. Furthermore, the genus Akkermansia was absent before the ß-glucan diet and increased after ß-glucan diet. These microbes had the ability to metabolize ß-glucan or were beneficial to health. In conclusion, our findings demonstrate that variation in the composition of gut microbiota among individuals can result in varying expressions of ß-glucan functionality. This outcome supports the notion that ß-glucan may be metabolized through diverse pathways by gut microbes originally possessed by mice, subsequently producing various metabolites, such as short-chain fatty acids. Alternatively, the viscosity of the intestinal mucosa could be enhanced by ß-glucan, potentially promoting the growth of certain bacteria (e.g., the genus Akkermansia). This study provides insights into the intricate interplay between ß-glucan, gut microbiota, and immunomodulation.

Psychological Stress and Gut Microbiota Composition: A Systematic Review of Human Studies.

INTRODUCTION: The associations between psychological stress and gut microbiota composition are not fully understood. This study investigated associations between psychological stress and gut microbiota composition and examined the potential modifying effects of age, sex, and ethnicity on such associations. METHODS: A systematic literature search was conducted using PubMed, Web of Science, PsycINFO, and Embase databases for studies published until November 2021 which examined associations between psychological stress and gut microbiota composition. RESULTS: During the search process, 10,790 studies were identified, and after screening, 13 met the eligibility criteria and were included. The median sample size was 70, and the median age of participants was 28.0 years. Most of the included studies did not report associations between measures of alpha- and beta diversity of the gut microbiota composition and psychological stress. A few studies reported that the Shannon index, Chao 1, Simpson index, and weighted UniFrac were negatively associated with psychological stress. Significant reductions in several taxa at the phyla-, family-, and genus-levels were observed in participants with higher psychological stress. At the phylum level, the abundance of Proteobacteria and Verrucomicrobia were negatively associated with psychological stress. At the family-level, no more than two studies reported associations of the same microbiota with psychological stress. At the genus level, the following results were found in more than two studies; psychological stress was negatively associated with the abundance of Lachnospira, Lachnospiraceae, Phascolarctobacterium, Sutterella, and Veillonella, and positively associated with the abundance of Methanobrevibacter, Rhodococcus, and Roseburia. However, it was not possible to determine the influence of age, sex, or ethnicity due to the limited studies included. CONCLUSION: Our findings provide evidence that psychological stress is associated with changes in the abundance of the gut microbiota. Larger sample longitudinal studies are needed to determine the causal relationship between psychological stress and the gut microbiota.

Antioxidant Activity, Metabolism, and Bioavailability of Polyphenols in the Diet of Animals.

As the world's population grows, so does the need for more and more animal feed. In 2006, the EU banned the use of antibiotics and other chemicals in order to reduce chemical residues in food consumed by humans. It is well known that oxidative stress and inflammatory processes must be combated to achieve higher productivity. The adverse effects of the use of pharmaceuticals and other synthetic compounds on animal health and product quality and safety have increased interest in phytocompounds. With the use of plant polyphenols in animal nutrition, they are gaining more attention as a supplement to animal feed. Livestock feeding based on a sustainable, environmentally friendly approach (clean, safe, and green agriculture) would also be a win-win for farmers and society. There is an increasing interest in producing healthier products of animal origin with a higher ratio of polyunsaturated fatty acids (PUFAs) to saturated fatty acids by modulating animal nutrition. Secondary plant metabolites (polyphenols) are essential chemical compounds for plant physiology as they are involved in various functions such as growth, pigmentation, and resistance to pathogenic organisms. Polyphenols are exogenous antioxidants that act as one of the first lines of cell defense. Therefore, the discoveries on the intracellular antioxidant activity of polyphenols as a plant supplement have contributed significantly to the improvement of antioxidant activity, as polyphenols prevent oxidative stress damage and eliminate excessively produced free radicals. To achieve animal welfare, reduce stress and the need for medicines, and increase the quality of food of animal origin, the addition of polyphenols to research and breeding can be practised in part with a free-choice approach to animal nutrition.

The effect of combined dietary supplementation of herbal additives on carcass traits, meat quality, immunity and cecal microbiota composition in Hungarian white geese.

The present study was performed to investigate the effects of dietary supplementation with herbal additives on meat quality, slaughter performance and the cecal microbial community in Hungarian white geese. A total of 60 newborn geese were assigned equally into the control group (CON) and the herbal complex supplemented group (HS). The dietary supplementations consisted of Compound Herbal Additive A (CHAA) including Pulsatilla, Gentian and Rhizoma coptidis, and Compound Herbal Additive B (CHAB) containing Codonopsis pilosula, Atractylodes, Poria cocos and Licorice. The geese in the HS group received a basal diet supplemented with 0.2% CHAA from day 0 to day 42 at the postnatal stage. Then from day 43 to day 70, the geese in HS group were provide a basal diet with 0.15% CHAB. The geese in the CON group were only provided with the basal diet. The results showed that the slaughter rate (SR), half chamber rates (HCR), eviscerated rate (ER) and breast muscle rate (BMR) in the HS group tended to increase slightly compared with the CON group (ns). In addition, the shear force, filtration rate and pH value of breast muscle and thigh muscle in the HS group were slightly enhanced compared to the CON group (ns). Significant increased levels in carbohydrate content, fat content and energy (P < 0.01) and significant decreased levels in cholesterol content (P < 0.01) were observed in the muscle of the HS group. The total amino acid (Glu, Lys, Thr and Asp) content in the muscle increased in HS group than in the CON group (P < 0.01). Dietary herb supplementations significantly increased the levels of IgG in serum (P < 0.05) on day 43 and higher levels of IgM, IgA and IgG (P < 0.01) were also observed in the HS group on day 70. Furthermore, 16S rRNA sequencing results indicated that herbal additives increased the growth of beneficial bacteria and inhibited the proliferation of harmful bacteria in the geese caecum. Altogether, these results offer crucial insights into the potential benefits of incorporating CHAA and CHAB into the diets of Hungarian white goose. The findings indicate that such supplementations could significantly improve meat quality, regulate the immune system and shape the intestinal microbiota composition.

Methodological challenges in neonatal microbiome research.

Following microbial colonization at birth, the gut microbiome plays a vital role in the healthy development of human neonates and impacts both health and disease in later life. Understanding the development of the neonatal gut microbiome and how it interacts with the neonatal host are therefore important areas of study. However, research within this field must address a range of specific challenges that impact the design and implementation of research methods. If not considered ahead of time, these challenges have the potential to introduce biases into studies, negatively affecting the relevance, reproducibility, and impact of any findings. This review outlines the nature of these challenges and points to current and future solutions, as outlined in the literature, to assist researchers in the early stages of study design.

Inferring causal structures of gut microbiota diversity and feed efficiency traits in poultry using Bayesian learning and genomic structural equation models.

Feed and phosphorus (P) efficiency are of increasing importance in poultry breeding. It has been shown recently that these efficiency traits are influenced by the gut microbiota composition of the birds. The efficiency traits and the gut microbiota composition are partly under control of the host genome. Thus, the gut microbiota composition can be seen as a mediator trait between the host genome and the efficiency traits. The present study used data from 749 individuals of a Japanese quail F2 cross. The birds were genotyped for 4k single-nucleotide polymorphism (SNP) and trait recorded for P utilization (PU) and P retention (PR), body weight gain (BWG), and feed per gain ratio (F:G). The gut microbiota composition was characterized by targeted amplicon sequencing. The alpha diversity was calculated as the Pielou's evenness index (J'). A stable Bayesian network was established using a Hill-Climbing learning algorithm. Pielou's evenness index was placed as the most upstream trait and BWG as the most downstream trait, with direct and indirect links via PR, PU, and F:G. The direct and indirect effects between J', PU, and PR were quantified with structural equation models (SEM), which revealed a causal link from J' to PU and from PU to PR. Quantitative trait loci (QTL) linkage mapping revealed three genome-wide significant QTL regions for these traits with in total 49 trait-associated SNP within the QTL regions. SEM association mapping separated the total SNP effect for a trait into a direct effect and indirect effects mediated by upstream traits. Although the indirect effects were in general small, they contributed to the total SNP effect in some cases. This enabled us to detect some shared genetic effects. The method applied allows for the detection of shared genetic architecture of quantitative traits and microbiota compositions.

Feed efficiency and phosphorus efficiency are of increasing importance in poultry breeding. It was frequently shown that next to the birds' genomes also the gut microbiota composition is important for these efficiency traits. The gut microbiota composition is a mediator between the genomes of the birds and their efficiency traits. In the present study, an approach was taken to consider the animal's gut microbiota diversity, efficiency traits, and the genomes of the animals together in a causal network to decipher the mediator role between the traits. Growing Japanese quail were used as model species. A stable network could be established that placed the diversity of the gut microbiota composition at the forefront, with direct and indirect links to other traits like phosphorus utilization and retention, feed per gain ratio, and growth. Together with genome scans, the results confirmed the mediator role of the gut microbiota composition because several traits associated variants affected the efficiency traits directly and indirectly via the gut microbiota composition.

Gut microbiome and stages of diabetes in middle-aged adults: CARDIA microbiome study.

BACKGROUND: Animal and human studies suggest the gut microbiome is linked to diabetes but additional data are needed on the associations of the gut microbiome to specific diabetes characteristics. The aim of this study was to examine the associations of gut microbiome composition to insulin resistance [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], duration of diabetes, and 4 stages of diabetes [normoglycemia, pre-diabetes, and diabetes with (+) and without (-) medication for diabetes]. METHODS: Data are from a sub-sample (n = 605) of Black and White participants from the 30-year follow-up exam of the prospectively followed community-based Coronary Artery Risk Development in Young Adults cohort (2015-2016; aged 48-60 years). Stool samples were collected and sequenced using the 16S ribosomal RNA method. Microbial measures included: α diversity (within-person), ß diversity (between-person), and taxonomies. All analyses were adjusted for demographic, clinical, lifestyle factors, and use of relevant medications (full adjustment). Multivariate linear regression models were used to assess the association of diabetes characteristics with α diversity and genera abundance, while the association with ß diversity was analyzed using permutational multivariate analysis of variance. Statistical significance was set to p-value < 0.05 for α and ß diversity analyses and to q-value < 0.1 for genera abundance analyses. RESULTS: There were 16.7% of participants with pre-diabetes, and 14.4% with diabetes (9% diabetes+) with median (interquartile range) diabetes duration of 5 (5-10) years. In the fully adjusted models, compared to those with no diabetes, longer diabetes duration and the diabetes + group had a lower α diversity. There were significant differences in ß diversity across diabetes-related characteristics. A significantly reduced abundance of butyrate-producing genera was associated with higher HOMA-IR (ex., Anaerostipes and Lachnospiraceae_UCG.004), longer diabetes duration (ex., Agathobacter and Ruminococcus), and diabetes + (ex., Faecalibacterium and Romboutsia). CONCLUSIONS: Our results suggest that an adverse alteration of gut microbiome composition is related to higher insulin resistance, longer diabetes duration, and is present in those persons with diabetes using medications. These diabetes-related characteristics were also associated with lower levels of certain butyrate-producing bacteria that produce health-promoting short-chain fatty acids. Understanding the role of gut microbiota in glucose regulation may provide new strategies to reduce the burden of diabetes.

Trimethylamine N-Oxide as a Potential Risk Factor for Non-communicable Diseases: A Systematic Review.

BACKGROUND: Trimethylamine N-Oxide (TMAO), as a gut microbiota-derived metabolite, has been associated with a number of chronic diseases like cardiovascular diseases. OBJECTIVE: Considering the increasing prevalence of non-communicable diseases (NCDs), we conducted a systematic review to discuss the TMAO association with NCDs. METHODS: A comprehensive search has been conducted on PubMed, Web of Science, and Scopus databases up to December, 2020. The inclusion criteria were all related observational studies that surveyed the association between TMAO levels and non-communicable diseases. Interventional studies, animal experiments, reviews, case reports, letters, congress abstracts, and studies that were not published in English were excluded. Moreover, related review studies were separately discussed. RESULTS: Within 2191 recorded studies, 99 cross-sectional, case-control and cohort studies met the inclusion criteria. The most common diseases associated with TMAO levels are cardiovascular diseases, diabetes, kidney disease, stroke, inflammatory diseases, neurological disorders, and cancer. Elevated TMAO levels as a consequence of alteration in gut microbiota composition and dietary intake can lead to the incidence of NCDs. The high levels of TMAO can disrupt the homeostasis of glucose and lipids and induce inflammation that leads to serious NCDs. CONCLUSION: There is a dose-response relationship between TMAO levels and NCDs progression. Therefore, it can be studied as a therapeutic target or prognostic biomarker for dealing with NCDs.

In vivo evidence of the prevents DSS-induced colitis of Lactiplantibacillus plantarum L15.

Ulcerative colitis (UC) is challenging to treat and severely impacts patients and families. A previous study reported immunomodulatory and reduction of pro-inflammatory properties for the Lactiplantibacillus plantarum L15. This study aimed to analyze the preventive properties and mechanistic actions in an in vivo colitis model. The histopathological alteration, inflammation cytokines, and intestinal barrier function were analyzed. Subsequently, the cecal gut microbiota contents and products from different groups were detected. Finally, gene expressions related to the NF-κB signaling process were evaluated. L. plantarum L15 significantly decreased disease activity index (DAI), myeloperoxidase activity (MPO), pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) level, and increased weight change, colon length, and production of inflammation-suppressing cytokines. Furthermore, this strain supplementation substantially increased ZO-1, Occludin, and Claudin-1, and MUC2 mRNA expression levels with a corresponding decrease in serum lipopolysaccharide and D-lactic acid contents. In addition, L. plantarum L15 improved gut microbiota composition and increased short-chain fatty acid (SCFAs) in the colon content, which significantly reduced the transfer of NF-κB p65 to the nucleus. Our findings provide a theoretical basis for L. plantarum L15 as a preventive candidate for UC.

Modulation of the intestinal microbiota impacts the efficacy of immunotherapy in cancer patients - A recent literature survey.

In line with the current development of individualized cancer treatments, targeted and specialized therapeutic regimens such as immunotherapy gain importance and factors improving its efficacy come into the focus of actual research. Given the orchestrated interaction of the intestinal microbiota with host immunity the modulation of the human gut microbiota represents a therapy-enhancing factor. We therefore performed an actual literature survey on the role of the gut microbiota composition and the effects of its modification during immunotherapy of cancer patients. The included 23 studies published in the past 10 years revealed that both, distinct bacterial species and genera including Faecalibacterium prausnitzii and Bifidobacterium, respectively, enhanced distinct immunotherapy responses following PD-1/PD-L1 and CTLA-4 blockage, for instance, resulting in a better clinical outcome of cancer patients. Conversely, a high intestinal abundance of Bacteroidetes and Fusobacterium species correlated with a less efficient immunotherapy resulting in shorter progress-free survival outcomes. In conclusion, modifications of the gut microbiota by fecal microbiota transplantation or application of probiotic compounds represent potential adjunct options for immunotherapy in cancer patients which needs to be further addressed in future trials to provide individually tailored and safe adjuvant therapeutic measures in the combat of cancer.

A Systematic Review on the Effects of Different Types of Probiotics in Animal Alzheimer's Disease Studies.

Alzheimer's disease (AD) is a global public health priority as with aging populations, its prevalence is expected to rise even further in the future. The brain and gut are in close communication through immunological, nervous and hormonal routes, and therefore, probiotics are examined as an option to influence AD hallmarks, such as plaques, tangles, and low grade inflammation. This study aimed to provide an overview of the available animal evidence on the effect of different probiotics on gut microbiota composition, short chain fatty acids (SCFAs), inflammatory markers, Amyloid-ß (Aß), and cognitive functioning in AD animal models. A systematic literature search was performed in PubMed, SCOPUS, and APA PsychInfo. Articles were included up to May 2021. Inclusion criteria included a controlled animal study on probiotic supplementation and at least one of the abovementioned outcome variables. Of the eighteen studies, most were conducted in AD male mice models (n = 9). Probiotics of the genera Lactobacillus and Bifidobacterium were used most frequently. Probiotic administration increased species richness and/or bacterial richness in the gut microbiota, increased SCFAs levels, reduced inflammatory markers, and improved cognitive functioning in AD models in multiple studies. The effect of probiotic administration on Aß remains ambiguous. B. longum (NK46), C. butyricum, and the mixture SLAB51 are the most promising probiotics, as positive improvements were found on almost all outcomes. The results of this animal review underline the potential of probiotic therapy as a treatment option in AD.

Diurnal Interplay between Epithelium Physiology and Gut Microbiota as a Metronome for Orchestrating Immune and Metabolic Homeostasis.

The behavior and physiology of most organisms are temporally coordinated and aligned with geophysical time by a complex interplay between the master and peripheral clocks. Disruption of such rhythmic physiological activities that are hierarchically organized has been linked to a greater risk of developing diseases ranging from cancer to metabolic syndrome. Herein, we summarize the molecular clockwork that is employed by intestinal epithelial cells to anticipate environmental changes such as rhythmic food intake and potentially dangerous environmental stress. We also discuss recent discoveries contributing to our understanding of how a proper rhythm of intestinal stem cells may achieve coherence for the maintenance of tissue integrity. Emerging evidence indicates that the circadian oscillations in the composition of the microbiota may operate as an important metronome for the proper preservation of intestinal physiology and more. Furthermore, in this review, we outline how epigenetic clocks that are based on DNA methylation levels may extensively rewire the clock-controlled functions of the intestinal epithelium that are believed to become arrhythmic during aging.

Interactions between Enterohemorrhagic Escherichia coli (EHEC) and Gut Commensals at the Interface of Human Colonoids.

The interactions between the gut microbiota and pathogens are complex and can determine the outcome of an infection. Enterohemorrhagic Escherichia coli (EHEC) is a major human enteric pathogen that colonizes the colon through attaching and effacing (AE) lesions and uses microbiota-derived molecules as cues to control its virulence. Different gut commensals can modulate EHEC virulence. However, the lack of an animal model that recapitulates the human pathophysiology of EHEC infection makes it challenging to investigate how variations in microbiota composition could affect host susceptibility to this pathogen. Here, we addressed these interactions building from simple to more complex in vitro systems, culminating with the use of the physiological relevant human colonoids as a model to study the interactions between EHEC and different gut commensals. We demonstrated that Bacteroides thetaiotaomicron and Enterococcus faecalis enhance virulence expression and AE lesion formation in cultured epithelial cells, as well as on the colonic epithelium, while commensal E. coli did not affect these phenotypes. Importantly, in the presence of these three commensals together, virulence and AE lesion are enhanced. Moreover, we identified specific changes in the metabolic landscape promoted by different members of the gut microbiota and showed that soluble factors released by E. faecalis can increase EHEC virulence gene expression. Our study highlights the importance of interspecies bacterial interactions and chemical exchange in the modulation of EHEC virulence. IMPORTANCE Enterohemorrhagic E. coli (EHEC) is a natural human pathogen that poorly colonizes mice. Hence, the use of murine models to understand features of EHEC infection is a challenge. In this study, we use human colonoids as a physiologically relevant model to study interactions between EHEC and gut commensals. We demonstrate that the ability of EHEC to form AE lesions on the intestinal epithelium is enhanced by the presence of certain gut commensals, such as B. thetaiotaomicron and E. faecalis, while it is not affected by commensal E. coli. Furthermore, we show that commensal bacteria differently impact the metabolic landscape. These data suggest that microbiota compositions can differentially modulate EHEC-mediated disease.

Association between residential greenness and gut microbiota in Chinese adults.

BACKGROUND: A growing body of studies have reported the health benefits of greenness. However, less is known about the potential beneficial effects of residential greenness on gut microbiota, which is essential to human health. In this study, we aim to examine the association between residential greenness and gut microbiota in a population-based cohort study. METHODS: We included 1758 participants based on the China Multi-Ethnic Cohort (CMEC) study and collected their stool samples for 16S sequencing to derive gut microbiota data. Residential greenness was estimated using the satellite-based data on enhanced vegetation index (EVI) and the normalized differential vegetation index (NDVI) in circular buffers of 250 m, 500 m, and 1000 m. The relationships between residential greenness levels and the composition of gut microbiota, measured by standardized α-diversity and taxonomic composition, were assessed using linear regression and Spearman correlation weighted by generalized propensity scores. RESULTS: Higher greenness levels were significantly positively associated with standardized α-diversity. Per interquartile range (IQR) increase of EVI and NDVI in the circular buffer of 250 m were associated with the increments of 0.995(95% confidence interval (CI): 0.212-1.778) and 0.653(95% CI: 0.160-1.146) in the standardized Shannon index. For the taxonomic composition of gut microbiota, higher greenness levels were significantly correlated with 29 types of microbial taxonomic composition. NDVI in the circular buffer of 250 m was associated with increased Firmicutes (r = 0.102, adjusted p value = 0.004), which was the dominant composition in the gut microbiota. CONCLUSIONS: Increased amounts of residential greenness may support healthy gut microbiota by benignly altering their composition. These findings suggested that green spaces should be designed to support diverse gut microbiota and ultimately optimize health benefits.