The road not taken: host genetics in shaping intergenerational microbiomes.

The early-life gut microbiome is linked to human phenotypes as an imbalanced microbiome of this period is implicated in diseases throughout life. Several determinants of early-life gut microbiome are explored, however, mechanisms of acquisition, colonization, and stability of early-life gut microbiome and their interindividual variability remain elusive. Host genetics play a vital role to shape the gut microbiome and interact with it to modulate individual phenotypes in human studies and animal models. Given the microbial linkage between host generations, we discuss the current state of roles of host genetics in forming intergenerational microbiomes associated with mothers, offspring, and those vertically transmitted, providing a basis for taking into account host genetics in future early-life microbiome research. We further expand our discussion to the bidirectional interactions between host gene expression and microbiome in human health.

Synthesizing images of tau pathology from cross-modal neuroimaging using deep learning.

Given the prevalence of dementia and the development of pathology-specific disease-modifying therapies, high-value biomarker strategies to inform medical decision-making are critical. In vivo tau-PET is an ideal target as a biomarker for Alzheimer's disease diagnosis and treatment outcome measure. However, tau-PET is not currently widely accessible to patients compared to other neuroimaging methods. In this study, we present a convolutional neural network (CNN) model that imputes tau-PET images from more widely available cross-modality imaging inputs. Participants (n = 1192) with brain T1-weighted MRI (T1w), fluorodeoxyglucose (FDG)-PET, amyloid-PET and tau-PET were included. We found that a CNN model can impute tau-PET images with high accuracy, the highest being for the FDG-based model followed by amyloid-PET and T1w. In testing implications of artificial intelligence-imputed tau-PET, only the FDG-based model showed a significant improvement of performance in classifying tau positivity and diagnostic groups compared to the original input data, suggesting that application of the model could enhance the utility of the metabolic images. The interpretability experiment revealed that the FDG- and T1w-based models utilized the non-local input from physically remote regions of interest to estimate the tau-PET, but this was not the case for the Pittsburgh compound B-based model. This implies that the model can learn the distinct biological relationship between FDG-PET, T1w and tau-PET from the relationship between amyloid-PET and tau-PET. Our study suggests that extending neuroimaging's use with artificial intelligence to predict protein specific pathologies has great potential to inform emerging care models.

Seismic detection of a deep mantle discontinuity within Mars by InSight.

Constraining the thermal and compositional state of the mantle is crucial for deciphering the formation and evolution of Mars. Mineral physics predicts that Mars' deep mantle is demarcated by a seismic discontinuity arising from the pressure-induced phase transformation of the mineral olivine to its higher-pressure polymorphs, making the depth of this boundary sensitive to both mantle temperature and composition. Here, we report on the seismic detection of a midmantle discontinuity using the data collected by NASA's InSight Mission to Mars that matches the expected depth and sharpness of the postolivine transition. In five teleseismic events, we observed triplicated P and S waves and constrained the depth of this discontinuity to be 1,006 [Formula: see text] 40 km by modeling the triplicated waveforms. From this depth range, we infer a mantle potential temperature of 1,605 [Formula: see text] 100 K, a result consistent with a crust that is 10 to 15 times more enriched in heat-producing elements than the underlying mantle. Our waveform fits to the data indicate a broad gradient across the boundary, implying that the Martian mantle is more enriched in iron compared to Earth. Through modeling of thermochemical evolution of Mars, we observe that only two out of the five proposed composition models are compatible with the observed boundary depth. Our geodynamic simulations suggest that the Martian mantle was relatively cold 4.5 Gyr ago (1,720 to 1,860 K) and are consistent with a present-day surface heat flow of 21 to 24 mW/m2.

Reactive capture and electrochemical conversion of CO2 with ionic liquids and deep eutectic solvents.

Ionic liquids (ILs) and deep eutectic solvents (DESs) have tremendous potential for reactive capture and conversion (RCC) of CO2 due to their wide electrochemical stability window, low volatility, and high CO2 solubility. There is environmental and economic interest in the direct utilization of the captured CO2 using electrified and modular processes that forgo the thermal- or pressure-swing regeneration steps to concentrate CO2, eliminating the need to compress, transport, or store the gas. The conventional electrochemical conversion of CO2 with aqueous electrolytes presents limited CO2 solubility and high energy requirement to achieve industrially relevant products. Additionally, aqueous systems have competitive hydrogen evolution. In the past decade, there has been significant progress toward the design of ILs and DESs, and their composites to separate CO2 from dilute streams. In parallel, but not necessarily in synergy, there have been studies focused on a few select ILs and DESs for electrochemical reduction of CO2, often diluting them with aqueous or non-aqueous solvents. The resulting electrode-electrolyte interfaces present a complex speciation for RCC. In this review, we describe how the ILs and DESs are tuned for RCC and specifically address the CO2 chemisorption and electroreduction mechanisms. Critical bulk and interfacial properties of ILs and DESs are discussed in the context of RCC, and the potential of these electrolytes are presented through a techno-economic evaluation.

Stable Pentagonal Layered Palladium Diselenide Enables Rapid Electrosynthesis of Hydrogen Peroxide.

Electrosynthesis of hydrogen peroxide (H2O2) via the two-electron oxygen reduction reaction (2e- ORR) is promising for various practical applications, such as wastewater treatment. However, few electrocatalysts are active and selective for 2e- ORR yet are also resistant to catalyst leaching under realistic operating conditions. Here, a joint experimental and computational study reveals active and stable 2e- ORR catalysis in neutral media over layered PdSe2 with a unique pentagonal puckered ring structure type. Computations predict active and selective 2e- ORR on the basal plane and edge of PdSe2, but with distinct kinetic behaviors. Electrochemical measurements of hydrothermally synthesized PdSe2 nanoplates show a higher 2e- ORR activity than other Pd-Se compounds (Pd4Se and Pd17Se15). PdSe2 on a gas diffusion electrode can rapidly accumulate H2O2 in buffered neutral solution under a high current density. The electrochemical stability of PdSe2 is further confirmed by long device operational stability, elemental analysis of the catalyst and electrolyte, and synchrotron X-ray absorption spectroscopy. This work establishes a new efficient and stable 2e- ORR catalyst at practical current densities and opens catalyst designs utilizing the unique layered pentagonal structure motif.

Harnessing the endogenous Type I-C CRISPR-Cas system for genome editing in Bifidobacterium breve.

Bifidobacterium breve, one of the main bifidobacterial species colonizing the human gastrointestinal tract in early life, has received extensive attention for its purported beneficial effects on human health. However, exploration of the mode of action of such beneficial effects exerted by B. breve is cumbersome due to the lack of effective genetic tools, which limits its synthetic biology application. The widespread presence of CRISPR-Cas systems in the B. breve genome makes endogenous CRISPR-based gene editing toolkits a promising tool. This study revealed that Type I-C CRISPR-Cas systems in B. breve can be divided into two groups based on the amino acid sequences encoded by cas gene clusters. Deletion of the gene coding uracil phosphoribosyl-transferase (upp) was achieved in five B. breve strains from both groups using this system. In addition, translational termination of uracil phosphoribosyl-transferase was successfully achieved in B. breve FJSWX38M7 by single-base substitution of the upp gene and insertion of three stop codons. The gene encoding linoleic acid isomerase (bbi) in B. breve, being a characteristic trait, was deleted after plasmid curing, which rendered it unable to convert linoleic acid into conjugated linoleic acid, demonstrating the feasibility of successive editing. This study expands the toolkit for gene manipulation in B. breve and provides a new approach toward functional genome editing and analysis of B. breve strains.IMPORTANCEThe lack of effective genetic tools for Bifidobacterium breve is an obstacle to studying the molecular mechanisms of its health-promoting effects, hindering the development of next-generation probiotics. Here, we introduce a gene editing method based on the endogenous CRISPR-Cas system, which can achieve gene deletion, single-base substitution, gene insertion, and successive gene editing in B. breve. This study will facilitate discovery of functional genes and elucidation of molecular mechanisms of B. breve pertaining to health-associated benefits.

Promiscuous, persistent and problematic: insights into current enterococcal genomics to guide therapeutic strategy.

Vancomycin-resistant enterococci (VRE) are major opportunistic pathogens and the causative agents of serious diseases, such as urinary tract infections and endocarditis. VRE strains mainly include species of Enterococcus faecium and E. faecalis which can colonise the gastrointestinal tract (GIT) of patients and, following growth and persistence in the gut, can transfer to blood resulting in systemic dissemination in the body. Advancements in genomics have revealed that hospital-associated VRE strains are characterised by increased numbers of mobile genetic elements, higher numbers of antibiotic resistance genes and often lack active CRISPR-Cas systems. Additionally, comparative genomics have increased our understanding of dissemination routes among patients and healthcare workers. Since the efficiency of currently available antibiotics is rapidly declining, new measures to control infection and dissemination of these persistent pathogens are urgently needed. These approaches include combinatory administration of antibiotics, strengthening colonisation resistance of the gut microbiota to reduce VRE proliferation through commensals or probiotic bacteria, or switching to non-antibiotic bacterial killers, such as bacteriophages or bacteriocins. In this review, we discuss the current knowledge of the genomics of VRE isolates and state-of-the-art therapeutic advances against VRE infections.

Vascular leak in sepsis: physiological basis and potential therapeutic advances.

Sepsis is a life-threatening condition characterised by endothelial barrier dysfunction and impairment of normal microcirculatory function, resulting in a state of hypoperfusion and tissue oedema. No specific pharmacological therapies are currently used to attenuate microvascular injury. Given the prominent role of endothelial breakdown and microcirculatory dysfunction in sepsis, there is a need for effective strategies to protect the endothelium. In this review we will discuss key mechanisms and putative therapeutic agents relevant to endothelial barrier function.

Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota?

Many epidemiological studies have shown the beneficial effects of a largely plant-based diet, and the strong association between the consumption of a Mediterranean-type diet with healthy aging including a lower risk of cognitive decline. The Mediterranean diet is characterized by a high intake of olive oil, fruits and vegetables and is rich in dietary fiber and polyphenols - both of which have been postulated to act as important mediators of these benefits. Polyphenols are large molecules produced by plants to protect them from environmental threats and injury. When ingested by humans, as little as 5% of these molecules are absorbed in the small intestine with the majority metabolized by the gut microbiota into absorbable simple phenolic compounds. Flavan-3-ols, a type of flavonoid, contained in grapes, berries, pome fruits, tea, and cocoa have been associated with many beneficial effects on several risk factors for cardiovascular disease, cognitive function and brain regions involved in memory formation. Both preclinical and clinical studies suggest that these brain and heart benefits can be attributed to endothelial vascular effects and anti-inflammatory properties among others. More recently the gut microbiota has emerged as a potential modulator of the aging brain and intriguingly polyphenols have been shown to alter microbiota composition and be metabolized by different microbial species. However, there is a need for well controlled studies in large populations to identify predictors of response, particularly given the vast inter-individual variation of human gut microbiota.

Individual variation in the avian gut microbiota: The influence of host state and environmental heterogeneity.

The gut microbiota have important consequences for host biological processes and there is some evidence that they also affect fitness. However, the complex, interactive nature of ecological factors that influence the gut microbiota has scarcely been investigated in natural populations. We sampled the gut microbiota of wild great tits (Parus major) at different life stages allowing us to evaluate how microbiota varied with respect to a diverse range of key ecological factors of two broad types: (1) host state, namely age and sex, and the life history variables, timing of breeding, fecundity and reproductive success; and (2) the environment, including habitat type, the distance of the nest to the woodland edge, and the general nest and woodland site environments. The gut microbiota varied with life history and the environment in many ways that were largely dependent on age. Nestlings were far more sensitive to environmental variation than adults, pointing to a high degree of flexibility at an important time in development. As nestlings developed their microbiota from one to two weeks of life, they retained consistent (i.e., repeatable) among-individual differences. However these apparent individual differences were driven entirely by the effect of sharing the same nest. Our findings point to important early windows during development in which the gut microbiota are most sensitive to a variety of environmental drivers at multiple scales, and suggest reproductive timing, and hence potentially parental quality or food availability, are linked with the microbiota. Identifying and explicating the various ecological sources that shape an individual's gut bacteria is of vital importance for understanding the gut microbiota's role in animal fitness.

Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography.

OBJECTIVE: This study was undertaken to assess cross-sectional and longitudinal [18 F]-flortaucipir positron emission tomography (PET) uptake in pathologically confirmed frontotemporal lobar degeneration (FTLD) and to compare FTLD to cases with high and low levels of Alzheimer disease (AD) neuropathologic changes (ADNC). METHODS: One hundred forty-three participants who had completed at least one flortaucipir PET and had autopsy-confirmed FTLD (n = 52) or high (n = 58) or low ADNC (n = 33) based on Braak neurofibrillary tangle stages 0-IV versus V-VI were included. Flortaucipir standard uptake value ratios (SUVRs) were calculated for 9 regions of interest (ROIs): an FTLD meta-ROI, midbrain, globus pallidum, an AD meta-ROI, entorhinal, inferior temporal, orbitofrontal, precentral, and medial parietal. Linear mixed effects models were used to compare mean baseline SUVRs and annual rate of change in SUVR by group. Sensitivity and specificity to distinguish FTLD from high and low ADNC were calculated. RESULTS: Baseline uptake in the FTLD meta-ROI, midbrain, and globus pallidus was greater in FTLD than high and low ADNC. No region showed a greater rate of flortaucipir accumulation in FTLD. Baseline uptake in the AD-related regions and orbitofrontal and precentral cortices was greater in high ADNC, and all showed greater rates of accumulation compared to FTLD. Baseline differences were superior to longitudinal rates in differentiating FTLD from high and low ADNC. A simple baseline metric of midbrain/inferior temporal ratio of flortaucipir uptake provided good to excellent differentiation between FTLD and high and low ADNC (sensitivities/specificities = 94%/95% and 71%/70%). INTERPRETATION: There are cross-sectional and longitudinal differences in flortaucipir uptake between FTLD and high and low ADNC. However, optimum differentiation between FTLD and ADNC was achieved with baseline uptake rather than longitudinal rates. ANN NEUROL 2022;92:1016-1029.

The many faces of globular glial tauopathy: A clinical and imaging study.

BACKGROUND: Globular glial tauopathy (GGT) has been associated with frontotemporal dementia syndromes; little is known about the clinical and imaging characteristics of GGT and how they differ from other non-globular glial 4-repeat tauopathies (N4GT) such as progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). METHODS: For this case-control study the Mayo Clinic brain banks were queried for all cases with an autopsy-confirmed diagnosis of GGT between 1 January 2011 and 31 October 2021. Fifty patients with N4GT (30 PSP, 20 CBD) were prospectively recruited and followed by the Neurodegenerative Research Group at Mayo Clinic, Minnesota. Magnetic resonance imaging was used to characterize patterns of gray/white matter atrophy, MR-parkinsonism index, midbrain volume, and white matter hyperintensities.18 F-Fluorodeoxyglucose-, 11 C Pittsburg compound-, and 18 F-flortaucipir-positron emission tomography scans were reviewed. RESULTS: Twelve patients with GGT were identified: 83% were women compared to 42% in NG4T (p = 0.02) with median age at death 76.5 years (range: 55-87). The most frequent clinical features were eye movement abnormalities, parkinsonism, behavioral changes followed by pyramidal tract signs and motor speech abnormalities. Lower motor neuron involvement was present in 17% and distinguished GGT from NG4T (p = 0.035). Primary progressive apraxia of speech was the most frequent initial diagnosis (25%); 50% had a Parkinson-plus syndrome before death. Most GGT patients had asymmetric frontotemporal atrophy with matching hypometabolism. GGT patients had more gray matter atrophy in temporal lobes, normal MR-parkinsonism index, and larger midbrain volumes. CONCLUSIONS: Female sex, lower motor neuron involvement in the context of a frontotemporal dementia syndrome, and asymmetric brain atrophy with preserved midbrain might be suggestive of underlying GGT.

Microbiota-assisted therapy for systemic inflammatory arthritis: advances and mechanistic insights.

Research on the influence of gut microbiota on systemic inflammatory arthritis has exploded in the past decade. Gut microbiota changes may be a crucial regulatory component in systemic inflammatory arthritis. As a result of advancements in the field, microbiota-assisted therapy has evolved, but this discipline is still in its infancy. Consequently, we review the limitations of current systemic inflammatory arthritis treatment, analyze the connection between the microbiota and arthritis, and summarize the research progress of microbiota regulating systemic inflammatory arthritis and the further development aspects of microbiota-assisted therapy. Finally, the partial mechanisms of microbiota-assisted therapy of systemic inflammatory arthritis are being discussed. In general, this review summarizes the current progress, challenges, and prospects of microbiota-assisted therapy for systemic inflammatory arthritis and points out the direction for the development of microbiota-assisted therapy in the future.

Neonatal outcomes following introduction of routine probiotic supplementation to very preterm infants.

AIM: To evaluate the combined outcome of death and/or severe grade necrotising enterocolitis (NEC) in very preterm infants admitted to Cork University Maternity Hospital, Ireland, before and after introduction of routine supplementation with Bifidobacterium bifidum and Lactobacillus acidophilus probiotics (Infloran®). METHODS: A retrospective study of infants <32 weeks gestation and < 1500 g surviving beyond 72 h of life was performed. Two 6-year epochs; pre-probiotics (Epoch 1: 2008-2013) and with probiotics (Epoch 2: 2015-2020), were evaluated. The primary outcome was defined as death after 72 h or NEC Bell stage 2a or greater. RESULTS: Seven-hundred-and-forty-four infants were included (Epoch 1: 391, Epoch 2: 353). The primary outcome occurred in 67 infants (Epoch 1: 37, Epoch 2: 30, p = 0.646). After adjustment, the difference was significant (OR [95% CI]: 0.53 [0.29 to 0.97], p = 0.038). Differences between epochs did not depend on gestational age group (<28 weeks; ≥28 weeks). CONCLUSION: There was an associated reduction of the composite outcome of severe grade NEC and/or death, after adjustment for confounding variables, with introduction of routine administration of a B. bifidum and L. acidophilus probiotic at our institution.

Bioactivity Screening and Genomic Analysis Reveals Deep-Sea Fish Microbiome Isolates as Sources of Novel Antimicrobials.

With the increase in antimicrobial resistance and the subsequent demand for novel therapeutics, the deep-sea fish microbiome can be a relatively untapped source of antimicrobials, including bacteriocins. Previously, bacterial isolates were recovered from the gut of deep-sea fish sampled from the Atlantic Ocean.In this study, we used in vitro methods to screen a subset of these isolates for antimicrobial activity, and subsequently mined genomic DNA from isolates of interest for bacteriocin and other antimicrobial metabolite genes. We observed antimicrobial activity against foodborne pathogens, including Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis and Micrococcus luteus. In total, 147 candidate biosynthetic gene clusters were identified in the genomic sequences, including 35 bacteriocin/RiPP-like clusters. Other bioactive metabolite genes detected included non-ribosomal peptide synthases (NRPS), polyketide synthases (PKS; Types 1 and 3), beta-lactones and terpenes. Moreover, four unique bacteriocin gene clusters were annotated and shown to encode novel peptides: a class IIc bacteriocin, two class IId bacteriocins and a class I lanthipeptide (LanM subgroup). Our dual in vitro and in silico approach allowed for a more comprehensive understanding of the bacteriocinogenic potential of these deep-sea isolates and an insight into the antimicrobial molecules that they may produce.

Metabolomic Workflow for the Accurate and High-Throughput Exploration of the Pathways of Tryptophan, Tyrosine, Phenylalanine, and Branched-Chain Amino Acids in Human Biofluids.

The modulation of host and dietary metabolites by gut microbiota (GM) is important for maintaining correct host physiology and in the onset of various pathologies. An ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was developed for the targeted quantitation in human plasma, serum, and urine of 89 metabolites resulting from human-GM cometabolism of dietary essential amino acids tryptophan, tyrosine, and phenylalanine as well as branched-chain amino acids. Ninety-six-well plate hybrid-SPE enables fast clean-up of plasma and serum. Urine was diluted and filtered. A 15 min cycle enabled the acquisition of 96 samples per day, with most of the metabolites stable in aqueous solution for up to 72 h. Calibration curves were specifically optimized to cover expected concentrations in biological fluids, and limits of detection were at the order of ppb. Matrix effects were in acceptable ranges, and analytical recoveries were in general greater than 80%. Inter and intraday precision and accuracy were satisfactory. We demonstrated its application in plasma and urine samples obtained from the same individual in the frame of an interventional study, allowing the quantitation of 51 metabolites. The method could be considered the reference for deciphering changes in human-gut microbial cometabolism in health and disease. Data are available via Metabolights with the identifier MTBLS4399.

Operando Elucidation of Electrocatalytic and Redox Mechanisms on a 2D Metal Organic Framework Catalyst for Efficient Electrosynthesis of Hydrogen Peroxide in Neutral Media.

The practical electrosynthesis of hydrogen peroxide (H2O2) is hindered by the lack of inexpensive and efficient catalysts for the two-electron oxygen reduction reaction (2e- ORR) in neutral electrolytes. Here, we show that Ni3HAB2 (HAB = hexaaminobenzene), a two-dimensional metal organic framework (MOF), is a selective and active 2e- ORR catalyst in buffered neutral electrolytes with a linker-based redox feature that dynamically affects the ORR behaviors. Rotating ring-disk electrode measurements reveal that Ni3HAB2 has high selectivity for 2e- ORR (>80% at 0.6 V vs RHE) but lower Faradaic efficiency due to this linker redox process. Operando X-ray absorption spectroscopy measurements reveal that under argon gas the charging of the organic linkers causes a dynamic Ni oxidation state, but in O2-saturated conditions, the electronic and physical structures of Ni3HAB2 change little and oxygen-containing species strongly adsorb at potentials more cathodic than the reduction potential of the organic linker (Eredox ∼ 0.3 V vs RHE). We hypothesize that a primary 2e- ORR mechanism occurs directly on the organic linkers (rather than the Ni) when E > Eredox, but when E < Eredox, H2O2 production can also occur through Ni-mediated linker discharge. By operating the bulk electrosynthesis at a low overpotential (0.4 V vs RHE), up to 662 ppm of H2O2 can be produced in a buffered neutral solution in an H-cell due to minimized strong adsorption of oxygenates. This work demonstrates the potential of conductive MOF catalysts for 2e- ORR and the importance of understanding catalytic active sites under electrochemical operation.

Disbalance of the Duodenal Epithelial Cell Turnover and Apoptosis Accompanies Insensitivity of Intestinal Redox Homeostasis to Inhibition of the Brain Glucose-Dependent Insulinotropic Polypeptide Receptors in a Rat Model of Sporadic Alzheimer's Disease.

INTRODUCTION: Gastrointestinal dyshomeostasis is investigated in the context of metabolic dysfunction, systemic, and neuroinflammation in Alzheimer's disease. Dysfunctional gastrointestinal redox homeostasis and the brain-gut incretin axis have been reported in the rat model of insulin-resistant brain state-driven neurodegeneration induced by intracerebroventricular streptozotocin (STZ-icv). We aimed to assess whether (i) the structural epithelial changes accompany duodenal oxidative stress; (ii) the brain glucose-dependent insulinotropic polypeptide receptor (GIP-R) regulates redox homeostasis of the duodenum; and (iii) the STZ-icv brain-gut axis is resistant to pharmacological inhibition of the brain GIP-R. METHODS: GIP-R inhibitor [Pro3]-GIP (85 µg/kg) was administered intracerebroventricularly to the control and the STZ-icv rats 1 month after model induction. Thiobarbituric acid reactive substances (TBARSs) were measured in the plasma and duodenum, and the sections were analyzed morphometrically. Caspase-3 expression and activation were assessed by Western blot and multiplex fluorescent signal amplification. RESULTS: Intracerebroventricular [Pro3]-GIP decreased plasma TBARSs in the control and STZ-icv animals and increased duodenal TBARSs in the controls. In the controls, inhibition of brain GIP-R affected duodenal epithelial cells, but not villus structure, while all morphometric parameters were altered in the STZ-icv-treated animals. Morphometric changes in the STZ-icv animals were accompanied by reduced levels of caspase-3. Suppression of brain GIP-R inhibited duodenal caspase-3 activation. CONCLUSION: Brain GIP-R seems to be involved in the regulation of duodenal redox homeostasis and epithelial cell turnover. Resistance of the brain-gut GIP axis and morphological changes indicative of abnormal epithelial cell turnover accompany duodenal oxidative stress in the STZ-icv rats.

Exploiting lactic acid bacteria for colorectal cancer: a recent update.

Colorectal cancer (CRC) is the third most common cancer in the world. Currently, chemotherapy and radiotherapy used to treat CRC exhibit many side effects, hence, it is an urgent need to design effective therapies to prevent and treat CRC. Lactic acid bacteria (LAB) can regulate gut microbiota, intestinal immunity, and intestinal mechanical barrier, which is becoming a hot product for the prevention and treatment of CRC, whereas comprehensive reviews of their anti-CRC mechanisms are limited. This review systematically reveals the latest incidence, mortality, risk factors, and molecular mechanisms of CRC, then summarizes the roles of probiotics in alleviating CRC in animal and clinical studies and critically reviews the possible mechanisms by which these interventions exert their activities. It then shows the limitations in mechanisms and clinical studies, and the suggestions for future research are also put forward, which will play an important role in guiding and promoting the basic and clinical research of remising CRC by LAB and the development of LAB products.

Impact of nisin on Clostridioides difficile and microbiota composition in a faecal fermentation model of the human colon.

AIMS: Nisin is a bacteriocin with a broad spectrum of activity against Gram-positive bacteria. The aims were to assess nisin activity against Clostridioides difficile in a complex microbial environment and determine the minimum inhibitory concentration at which C. difficile growth is suppressed whilst having minimal impact on the faecal microbiota. METHODS AND RESULTS: Faecal slurries were prepared from fresh faecal samples and spiked with C. difficile (106  CFU per ml). Nisin was added to each fermentation at a range of concentrations from 0 to 500 µM. Following 24 h, 16S rRNA gene sequencing was performed, and the presence of viable C. difficile was assessed. There was no viable C. difficile detected in the presence of 50-500 µM nisin. There was a decrease in the diversity of the microbiota in a nisin dose-dependent manner. Nisin predominantly depleted the relative abundance of the Gram-positive bacteria whilst the relative abundance of Gram-negative bacteria such as Escherichia Shigella and Bacteroides increased. CONCLUSIONS: Using an ex vivo model of the colon, this study demonstrates the ability of purified nisin to selectively deplete C. difficile in a faecal microbial environment and establishes the minimum concentration at which this occurs whilst having a minimal impact on the composition of the microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: This study opens up the potential to use nisin as a therapeutic for clostridial gut infections.