Host genes regulate the composition and function of gut microbiota, thereby influencing the development of colorectal cancer (CRC). This study aims to investigate the mechanisms by which host gene TRPV4 deficiency exacerbates CRC in mice through remodeling gut microbiota and promoting inflammatory cytokine secretion.

TRPV4 knockout (TRPV4^-/-) mice were used to establish a CRC mouse model induced by dextran sodium sulfate (DSS) and azoxymethane (AOM). Male TRPV4^-/- and wild-type mice (6 to 8 weeks old) were stratified by body weight and randomly divided into TRPV4^-/- group (n=7) and WT group (n=7). The mouse model of CRC was established through a single intraperitoneal injection of 10 mg/kg AOM on day 1 of week 1; from day 7, drinking water containing 1. 5% DSS for 7 consecutive days, followed by 2 weeks of regular water, with this DSS treatment cycle being repeated for 3 times; a second intraperitoneal injection of 10 mg/kg AOM on day 1 of week 6. CRC progression was assessed with tumor number, size, burden, colon length, spleen weight, colonic morphology (HE staining) and pathological score, and immunohistochemical detection of proliferating cell nuclear antigen (PCNA). Additionally, male TRPV4^-/- and wild-type mice (6 to 8 weeks old) were stratified by body weight and randomly divided into antibiotic cocktail (ABX)-TRPV4^-/- group (n=5) and ABX-WT group (n=5). The ABX mixture was used to deplete the gut microbiota to evaluate the microbiota-dependent effects of TRPV4 on CRC. Fecal samples were collected from the TRPV4^-/- group (n=19) and WT group (n=21) before modeling, and then subjected to 16S rRNA sequencing to determine the effect of TRPV4 gene on mouse gut microbiota. RNA sequencing was performed on mouse colonic tissue; Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was used to examine enrichment of differentially expressed genes, and fecal bacteria-cell co-incubation experiments were conducted in vitro.

The TRPV4^-/- group exhibited significantly increased tumor incidence (P=0.0379), tumor burden (P=0.0003), histopathological score (P<0.0001), and PCNA-positive rate (P<0.0001), and shorter colon length (P=0.0012) compared with the WT group. After ABX treatment, no significant differences were observed between the TRPV4^-/- group and WT group in tumor incidence, tumor burden, colon length, histopathological score, or PCNA positive rate (P>0.05). 16S rRNA sequencing demonstrated that TRPV4 deficiency reshaped the gut microbiota structure, with significant differences in β diversity between the TRPV4^-/- and WT groups (P=0.001) and distinct microbiota composition profiles. Colon tissue RNA-seq results revealed 218 significantly upregulated and 152 downregulated genes in TRPV4^-/- mice. KEGG pathway enrichment showed that differentially expressed genes were significantly enriched in cytokine signaling pathways and TNF signaling pathways. In vitro co-incubation results demonstrated that the transcription levels of TNF-α (P<0.0001), IL-1β (P<0.0001), and IL-23 (P<0.0001) were significantly upregulated in TRPV4^-/- microbiota-cell co-cultures.

The gut microecology formed by TRPV4 deficiency may exacerbate CRC by promoting the secretion of inflammation-related cytokines.

Nosocomial infections in patients with severe acute pancreatitis (SAP) are frequently driven by impaired intestinal barrier function, which facilitates bacterial translocation and contributes to adverse clinical outcomes. Saccharomyces boulardii (S. boulardii) can reconstitute gut microbiota composition. We investigated whether S. boulardii combined with enteral nutrition (EN) affects the microbiome and nosocomial infections in SAP.

This study is a single centre, open-label randomized controlled trial. We included 50 patients with SAP in a Chinese gastroenterology intensive care unit (ICU), randomized to Probiotic group (S. boulardii and EN) or the Control group (EN). Throat/oropharyngeal and rectal swabs were collected from patients with SAP on days 0, 1, 3, 6, 9, 12, and 15 of ICU admission. The primary endpoints were nosocomial infection and fungemia, whereas the secondary endpoints were ICU mortality, 28-day mortality, ICU stay, and length of hospital stay. All samples were subjected to full-length 16 s rRNA and internal transcribed spacer (ITS) sequencing. Multivariate analysis was performed using normalized microbial and corresponding clinical data.

After data processing, 213 16S rRNA and 120 ITS samples were analysed. S. boulardii prevented nosocomial infections (0/27 in the Probiotic group vs 5/23 in the Control group; P < 0.05). Intestinal fungi were closely associated with nosocomial infections. Bioinformatic analysis showed that S. boulardii prevented nosocomial infections by reducing intestinal bacterial perturbation and inhibiting the proliferation of Enterococcus in the intestine, and Candida in the respiratory tract and intestines.

S. boulardii in patients with SAP may positively alter the respiratory and intestinal microbiome and decrease the incidence of nosocomial infections.

This study was approved by the Ethics Committee of Xinqiao Hospital, Army Medical University, Chongqing China (2021-yd030–01), which was retrospectively registered at the Chinese Clinical Trial Registry (ChiCTR2200056011, Date of Registration: 30/01/2022 https://www.chictr.org.cn/showproj.html?proj=151215).

To compare the differences in gut microbiota between cirrhosis patients receiving transjugular intrahepatic portosystemic shunt (TIPS) and those not, and explore the relationship between TIPS surgery and gut microbiota in order to provide new ideas for improving the prognosis of cirrhosis patients after TIPS surgery based on gut microbiota.

Those who had received TIPS surgery previously were assigned into the operation group, and those without the surgery served as the control group. Their stool samples were collected for 16S rRNA sequencing, and the correlation between gut microbiota and clinical indicators was analyzed.

There were no significant differences in gender, age, body mass index (BMI), etiology and other baseline data between the 2 groups (P>0.05), but obvious differences were observed in clinical serological indicators between them, including INR, APTT, RBC and PT counts, and HGB, ALP, ALB, total bilirubin (TBIL), and URE levels (P<0.05). No statistical difference in alpha diversity was observed between the operation group and the control group (P>0.05), but beta diversity was obviously different (P<0.01), among which Bacteroides was increased in the operation group (P<0.01)and Bifidobacterium was increased in the control group (P<0.05). The function prediction analysis of gut microbiota showed that the metabolism of D-glutamine and D-glutamate (P<0.05) and biosynthesis with secondary bile acids (P<0.05) were up-regulated in the operation group compared with the control group. Correlation analysis between clinical indicators and flora indicated that TBIL and direct bilirubin (DBIL) were significantly correlated with the metabolic pathways of Bacteroides and Secondary bile acids biosynthesis.

Characteristic changes in gut microbiota are found in cirrhosis patients with and without TIPS surgery. Bacteroides may be involved in the regulation of metabolism of bile acids and thus increase bilirubin level.