Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract

Emerging research supports that triclosan (TCS), an antimicrobial agent found in thousands of consumer products, exacerbates colitis and colitis-associated colorectal tumorigenesis in animal models. While the intestinal toxicities of TCS require the presence of gut microbiota, the molecular mechanisms involved have not been defined. Here we show that intestinal commensal microbes mediate metabolic activation of TCS in the colon and drive its gut toxicology. Using a range of in vitro, ex vivo, and in vivo approaches, we identify specific microbial β-glucuronidase (GUS) enzymes involved and pinpoint molecular motifs required to metabolically activate TCS in the gut. Finally, we show that targeted inhibition of bacterial GUS enzymes abolishes the colitis-promoting effects of TCS, supporting an essential role of specific microbial proteins in TCS toxicity. Together, our results define a mechanism by which intestinal microbes contribute to the metabolic activation and gut toxicity of TCS, and highlight the importance of considering the contributions of the gut microbiota in evaluating the toxic potential of environmental chemicals.

First Report of Fecal Microflora of Wild Bar-Headed Goose in Tibet Plateau

The bar-headed goose (Anser indicus) has two black spots on its head. It is considered an important bird in China. It breeds in plateau lakes, especially saltwater lakes, and swamp areas. However, the intestinal flora of wild bar-headed geese in the Tibet Autonomous Region is currently not known. In this study, 16S rDNA sequencing was performed on the intestinal microbes of wild bar-headed geese. A total of 513,505 reads of raw data were obtained, and the results analyzed the average number of 128,376 ± 2,392 reads per sample. The microbiota of all samples consists of 10 main bacterial phyla, including Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, Cyanobacteria, Patescibacteria, Deferribacteres, Planctomy-cetes, Fusobacteria, and Tenericutes. The results indicated that Firmicutes (67.34%) was the predominant phylum, followed by Proteobacteria (29.03%) and Cyanobacteria (1.97%). In our research, we identified the intestinal flora of the wild bar-headed goose, which provides valuable information for further research on the gene function of the bar-headed goose and the intestinal flora of wild animals. These findings are also useful and valuable for genetic and high-altitude research in the Tibet Autonomous Region.

The Potential Prebiotic Berberine Combined With Methimazole Improved the Therapeutic Effect of Graves’ Disease Patients Through Regulating the Intestinal Microbiome

Graves’ disease, a typical metabolism disorder, causes diffuse goiter accompanied by ocular abnormalities and ocular dysfunction. Although methimazole (MI) is a commonly used drug for the treatment of GD, the efficacy of methimazole is only limited to the control of clinical indicators, and the side effects of MI should be seriously considered. Here, we designed a 6-month clinical trial that divided the patients into two groups: a methimazole group (n=8) and a methimazole combined with potential prebiotic berberine group (n=10). The effects of both treatments on thyroid function and treatment outcomes in patients with GD were assessed by thyroid index measurements and gut microbiota metagenomic sequencing. The results showed that the addition of berberine restored the patients’ TSH and FT3 indices to normal levels, whereas MI alone restored only FT3. In addition, TRAb was closer to the healthy threshold at the end of treatment with the drug combination. MI alone failed to modulate the gut microbiota of the patients. However, the combination of berberine with methimazole significantly altered the microbiota structure of the patients, increasing the abundance of the beneficial bacteria Lactococcus lactis while decreasing the abundance of the pathogenic bacteria Enterobacter hormaechei and Chryseobacterium indologenes. Furthermore, further mechanistic exploration showed that the addition of berberine resulted in a significant upregulation of the synthesis of enterobactin, which may have increased iron functioning and thus restored thyroid function. In conclusion, methimazole combined with berberine has better efficacy in patients with GD, suggesting the potential benefit of berberine combined with methimazole in modulating the composition of intestinal microbes in the treatment of GD, providing new strong evidence for the effectiveness of combining Chinese and Western drugs from the perspective of modulating the intestinal microbiota.

Comparison and Analysis of Gut Microbiota in Children With IgA Vasculitis With Different Clinical Symptoms

Background: Henoch-Schönlein purpura, now called immunoglobulin A (IgA) vasculitis, is a common autoimmune disease in children, its association with gut microbiota composition remains unknown.Methods: The collected cases were divided into three groups: G1 group of simple skin type, G2 group with no digestive tract expression, G3 group of mixed digestive tract, and C group of healthy children. The fecal samples of each group of children were collected and the sequencing data was processed and analyzed. The dilution curve reflected the reasonableness of the amount of sequencing data.Results: The number of species composition sequences in the G1, G2 and G3 groups was lower than that in the C group, especially for the G2 and G3 groups. The four most abundant bacteria were Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria. The relative abundance of Proteobacteria in the G2 and G3 groups was significantly higher than that in the G1 and C groups, while the relative abundance of Actinobacteria was significantly reduced, and the relative abundance of Actinobacteria in the G1 group was lower than that in the C group. Principal component analysis of the UPGMA clustering tree and each group of samples showed that the microbial community composition of the same group of samples was similar.Conclusions: The abundance of intestinal microbes in children with IgA vasculitis is lower than in normal children. Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria are the four most abundant bacteria in the intestinal flora of children. Proteobacteria and Actinobacteria are associated with organ involvement in IgA vasculitis.

Alterations in intestinal microbiota composition coincide with impaired intestinal morphology and dysfunctional ileal immune response in growing-finishing pigs under constant chronic heat stress

Background Previous studies had shown that short-term acute heat stress (HS) affected the host’s metabolism and intestinal microbiota independent of feed intake (FI) reduction, and long-term calorie restriction caused intestinal morphological injuries and gut microbial alterations. However, research on the effects of constant chronic HS on intestinal microbial composition and the roles of FI reduction played in is limited. This study aimed to investigate the effects of 7-day constant chronic HS on the composition of intestinal microbes in growing-finishing pigs, and its relationship with pigs’ performance, intestinal morphology, and ileal immune response. Twenty-four growing-finishing pigs (Duroc × Large White × Landrace, 30 ± 1 kg body weight) were randomly assigned to three treatments (n = 8), 1) thermal neutral (TN) conditions (25 ± 1 °C) with ad libitum FI, 2) HS conditions (35 ± 1 °C) with ad libitum FI, 3) pair-fed (PF) with HS under TN conditions to discriminate the confounding effects of dissimilar FI, and the FI was the previous day’s average FI of HS. The small intestinal segments (duodenum, jejunum, and ileum) and feces were collected on d 8. Results Results indicated that HS drastically declined (P < 0.05) average daily gain (ADG) and average daily feed intake (ADFI) (about 61%) in comparison with TN, and caused hyperpyrexia, meanwhile PF caused hypothermia. Morphological observation by light and electron microscopes showed that both HS and PF treatment decreased (P < 0.05) the villus and microvillus height compared with TN. Additionally, HS increased (P < 0.05) protein expression of heat shock protein 70 in the duodenum, jejunum, and ileum. Furthermore, the expression of tight junction protein zonula occluden-1 (ZO-1) in the duodenum and ileum, and Occludin in the ileum were enhanced (P < 0.05) compared with TN and PF. Moreover, HS significantly enhanced (P < 0.05) the mRNA relative expression of inflammatory cytokines (TLR-2, TLR-4, and tumor necrosis factor-α (TNF-α), IL-6, IL-8, PG1–5, β-defensin 2 (pBD-2)), mucins (mucin-1 and mucin-2) and P65 protein level in the ileal mucosa tissue. Intestinal microbiota analysis by 16S rRNA sequencing showed lower (P < 0.10) α diversity in both HS and PF, and a separated cluster of β diversity among groups. Compared with TN, HS but not PF mainly reduced (FDR < 0.05) Bacteroidetes (phylum), Bacteroidia (class) and elevated the proportions of Proteobacteria (phylum, FDR < 0.05), Bacillales (order, FDR < 0.05), Planococcaceae (family, FDR < 0.05), Kurthia (genus, FDR < 0.05), Streptococcaceae (family, FDR < 0.10) and Streptococcus (genus, FDR < 0.10). Notably, Lactobacillales (order) was decreased (FDR < 0.05) by PF alone. Furthermore, the Spearman correlation analysis indicated that the microbes prevalent in HS were positively (P < 0.05) associated with intestinal morphological injuries indicators and ileal immune response parameters, and the microbes reduced in HS were negatively (P < 0.05) with the performance data. Conclusions Intestinal morphological injuries and ileal immune response caused by constant chronic HS independent of FI showed close connections with alterations in intestinal microbiota in growing-finishing pigs.

Role of Vitamin K in Intestinal Health

Intestinal diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancer (CRC) generally characterized by clinical symptoms, including malabsorption, intestinal dysfunction, injury, and microbiome imbalance, as well as certain secondary intestinal disease complications, continue to be serious public health problems worldwide. The role of vitamin K (VK) on intestinal health has drawn growing interest in recent years. In addition to its role in blood coagulation and bone health, several investigations continue to explore the role of VK as an emerging novel biological compound with the potential function of improving intestinal health. This study aims to present a thorough review on the bacterial sources, intestinal absorption, uptake of VK, and VK deficiency in patients with intestinal diseases, with emphasis on the effect of VK supplementation on immunity, anti-inflammation, intestinal microbes and its metabolites, antioxidation, and coagulation, and promoting epithelial development. Besides, VK-dependent proteins (VKDPs) are another crucial mechanism for VK to exert a gastroprotection role for their functions of anti-inflammation, immunomodulation, and anti-tumorigenesis. In summary, published studies preliminarily show that VK presents a beneficial effect on intestinal health and may be used as a therapeutic drug to prevent/treat intestinal diseases, but the specific mechanism of VK in intestinal health has yet to be elucidated.

Treatment of Hyperammonemia by Transplanting a Symbiotic Pair of Intestinal Microbes

Hyperammonemia is a deleterious and inevitable consequence of liver failure. However, no adequate therapeutic agent is available for hyperammonemia. Although recent studies showed that the pharmabiotic approach could be a therapeutic option for hyperammonemia, its development is clogged with poor identification of etiological microbes and low transplantation efficiency of candidate microbes. In this study, we developed a pharmabiotic treatment for hyperammonemia that employs a symbiotic pair of intestinal microbes that are both able to remove ammonia from the surrounding environment. By a radioactive tracing experiment in mice, we elucidated how the removal of ammonia by probiotics in the intestinal lumen leads to lower blood ammonia levels. After determination of the therapeutic mechanism, ammonia-removing probiotic strains were identified by high-throughput screening of gut microbes. The symbiotic partners of ammonia-removing probiotic strains were identified by screening intestinal microbes of a human gut, and the pairs were administrated to hyperammonemic mice to evaluate therapeutic efficacy. Blood ammonia was in a chemical equilibrium relationship with intestinal ammonia. Lactobacillus reuteri JBD400 removed intestinal ammonia to shift the chemical equilibrium to lower the blood ammonia level. L. reuteri JBD400 was successfully transplanted with a symbiotic partner, Streptococcus rubneri JBD420, improving transplantation efficiency 2.3×103 times more compared to the sole transplantation while lowering blood ammonia levels significantly. This work provides new pharmabiotics for the treatment of hyperammonemia as well as explains its therapeutic mechanism. Also, this approach provides a concept of symbiotic pairs approach in the emerging field of pharmabiotics.

Impact of Gut Microbiota on Radiation-Associated Cognitive Dysfunction and Neuroinflammation in Mice

Radiation-induced brain injury is a common complication of brain irradiation that eventually leads to irreversible cognitive impairment. Evidence has shown that the gut microbiome may play an important role in radiation-induced cognitive function. However, the effects of gut microbiota on radiation-induced brain injury (RIBI) remain poorly understood. Here we studied the link between intestinal microbes and radiation-induced brain injury to further investigate the effects of intestinal bacteria on neuroinflammation and cognitive function. We first verified the differences in gut microbes between male and female mice and administered antibiotics to C57BL/6 male mice to deplete the gut flora and then expose mice to radiation. We found that depletion of intestinal flora after irradiation may act as a protective modulator against radiation-induced brain injury. Moreover, we found that pretreatment with depleted gut microbes in RIBI mice suppressed brain pro-inflammatory factor production, and high-throughput sequencing analysis of mouse feces at 1-month postirradiation revealed microbial differences. Interestingly, a proportion of Verrucomicrobia Akkermansia showed partial recovery. Additionally, short-chain fatty acid treatments increased neuroinflammation in the radiation-induced brain injury model. Although a further increase in cognitive function was not observed, brain injury was aggravated in whole-brain irradiated mice to some extent. The protective effects of depleted intestinal flora and the utilization of the brain-gut axis open new avenues for development of innovative therapeutic strategies for radiation-induced brain injury.

Polyphenols—Gut Microbiota Interrelationship: A Transition to a New Generation of Prebiotics

The present review summarizes the studies carried out on this topic in the last five years. According to the new definitions, among all the compounds included in the group of prebiotics, polyphenols are probably the most important secondary metabolites produced by the plant kingdom. Many of these types of polyphenols have low bioavailability, therefore reaching the colon in unaltered form. Once in the colon, these compounds interact with the intestinal microbes bidirectionally by modulating them and, consequently, releasing metabolites. Despite much research on various metabolites, little is known about the chemistry of the metabolic routes used by different bacteria species. In this context, this review aims to investigate the prebiotic effect of polyphenols in preclinical and clinical studies, highlighting that the consumption of polyphenols leads to an increase in beneficial bacteria, as well as an increase in the production of valuable metabolites. In conclusion, there is much evidence in preclinical studies supporting the prebiotic effect of polyphenols, but further clinical studies are needed to investigate this effect in humans.

Developmental Change of Yolk Microbiota and Its Role on Early Colonization of Intestinal Microbiota in Chicken Embryo

Although the fertilized eggs were found to contain microbes in early studies, the detailed composition of yolk microbiota and its influence on embryo intestinal microbiota have not been satisfactorily examined yet. In this study, the yolk microbiota was explored by using 16s rRNA sequencing at different developmental stages of the broiler embryo. The results showed that the relative abundance of yolk microbiota was barely changed during embryogenesis. According to the KEGG analysis, the yolk microbiota were functionally related to amino acid, carbohydrate, and lipid metabolisms during chicken embryogenesis. The yolk microbiota influences the embryonic intestinal microbiota through increasing the colonization of Proteobacteria, Firmicutes, and Bacteroidetes in the intestine, particularly. The intestinal microbes of neonatal chicks showed higher proportions of Faecalibacterium, Blautia, Coprococcus, Dorea, and Roseburia compared to the embryonic intestinal microbiota. Our findings might give a better understanding of the composition and developmental change of yolk microbiota and its roles in shaping the intestinal microbiota.