Causal effects of gut microbiome on HIV infection: a two-sample mendelian randomization analysis.

BACKGROUND: The causal association between gut microbiome and HIV infection remains to be elucidated. We conducted a two-sample mendelian randomization analysis to estimate the causality between gut microbiome and HIV infection. METHODS: Publicly released genome-wide association studies summary data were collected to perform the mendelian analysis. The GWAS summary data of gut microbiome was retrieved from the MiBioGen consortium, which contains 18 340 samples from 24 cohorts. GWAS summary data of HIV infection was collected from the R5 release of FinnGen consortium, including 357 HIV infected cases and 218 435 controls. The SNPs were selected as instrumental variables according to our selection rules. And SNPs with a F-statistics less than ten were regarded as weak instrumental variables and excluded. Mendelian randomization analysis was conducted by five methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. The Cochran's Q test and MR-Egger intercept test were performed to identify heterogeneity and pleiotropy. Leave-one-out analysis were used to test the sensitivity of the results. RESULTS: Fifteen gut microbiota taxa showed causal effects on HIV infection according to the MR methods. Four taxa were observed to increase the risk of HIV infection, including Ruminococcaceae (OR: 2.468[1.043, 5.842], P: 0.039), Ruminococcaceae UCG005 (OR: 2.051[1.048, 4.011], P: 0.036), Subdoligranulum (OR: 3.957[1.762, 8.887], P < 0.001) and Victivallis (OR: 1.605[1.012, 2.547], P=0.044). Erysipelotrichaceae was protective factor of HIV infection (OR: 0.278[0.106, 0.731], P < 0.001) and Methanobrevibacter was also found to be associated with reduced risk of HIV infection (OR: 0.509[0.265, 0.980], P=0.043). Horizontal pleiotropy was found for Fusicatenibacter (P<0.05) according to the MR-Egger regression intercept analysis. No heterogeneity was detected. CONCLUSION: Our results demonstrate significant causal effects of gut microbiome on HIV infection. These findings facilitate future studies to develop better strategies for HIV prophylaxis through gut microbiome regulation. Further explorations are also warranted to dissect the mechanism of how gut microbiome affects HIV susceptibility.

Molecular-Weight-Dependent Degradation of Plastics: Deciphering Host-Microbiome Synergy Biodegradation of High-Purity Polypropylene Microplastics by Mealworms.

The biodegradation of polypropylene (PP), a highly persistent nonhydrolyzable polymer, by Tenebrio molitor has been confirmed using commercial PP microplastics (MPs) (Mn 26.59 and Mw 187.12 kDa). This confirmation was based on the reduction of the PP mass, change in molecular weight (MW), and a positive Δδ13C in the residual PP. A MW-dependent biodegradation mechanism was investigated using five high-purity PP MPs, classified into low (0.83 and 6.20 kDa), medium (50.40 and 108.0 kDa), and high (575.0 kDa) MW categories to access the impact of MW on the depolymerization pattern and associated gene expression of gut bacteria and the larval host. The larvae can depolymerize/biodegrade PP polymers with high MW although the consumption rate and weight losses increased, and survival rates declined with increasing PP MW. This pattern is similar to observations with polystyrene (PS) and polyethylene (PE), i.e., both Mn and Mw decreased after being fed low MW PP, while Mn and/or Mw increased after high MW PP was fed. The gut microbiota exhibited specific bacteria associations, such as Kluyvera sp. and Pediococcus sp. for high MW PP degradation, Acinetobacter sp. for medium MW PP, and Bacillus sp. alongside three other bacteria for low MW PP metabolism. In the host transcriptome, digestive enzymes and plastic degradation-related bacterial enzymes were up-regulated after feeding on PP depending on different MWs. The T. molitor host exhibited both defensive function and degradation capability during the biodegradation of plastics, with high MW PP showing a relatively negative impact on the larvae.

Understanding the Ecological Robustness and Adaptability of the Gut Microbiome in Plastic-Degrading Superworms (Zophobas atratus) in Response to Microplastics and Antibiotics.

Recent discoveries indicate that several insect larvae are capable of ingesting and biodegrading plastics rapidly and symbiotically, but the ecological adaptability of the larval gut microbiome to microplastics (MPs) remains unclear. Here, we described the gut microbiome assemblage and MP biodegradation of superworms (Zophobas atratus larvae) fed MPs of five major petroleum-based polymers (polyethylene, polypropylene, polystyrene, polyvinyl chloride, and polyethylene terephthalate) and antibiotics. The shift of molecular weight distribution, characteristic peaks of C═O, and metabolic intermediates of residual polymers in egested frass proved depolymerization and biodegradation of all MPs tested in the larval intestines, even under antibiotic suppression. Superworms showed a wide adaptation to the digestion of the five polymer MPs. Antibiotic suppression negatively influenced the survival rate and plastic depolymerization patterns. The larval gut microbiomes differed from those fed MPs and antibiotics, indicating that antibiotic supplementation substantially shaped the gut microbiome composition. The larval gut microbiomes fed MPs had higher network complexity and stability than those fed MPs and antibiotics, suggesting that the ecological robustness of the gut microbiomes ensured the functional adaptability of larvae to different MPs. In addition, Mantel's test indicated that the gut microbiome assemblage was obviously related to the polymer type, the plastic degradability, antibiotic stress, and larval survival rate. This finding provided novel insights into the self-adaptation of the gut microbiome of superworms in response to different MPs.

Periodontal pathogen Aggregatibacter actinomycetemcomitans JP2 correlates with colonic leukocytes decrease and gut microbiome imbalance in mice.

AIM: Evidence suggests that translocation of oral pathogens through the oral-gut axis may induce intestinal dysbiosis. This study aimed to evaluate the impact of a highly leukotoxic Aggregatibacter actinomycetemcomitans (Aa) strain on the gut microbiota, intestinal mucosal integrity and immune system in healthy mice. METHODS: Eight-week-old male C57BL6 mice were divided into control (n = 16) and JP2 groups (n = 19), which received intragastric gavage with PBS and with a suspension of Aa JP2 (HK921), respectively, twice a week for 4 weeks. Colonic lamina propria, fecal material, serum, gingival tissues, and mandibles were obtained for analyses of leukocyte populations, inflammatory mediators, mucosal integrity, alveolar bone loss, and gut microbiota. Differences between groups for these parameters were examined by non-parametric tests. RESULTS: The gut microbial richness and the number of colonic macrophages, neutrophils, and monocytes were significantly lower in Aa JP2-infected mice than in controls (p < .05). In contrast, infected animals showed higher abundance of Clostridiaceae, Lactobacillus taiwanensis, Helicobacter rodentium, higher levels of IL-6 expression in colonic tissues, and higher splenic MPO activity than controls (p < .05). No differences in tight junction expression, serum endotoxin levels, and colonic inflammatory cytokines were observed between groups. Infected animals presented also slightly more alveolar bone loss and gingival IL-6 levels than controls (p < .05). CONCLUSION: Based on this model, intragastric administration of Aa JP2 is associated with changes in the gut ecosystem of healthy hosts, characterized by less live/recruited myeloid cells, enrichment of the gut microbiota with pathobionts and decrease in commensals. Negligible levels of colonic pro-inflammatory cytokines, and no signs of mucosal barrier disruption were related to these changes.

Reference gene catalog and metagenome-assembled genomes from the gut microbiome reveal the microbial composition, antibiotic resistome, and adaptability of a lignocellulose diet in the giant panda.

The giant panda, a strict herbivore that feeds on bamboo, still retains a typical carnivorous digestive system. Reference catalogs of microbial genes and genomes are lacking, largely limiting the antibiotic resistome and functional exploration of the giant panda gut microbiome. Here, we integrated 177 fecal metagenomes of captive and wild giant pandas to construct a giant panda integrated gene catalog (GPIGC) comprised of approximately 4.5 million non-redundant genes and reconstruct 393 metagenome-assembled genomes (MAGs). Taxonomic and functional characterization of genes revealed that the captivity of the giant panda significantly changed the core microbial composition and the distribution of microbial genes. Higher abundance and prevalence of antibiotic resistance genes (ARGs) were detected in the guts of captive giant pandas, and ARG distribution was influenced by geography, for both captive and wild individuals. Escherichia, as the prevalent genus in the guts of captive giant pandas, was the main carrier of ARGs, meaning there is a high risk of ARG transmission by Escherichia. We also found that multiple mcr gene variants, conferring plasmid-mediated mobile colistin resistance, were widespread in the guts of captive and wild giant pandas. There were low proportions of carbohydrate-active enzyme (CAZyme) genes in GPIGC and MAGs compared with several omnivorous and herbivorous mammals. Many members of Clostridium MAGs were significantly enriched in the guts of adult, old and wild giant pandas. The genomes of isolates and MAGs of Clostridiaceae harbored key genes or enzymes in complete pathways for degrading lignocellulose and producing short-chain fatty acids (SCFAs), indicating the potential of these bacteria to utilize the low-nutrient bamboo diet. Overall, our data presented an exhaustive reference gene catalog and MAGs in giant panda gut and provided a comprehensive understanding of the antibiotic resistome and microbial adaptability for a high-lignocellulose diet.

Exploring the causal relationship between periodontitis and gut microbiome: Unveiling the oral-gut and gut-oral axes through bidirectional Mendelian randomization.

AIM: This Mendelian randomization (MR) study was performed to explore the potential bidirectional causal relationship between the gut microbiome (GM) and periodontitis. MATERIALS AND METHODS: We used genetic instruments from the genome-wide association study of European descent for periodontitis from the GeneLifestyle Interactions in Dental Endpoints (GLIDE) consortium (17,353 cases and 28,210 controls) and the FinnGen consortium (4434 cases and 259,234 controls) to investigate the causal relationship with GM (the MiBioGen consortium, 18,340 samples), and vice versa. Several MR techniques, which include inverse variance weighting (IVW), MR-Egger, weighted median, simple mode and weighted mode approaches, were employed to investigate the causal relationship between the exposures and the outcomes. Cochran's Q-test was performed to detect heterogeneity. The MR-Egger regression intercept and MR pleiotropy residual sum and outlier test (MR-PRESSO) were conducted to test potential horizontal pleiotropy. Leave-one-out sensitivity analyses were used to assess the stabilities of single nucleotide polymorphisms (SNPs). Finally, the IVW results from the two databases were analysed using meta-analysis. RESULTS: We confirmed three potential causal relationships between GM taxa and periodontitis at the genus level. Among them, the genera Alistipes and Holdemanella were genetically associated with an increased risk of periodontitis. In reverse, periodontitis may lead to a decreased abundance of the genus Ruminococcaceae UCG014. CONCLUSIONS: The demonstration of a causal link between GM and periodontitis provides compelling evidence, highlighting the interconnectivity and interdependence of the gut-oral and oral-gut axes.

Attenuation of inflammatory bowel disease by oral administration of mucoadhesive polydopamine-coated yeast ß-glucan via ROS scavenging and gut microbiota regulation.

Treatment for inflammatory bowel disease (IBD) is challenging since current anti-inflammatory and immunosuppressive therapies do not address the underlying causes of the illness, which include increased levels of reactive oxygen species (ROS) and dysbiosis of the gut commensal microbiota. Additionally, these treatments often have systemic off-target effects and adverse side effects. In this study, we have developed a prebiotic yeast ß-glucan nanocomplex coated with bio-adhesive polydopamine (YBNs@PDA) to effectively prolong their retention time in the gastrointestinal (GI) tract. The oral administration of YBNs@PDA restored the epithelium barriers, reduced ROS levels, and minimized systemic drug exposure while improved therapeutic efficacy in an acute colitis mouse model. Furthermore, 16S ribosomal RNA genes sequencing demonstrated a higher richness and diversity in gut microflora composition following the treatments. In particular, YBNs@PDA markedly augmented the abundance of Lachnospiraceae NK4A136 and Bifidobacterium, both of which are probiotics with crucial roles in relieving colitis via retaining gut homeostasis. Cumulatively, these results demonstrate that the potential of YBNs@PDA as a novel drug-free, ROS-scavenging and gut microbiota regulation nanoplatform for the treatment of GI disorders.

Analysis of the gut microbiome associated to PVC biodegradation in yellow mealworms.

The potential of invertebrates in the biodegradation of plastic polymers such as polyvinyl chloride (PVC) is receiving increasing attention. The present study is aimed to identify the gut microbiome involved in this degradation in yellow mealworms, i.e., the larvae of Tenebrio molitor Linnaeus. The egested PVC polymer experienced a dramatic reduction in both number average molecular weight (Mn) and weight average molecular weight (Mw) of 99.3% and 99.6%, respectively, whereas FTIR analysis revealed chemical alterations. Mass spectrometry analysis identified two potential degradation products: phthalic acid, di(2-propylpentyl) ester and 2-Propenoic acid, tridecyl ester. Further, we used metagenomic sequencing to elucidate the response of the gut microbiome when transitioning from bran to PVC as a food source, identifying four microorganisms actively involved in PVC degradation. Additionally, metagenomic functional analysis of the gut microbiome identified 111 key gene modules that were significantly enriched. In summary, our findings suggest that yellow mealworms adapt to PVC degradation by modifying their gut microbiome both structurally and functionally.

Analysis of Oral and Gut Microbiome Composition and Its Impact in Patients with Oral Squamous Cell Carcinoma.

The impact of gut and oral microbiota on the clinical outcomes of patients with oral squamous cell carcinoma (OSCC) is unknown. We compared the bacterial composition of dental plaque and feces between patients with OSCC and healthy controls (HCs). Fecal and dental plaque samples were collected from 7 HCs and 18 patients with OSCC before treatment initiation. Terminal restriction fragment-length polymorphism analysis of 16S rRNA genes was performed. Differences in bacterial diversity between the HC and OSCC groups were examined. We compared the occupancy of each bacterial species in samples taken from patients with OSCC and HCs and analyzed the correlation between PD-L1 expression in the tumor specimens and the occupancy of each bacterial species. The gut and oral microbiota of patients with OSCC were more varied than those of HCs. Porphyromonas and Prevotella were significantly more abundant in patients with OSCC than in HCs. The abundance of Clostridium subcluster XIVa in the gut microbiota of the PD-L1-positive group was significantly greater than that in the PD-L1-negative group. The oral and gut microbiomes of patients with OSCC were in a state of dysbiosis. Our results suggest the possibility of new cancer therapies targeting these disease-specific microbiomes using probiotics and synbiotics.

Prophylactic effects of Tibetan goat kefir on depression-like behaviors in chronic unpredictable stress model through the gut-brain axis.

BACKGROUND: Depression is a common psychological disorder, and traditional therapeutic drugs often result in side effects such as emesis, dry mouth, headache, dysentery and constipation. Probiotics and goat milk have garnered widespread attention for their ability to modulate immune function and regulate the endocrine system, and for their anti-inflammatory effects. In this work, the effects of Tibetan goat kefir on the behavior, immune status, neuroendocrine response and gut microbiological composition of chronic unpredictable mild stress (CUMS) mouse models were evaluated. RESULTS: The results indicated that Tibetan kefir goat milk significantly alleviated behavioral despair in mice. Furthermore, the results demonstrated that Tibetan kefir goat milk mitigated the inflammatory response in the mice and moderated the hyperactivity of the hypothalamic-pituitary-adrenal axis and the expression of brain-derived neurotrophic factor. Meanwhile, chronic stress-induced gut microbial abnormalities were restored. In addition, the correlation between gut microbiota and nervous system was evaluated. CONCLUSION: These results explained the potential mechanism of Tibetan kefir in the antidepressant effect on the CUMS model and enriched diets for depressed patients. © 2024 Society of Chemical Industry.

Co-diet supplementation of low density polyethylene and honeybee wax did not influence the core gut bacteria and associated enzymes of Galleria mellonella larvae (Lepidoptera: Pyralidae).

The current plastic pollution throughout the world is a rising concern that demands the optimization of biodegradation processes. One avenue for this is to identify plastic-degrading bacteria and associated enzymes from the gut bacteria of insect models such as Tenebrio molitor, Plodia interpunctella or Galleria mellonella that have the ability to ingest and rapidly degrade polyethylene. Therefore, this study takes part in understanding the role of the gut bacteria by investigating G. mellonella as a biological model feeding with a diet based on honeybee wax mixed or not with low-density polyethylene. Gut microbiome was analyzed by high throughput 16S rRNA sequencing, and Enterococcaceae and Oxalobacteraceae were found to be the major bacterial families. Compared to the control, the supplementation of low-density polyethylene did not cause significant modification of the bacterial microbiota at community and taxa levels, suggesting bacterial microbiome resilience. The bacterial proteome analysis of gut contents was encouraging for the identification of plastic degrading enzymes such as the phenylacetaldehyde dehydrogenase which participate in styrene degradation. This study allowed a better characterization of the gut bacteria of G. mellonella and provided a basis for the further study of biodegradation of polyethylene based on the bacterial microbiota from insect guts.

The forgotten impacts of plastic contamination on terrestrial micro- and mesofauna: A call for research.

Microplastics (MP) and nanoplastics (NP) contamination of the terrestrial environment is a growing concern worldwide and is thought to impact soil biota, particularly the micro and mesofauna community, by various processes that may contribute to global change in terrestrial systems. Soils act as a long-term sink for MP, accumulating these contaminants and increasing their adverse impacts on soil ecosystems. Consequently, the whole terrestrial ecosystem is impacted by microplastic pollution, which also threatens human health by their potential transfer to the soil food web. In general, the ingestion of MP in different concentrations by soil micro and mesofauna can adversely affect their development and reproduction, impacting terrestrial ecosystems. MP in soil moves horizontally and vertically because of the movement of soil organisms and the disturbance caused by plants. However, the effects of MP on terrestrial micro-and mesofauna are largely overlooked. Here, we give the most recent information on the forgotten impacts of MP contamination of soil on microfauna and mesofauna communities (protists, tardigrades, soil rotifers, nematodes, collembola and mites). More than 50 studies focused on the impact of MP on these organisms between 1990 and 2022 have been reviewed. In general, plastic pollution does not directly affect the survival of organisms, except under co-contaminated plastics that can increase adverse effects (e.g. tire-tread particles on springtails). Besides, they can have adverse effects at oxidative stress and reduced reproduction (protists, nematodes, potworms, springtails or mites). It was observed that micro and mesofauna could act as passive plastic transporters, as shown for springtails or mites. Finally, this review discusses how soil micro- and mesofauna play a key role in facilitating the (bio-)degradation and movement of MP and NP through soil systems and, therefore, the potential transfer to soil depths. More research should be focused on plastic mixtures, community level and long-term experiments.

A Reciprocal Link between Oral, Gut Microbiota during Periodontitis: The Potential Role of Probiotics in Reducing Dysbiosis-Induced Inflammation.

Human body is colonized by a florid microbial community of bacteria, archaea, fungi, protists, helminths, and viruses, known as microbiota, which co-evolves with the host and influences its health through all stages of its life. It is well known that oral microorganisms form highly structurally and functionally organized multi-species biofilms and establish a network of complex mutual inter-species interactions having a primary function in synergy, signaling, or antagonism. This ecological model allows the microorganisms to increase their resistance to antimicrobial agents and settle a balanced microbes-host symbiotic relationship that ensures oral and global health status in humans. The host-associated microbiome is an important factor in human health and disease. Therefore, to develop novel diagnostic, therapeutic, and preventive strategies, microbiome's functions and the reciprocal interactions every microbiome entertains with other microbial communities in the human body are being investigated. This review provides an analysis of the literature about the close connection between the two largest microbial communities in humans: the oral and the gut microbiomes. Furthermore, it focuses on how the alteration of their microbial and functional characteristics can lead to and reciprocally influence the onset of both oral and intestinal microbiome-associated illness, along with the potential role of probiotics in ameliorating inflammation and microbial dysbiosis.

Rifaximin-α reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial.

BACKGROUND & AIMS: Rifaximin-α is efficacious for the prevention of recurrent hepatic encephalopathy (HE), but its mechanism of action remains unclear. We postulated that rifaximin-α reduces gut microbiota-derived endotoxemia and systemic inflammation, a known driver of HE. METHODS: In a placebo-controlled, double-blind, mechanistic study, 38 patients with cirrhosis and HE were randomised 1:1 to receive either rifaximin-α (550 mg BID) or placebo for 90 days. PRIMARY OUTCOME: 50% reduction in neutrophil oxidative burst (OB) at 30 days. SECONDARY OUTCOMES: changes in psychometric hepatic encephalopathy score (PHES) and neurocognitive functioning, shotgun metagenomic sequencing of saliva and faeces, plasma and faecal metabolic profiling, whole blood bacterial DNA quantification, neutrophil toll-like receptor (TLR)-2/4/9 expression and plasma/faecal cytokine analysis. RESULTS: Patients were well-matched: median MELD (11 rifaximin-α vs. 10 placebo). Rifaximin-α did not lead to a 50% reduction in spontaneous neutrophil OB at 30 days compared to baseline (p = 0.48). However, HE grade normalised (p = 0.014) and PHES improved (p = 0.009) after 30 days on rifaximin-α. Rifaximin-α reduced circulating neutrophil TLR-4 expression on day 30 (p = 0.021) and plasma tumour necrosis factor-α (TNF-α) (p <0.001). Rifaximin-α suppressed oralisation of the gut, reducing levels of mucin-degrading sialidase-rich species, Streptococcus spp, Veillonella atypica and parvula, Akkermansia and Hungatella. Rifaximin-α promoted a TNF-α- and interleukin-17E-enriched intestinal microenvironment, augmenting antibacterial responses to invading pathobionts and promoting gut barrier repair. Those on rifaximin-α were less likely to develop infection (odds ratio 0.21; 95% CI 0.05-0.96). CONCLUSION: Rifaximin-α led to resolution of overt and covert HE, reduced the likelihood of infection, reduced oralisation of the gut and attenuated systemic inflammation. Rifaximin-α plays a role in gut barrier repair, which could be the mechanism by which it ameliorates bacterial translocation and systemic endotoxemia in cirrhosis. CLINICAL TRIAL NUMBER: ClinicalTrials.gov NCT02019784. LAY SUMMARY: In this clinical trial, we examined the underlying mechanism of action of an antibiotic called rifaximin-α which has been shown to be an effective treatment for a complication of chronic liver disease which effects the brain (termed encephalopathy). We show that rifaximin-α suppresses gut bacteria that translocate from the mouth to the intestine and cause the intestinal wall to become leaky by breaking down the protective mucus barrier. This suppression resolves encephalopathy and reduces inflammation in the blood, preventing the development of infection.

Influence of Polymer Size on Polystyrene Biodegradation in Mealworms (Tenebrio molitor): Responses of Depolymerization Pattern, Gut Microbiome, and Metabolome to Polymers with Low to Ultrahigh Molecular Weight.

Biodegradation of polystyrene (PS) in mealworms (Tenebrio molitor lavae) has been identified with commercial PS foams. However, there is currently limited understanding of the influence of molecular weight (MW) on insect-mediated plastic biodegradation and the corresponding responses of mealworms. In this study, we provided the results of PS biodegradation, gut microbiome, and metabolome by feeding mealworms with high-purity PS microplastics with a wide variety of MW. Over 24 days, mealworms (50 individuals) fed with 0.20 g of PS showed decreasing removal of 74.1 ± 1.7, 64.1 ± 1.6, 64.4 ± 4.0, 73.5 ± 0.9, 60.6 ± 2.6, and 39.7 ± 4.3% for PS polymers with respective weight-average molecular weights (Mw) of 6.70, 29.17, 88.63, 192.9, 612.2, and 1346 kDa. The mealworms degraded most PS polymers via broad depolymerization but ultrahigh-MW PS via limited-extent depolymerization. The gut microbiome was strongly associated with biodegradation, but that with low- and medium-MW PS was significantly distinct from that with ultrahigh-MW PS. Metabolomic analysis indicated that PS biodegradation reprogrammed the metabolome and caused intestinal dysbiosis depending on MW. Our findings demonstrate that mealworms alter their gut microbiome and intestinal metabolic pathways in response to in vivo biodegradation of PS polymers of various MWs.

Oral pathogen in the pathogenesis of colorectal cancer.

The human body contains more than 100 trillion microorganisms, including the oral cavity, the skin, and the gastrointestinal tract. After the gastrointestinal tract, the oral cavity harbors one of the most diverse microbial communities within the human body and harbors more than 770 species of bacteria. The composition of the oral and gut microbiomes is quite different, but there may be a microbiological link between the two mucosal sites during the course of disease. More studies indicate that oral bacteria can disseminate to the distal gut via enteral or hematogenous routes. This is mostly obvious in periodontitis, where specific bacteria, such as Fusobacterium nucleatum and Porphyromonas gingivalis, show this pathogenic feature. The translocation of oral microbes to the gut may give rise to a variety of gastrointestinal diseases, including colorectal cancer. However, the precise role that oral microbe play in colorectal cancer has not been fully illustrated. Here, we summarize the current researches on possible pathways of ectopic gut colonization by oral bacteria and their possible contribution to the pathogenesis of colorectal cancer. Understanding the correlation of the oral-to-gut microbial axis in the pathogenesis of colorectal cancer will contribute to precise diagnosis and effective treatment.

Community and shotgun metagenomic analysis of Alligator mississippiensis oral cavity and GI tracts reveal complex ecosystems and potential reservoirs of antibiotic resistance.

We report here the community structure and functional analysis of the microbiome of the Alligator mississippiensis GI tract from the oral cavity through the entirety of the digestive tract. Although many vertebrate microbiomes have been studied in recent years, the archosaur microbiome has only been given cursory attention. In the oral cavity we used amplicon-based community analysis to examine the structure of the oral microbiome during alligator development. We found a community that diversified over time and showed many of the hallmarks we would expect of a stable oral community. This is a bit surprising given the rapid turnover of alligator teeth but suggests that the stable gumline microbes are able to rapidly colonize the emerging teeth. As we move down the digestive tract, we were able to use both long and short read sequencing approaches to evaluate the community using a shotgun metagenomics approach. Long read sequencing was applied to samples from the stomach/duodenum, and the colorectal region, revealing a fairly uniform and low complexity community made up primarily of proteobacteria at the top of the gut and much more diversity in the colon. We used deep short read sequencing to further interrogate this colorectal community. The two sequencing approaches were concordant with respect to community structure but substantially more detail was available in the short read data, in spite of high levels of host DNA contamination. Using both approaches we were able to show that the colorectal community is a potential reservoir for antibiotic resistance, human pathogens such as Clostridiodes difficile and a possible source of novel antimicrobials or other useful secondary metabolites.

Polystyrene bead ingestion promotes adiposity and cardiometabolic disease in mice.

Vast amounts of plastic materials are produced in the modern world and despite recycling efforts, large amounts are disposed in water systems and landfills. Under these storage conditions, physical weathering and photochemical processes break down these materials into smaller particles of the micro- and nano-scale. In addition, ecosystems can be contaminated with plastic particles which are manufactured in these size ranges for commercial purposes. Independent of source, microplastics are abundant in the environment and have found their way into water supplies and the food cycle where human exposure is inevitable. Nevertheless, the health consequences of microplastic ingestion, inhalation, or absorption are largely unknown. In this study we sought to determine if ingestion of microplastics promoted pre-clinical cardiovascular disease (CVD). To do this, we supplied mice with normal drinking water or that supplemented with polystyrene beads of two different sizes (0.5 µm and 5 µm) and two different doses (0.1 µg/ml and 1 µg/ml) each for 12 weeks and measured several indices of metabolism and glucose homeostasis. As early as 3 weeks of consumption, we observed an accelerated weight gain with a corresponding increase in body fat for some exposure groups versus the control mice. Some exposure groups demonstrated increased levels of fasting plasma glucose. Those mice consuming the smaller sized beads (0.5 µm) at the higher dose (1 µg/ml), had increased levels of fasting plasma insulin and higher homeostatic model assessment of insulin resistance (HOMA-IR) scores as well. This was accompanied by changes in the gut microbiome consistent with an obese phenotype. Using samples of perivascular adipose tissue collected from the same group, we observed changes in gene expression consistent with increased adipogenesis. These results suggest that ingestion of polystyrene beads promotes a cardiometabolic disease phenotype and thus may be an unrecognized risk factor for CVD.

Methotrexate promotes recovery of arthritis-induced alveolar bone loss and modifies the composition of the oral-gut microbiota.

OBJECTIVES: The impact of rheumatoid arthritis (RA) on the shaping of the oral and gut microbiome raises the question of whether and how RA treatment modifies microbial communities. We examined changes in the oral and gut microbiota in a mouse model of antigen-induced arthritis (AIA) treated or not with methotrexate (MTX). METHODS: Maxillae and stools were evaluated by the MiSeq platform of the V4 region of the 16S rRNA gene. Alveolar bone parameters were analysed by micro-computed tomography. Moreover, arthritis-induced changes in hyperalgesia and oedema were assessed, along with the impact on periodontal bone health. RESULTS: Microbial communities in MTX-treated AIA mice revealed distinct clusters compared to the control and AIA groups. Overall, MTX impacted the richness and variability of microorganisms in the oral-gut axis microbiome at the phylum level. Regarding the oral microbiome, while in the control group the most dominant phylum was Firmicutes, in the AIA group there was a shift towards the predominance of Campilobacteriota and Bacteroidetes associated with the disease. MTX treatment led to greater dominance of the health-associated phylum Proteobacteria. In the gut microbiome, AIA induction resulted in increased abundance of the Verrucomicrobiota phylum, and MTX treatment restored its levels compared to control. Importantly, the MTX-treated AIA animals had significantly less periodontal bone loss, as well as decreased hyperalgesia and joint oedema compared to the AIA animals. CONCLUSION: Data suggest the benefit of MTX treatment in protecting alveolar bone, in addition to providing new insights on the drug-microbiome interaction in the course of RA.

The Relationship of Tumor Microbiome and Oral Bacteria and Intestinal Dysbiosis in Canine Mammary Tumor.

Canine mammary tumor (CMT) is the most common tumor in dogs, with 50% of malignant cases, and lacks an effective therapeutic schedule, hence its early diagnosis is of great importance to achieve a good prognosis. Microbiota is believed to play important roles in systemic diseases, including cancers. In this study, 91 tumors, 21 oral and fecal samples in total were collected from dogs with CMTs, and 31 oral and 21 fecal samples from healthy dogs were collected as control. The intratumoral, oral and gut bacterial community of dogs with CMTs and healthy dogs was profiled by 16S rRNA high-throughput sequencing and bioinformatic methods. The predominant intratumoral microbes were Ralstonia, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, Pseudomonas, unidentified_Chloroplast and Bacteroides at the genus level. In addition, our findings demonstrated striking changes in the composition of the oral and gut bacterium community in the dogs suffered from CMTs compared to the healthy dogs, with a significant increase of Bacteroides which also was the significant microbial biomarker in the oral and gut bacterium community. It showed that the Bacteroides was shared in the intratumoral, oral and intestinal bacterial microbiomes, confirming that microbiota might travel from the mouth to the intestine and finally to the distant mammary tumor tissue. This study provides a new microbiological idea for the treatment of canine mammary tumors, and also provides a theoretical basis for the study of human breast cancer.