Fasting mimicking diet extends lifespan and improves intestinal and cognitive health.

Caloric restriction is an effective means of extending a healthy lifespan. Fasting mimicking diet (FMD) is a growing pattern of caloric restriction. We found that FMD significantly prolonged the lifespan of prematurely aging mice. In naturally aging mice, FMD improved cognitive and intestinal health. Through a series of behavioral experiments, we found that FMD relieved anxiety and enhanced cognition in aged mice. In the intestine, the FMD cycles enhanced the barrier function, reduced senescence markers, and maintained T cell naïve-memory balance in the lamina propria mucosa. To further explore the causes of immune alterations, we examined changes in the stool microbiota using 16S rRNA sequencing. We found that FMD remodeled gut bacterial composition and significantly expanded the abundance of Lactobacillus johnsonii. Our research revealed that FMD has in-depth investigative value as an anti-aging intervention for extending longevity and improving cognition, intestinal function, and gut microbiota composition.

Imbalance of gut microbiota in gestational diabetes.

AIM: To investigate the differences in gut microbiota composition among nonpregnant women of reproductive age, healthy pregnant women, and gestational diabetes (GD) patients. METHODS: A total of 45 outpatients were enrolled and divided into three groups: nonpregnant women of reproductive age (control group, n = 23), healthy pregnant women (normal group, n = 10), and GD patients (GD group, n = 12). Faecal samples were collected and sequenced using 16S rRNA gene sequencing to analyse the microbial composition. RESULTS: (1) Pregnant patients exhibited an increase in the abundance of Streptococcus (Pnormal = 0.01286, PGD = 0.002965) and Blautia (Pnormal = 0.0003924, PGD = 0.000246) but a decrease in the abundance of Roseburia (Pnormal = 0.0361, PGD = 0.007075), Phascolarctobacterium (Pnormal = 0.0003906, PGD = 0.02499) and Lachnoclostridium (Pnormal = 0.0003906, PGD = 0.03866). (2) Compared with healthy pregnant women, GD patients had an excessive increase in Streptococcus abundance and decrease in Roseburia abundance. The increase in Blautia abundance and the decrease in Phascolarctobacterium and Lachnoclostridium abundance in GD patients were less than those in healthy pregnant women. (3) The abundance of Faecalibacterium prausnitzii decreased significantly in GD patients (PGD = 0.02985) but not in healthy pregnant patients (Pnormal = 0.1643). CONCLUSIONS: Abnormal increases and decreases in the abundances of gut microbiota components, especially Faecalibacterium prausnitzii, were observed in GD patients. TRIAL REGISTRATION: The cross-sectional research was conducted in accordance with the Declaration of Helsinki, and approved by Sir Run Run Shaw Hospital Clinical Trials and Biomedical Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR1900026164, 24/09/2019, http://www.chictr.org.cn/showproj.aspx?proj=43,455 ).

Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer.

The immune checkpoint blockade (ICB) response in human cancers is closely linked to the gut microbiota. Here, we report that the abundance of commensal Lactobacillus johnsonii is positively correlated with the responsiveness of ICB. Supplementation with Lactobacillus johnsonii or tryptophan-derived metabolite indole-3-propionic acid (IPA) enhances the efficacy of CD8+ T cell-mediated αPD-1 immunotherapy. Mechanistically, Lactobacillus johnsonii collaborates with Clostridium sporogenes to produce IPA. IPA modulates the stemness program of CD8+ T cells and facilitates the generation of progenitor exhausted CD8+ T cells (Tpex) by increasing H3K27 acetylation at the super-enhancer region of Tcf7. IPA improves ICB responsiveness at the pan-cancer level, including melanoma, breast cancer, and colorectal cancer. Collectively, our findings identify a microbial metabolite-immune regulatory pathway and suggest a potential microbial-based adjuvant approach to improve the responsiveness of immunotherapy.

Examining Incidence of Diabetes in People Living with HIV: Tracking the Shift in Traditional and HIV-related Risk Factors.

BACKGROUND AND OBJECTIVE: The risk factors of diabetes mellitus (DM) in people with HIV (PWH) may be dynamic in a life course manner. This study aimed to describe incidence of DM and investigate the trajectory of changes in risk factor associated with DM incidence over around 15 years among a statewide cohort of PWH in South Carolina (SC). DESIGN: This is a population-based cohort study. METHODS: Data were retrieved from the integrated statewide electronic health records between 2006 and 2020 in SC. Separate subgroup analysis was conducted according to the patients' different follow up duration (i.e., 5, 10, and 15 years) to observe the evolving risk factors of DM development, using multivariable logistic regressions. RESULTS: The DM incidence among a total of 9115 PWH was 8.9 per 1000 person-years. In the overall model, being >60 years old, hypertension, and obesity were positively associated with DM while alcohol consumption, years of HIV diagnosis and high percentage days of viral suppression were negatively associated with the outcome. In the subgroup analyses, similar risk factors were observed. The odds of DM increased in a graded fashion with age. Hypertension was positively associated with DM in all groups and retention to care was negatively associated with the outcome in groups 1 and 3. CONCLUSION: This large-scale population-based study has revealed a relatively lower incidence of DM among PWH than some other US States. The evolving risk factors over time underline the need for maintaining retention to care to prevent the occurrence of DM.

Low-intensity pulsed ultrasound (LIPUS) promotes skeletal muscle regeneration by regulating PGC-1α/AMPK/GLUT4 pathways in satellite cells/myoblasts.

Low-Intensity Pulsed Ultrasound (LIPUS) holds therapeutic potential in promoting skeletal muscle regeneration, a biological process mediated by satellite cells and myoblasts. Despite their central roles in regeneration, the detailed mechanistic of LIPUS influence on satellite cells and myoblasts are not fully underexplored. In the current investigation, we administrated LIPUS treatment to injured skeletal muscles and C2C12 myoblasts over five consecutive days. Muscle samples were collected on days 6 and 30 post-injury for an in-depth histological and molecular assessment, both in vivo and in vitro with immunofluorescence analysis. During the acute injury phase, LIPUS treatment significantly augmented the satellite cell population, concurrently enhancing the number and size of newly formed myofibers whilst reducing fibrosis levels. At 30 days post-injury, the LIPUS-treated group demonstrated a more robust satellite cell pool and a higher myofiber count, suggesting that early LIPUS intervention facilitates satellite cell proliferation and differentiation, thereby promoting long-term recovery. Additionally, LIPUS markedly accelerated C2C12 myoblast differentiation, with observed increases in AMPK phosphorylation in myoblasts, leading to elevated expression of Glut4 and PGC-1α, and subsequent glucose uptake and mitochondrial biogenesis. These findings imply that LIPUS-induced modulation of myoblasts may culminate in enhanced cellular energy availability, laying a theoretical groundwork for employing LIPUS in ameliorating skeletal muscle regeneration post-injury. NEW & NOTEWORTHY: Utilizing the cardiotoxin (CTX) muscle injury model, we investigated the influence of LIPUS on satellite cell homeostasis and skeletal muscle regeneration. Our findings indicate that LIPUS promotes satellite cell proliferation and differentiation, thereby facilitating skeletal muscle repair. Additionally, in vitro investigations lend credence to the hypothesis that the regulatory effect of LIPUS on satellite cells may be attributed to its capability to enhance cellular energy metabolism.

L-arginine metabolism ameliorates age-related cognitive impairment by Amuc_1100-mediated gut homeostasis maintaining.

Aging-induced cognitive impairment is associated with a loss of metabolic homeostasis and plasticity. An emerging idea is that targeting key metabolites is sufficient to impact the function of other organisms. Therefore, more metabolism-targeted therapeutic intervention is needed to improve cognitive impairment. We first conducted untargeted metabolomic analyses and 16S rRNA to identify the aging-associated metabolic adaption and intestinal microbiome change. Untargeted metabolomic analyses of plasma revealed L-arginine metabolic homeostasis was altered during the aging process. Impaired L-arginine metabolic homeostasis was associated with low abundance of intestinal Akkermansia muciniphila (AKK) colonization in mice. Long-term supplementation of AKK outer membranes protein-Amuc_1100, rescued the L-arginine level and restored cognitive impairment in aging mice. Mechanically, Amuc_1100 acted directly as a source of L-arginine and enriched the L-arginine-producing bacteria. In aged brain, Amuc_1100 promoted the superoxide dismutase to alleviated oxidation stress, and increased nitric oxide, derivatives of L-arginine, to improve synaptic plasticity. Meanwhile, L-arginine repaired lipopolysaccharide-induced intestinal barrier damage and promoted growth of colon organoid. Our findings indicated that aging-related cognitive impairment was closely associated with the disorders of L-arginine metabolism. AKK-derived Amuc_1100, as a potential postbiotic, targeting the L-arginine metabolism, might provide a promising therapeutic strategy to maintain the intestinal homeostasis and cognitive function in aging.

Suicide Ideation and Attempt Among People With HIV: A Statewide Population-level Cohort Analysis Between 2005 and 2020.

BACKGROUND: Risk factors for suicidality among people with HIV (PWH) may evolve over their disease course, particularly as they develop comorbidities such as mental health disorders over time. SETTING: This study compared the leading risk factors of suicide ideation/attempt among PWH in South Carolina across different combination antiretroviral therapy (cART) eras. METHODS: A statewide cohort of PWH who were diagnosed between 2005 and 2016, with a follow-up record until 2020, was involved in the study. A Cox proportional hazards model was used to examine the association of suicide ideation/attempt and predictors, including demographics, HIV-related characteristics, and mental health conditions. RESULTS: Among 8567 PWH, the incidence of suicide ideation/attempt increased from 537.7 per 100,000 person-years [95% confidence interval (CI): 460.2 to 615.1] in the early cART cohort (2005-2008) to 782.5 (95% CI: 697.6 to 867.4) in the late cART cohort (2009-2016). Leading risk factors of suicide ideation/attempt changed across the cART cohort. In the early cART cohort, PWH with suicide ideation/attempt were more likely to be White and diagnosed with bipolar disorder ( P' s < 0.05). In the late cART cohort, suicide ideation/attempt was positively associated with transmission through injection drug use, anxiety, posttraumatic stress disorder, schizophrenia, and personality disorder ( P' s < 0.05). CONCLUSIONS: Mental health conditions have emerged as more prominent risk factors for suicide ideation/attempt in the late cART cohort. Enhanced access to psychiatric care could facilitate the early identification of mental health conditions, enabling timely counseling or psychosocial interventions that may mitigate mental health issues and, consequently, reduce the likelihood of suicide ideation/attempts among PWH.

COVID-19 breakthrough infections among people living with and without HIV: A statewide cohort analysis.

OBJECTIVES: This study aims to characterize and compare COVID-19 breakthrough infections between people living with and without HIV across different phases of the pandemic. METHODS: Using statewide HIV cohort data, the study population included adult residents in South Carolina (SC) (>18 years old) who were fully vaccinated between January 02, 2021 and April 14, 2022 when Alpha, Delta, and Omicron variants were circulating in SC. We used the Cox proportional hazard model to investigate the association between HIV infection and breakthrough infection, adjusting for relevant covariates. RESULTS: Among 2,144,415 vaccinated individuals, 8,335 were people living with HIV (PLWH) and 2,136,080 were people without HIV (PWoH). After propensity score matching, HIV infection was not significantly associated with breakthrough infection rate. However, when comparing breakthrough infections among individuals without any booster dose, PLWH had a higher risk of breakthrough infections (adjusted Hazard Ration: 1.19; 95% confidence interval: 1.03-1.39). Compared to PWoH, PLWH with high levels of clusters of differentiation 4 (CD4) count or viral suppression were not associated with breakthrough infections. CONCLUSIONS: Our findings do not support a broad conclusion that COVID-19 vaccine effectiveness is lower among PLWH, while we did find that PLWH had a higher risk of breakthrough infection compared to PWoH if they did not receive a booster dose.

Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy: A Multicenter Prospective Randomized Controlled Study.

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging.

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions, such as developing and preserving the skeletal muscle system. However, the interplay between gut microbiota/metabolites and the regulation of satellite cell (SC) homeostasis, particularly during aging, remains elusive. We propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development, regeneration, and aging process. Our investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice, leads to the activation of SCs or a significant reduction in the total number. Furthermore, employing multi-omics (e.g., RNA-seq, 16S rRNA gene sequencing, and metabolomics) and bioinformatic analysis, we demonstrate that the reduced butyrate levels, alongside the gut microbial dysbiosis, could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle aging. Meanwhile, butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota, potentially by inhibiting the proliferation and differentiation of SCs/myoblasts. The butyrate effect is likely facilitated through the monocarboxylate transporter 1 (Mct1), a lactate transporter enriched on membranes of SCs and myoblasts. As a result, butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle aging. Our findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

Ecologic analysis of antimicrobial use in South Carolina hospitals during 2020-2022.

Background: Factors influencing excessive antimicrobial utilization in hospitalized patients remain poorly understood, particularly with the COVID-19 pandemic. Methods: In this retrospective cohort, we compared administrative data regarding antimicrobial prescriptions in hospitalized patients in South Carolina from March 2020 through September 2022. The study examined variables associated with antimicrobial use across demographics, COVID status, and length of stay, among other variables. Results: Significant relationships were seen with antimicrobial use in COVID-19 positive patients (OR 2.00, 95% Confidence Interval (CI): 1.9-2.1), young adults (OR 1.08, 95% CI: 0.99-1.12, COVID-19 positive Blacks and Hispanics (OR 1.06, 95% CI: 1.01-1.11, OR 1.05, 95% CI: 0.89-1.23), and COVID-19 positive patients with ≥2 comorbid conditions (OR 1.55, 95% CI: 1.43-1.68). Discussion: Further analysis in more than one healthcare system should explore these ecologic relationships further to understand if these are common trends to inform ongoing stewardship interventions.

COVID-19 Testing Among People with HIV: A Population Level Analysis Based on Statewide Data in South Carolina.

People with HIV (PWH) are at an elevated risk of developing severe COVID-19 outcomes because of compromised immunity and more comorbidities. However, existing literature suggests a lower rate of COVID-testing among PWH. This study aimed to explore the temporal trend of county-level COVID-19 testing rate and multi-level predictors of COVID-19 ever-testing among PWH in South Carolina (SC). Leveraging linked statewide HIV and COVID-19 datasets, we defined the study population as all adult (18 + years) PWH who were alive on March 2020 and living in SC. PWH with a COVID-19 testing record between March 2020 and October 2021 were defined as COVID-19 ever-testers. Logistic regression and generalized mixed models were used to investigate the association of PWH's demographic profile, HIV clinical characteristics (e.g., CD4 count, viral load), comorbidities, and social factors with COVID-19 testing among PWH. Among 15,660 adult PWH, 8,005 (51.12%) had ever tested for COVID-19 during the study period (March 2020-October 2021). PWH with older age, being male, and Hispanics were less likely to take COVID-19 testing, while men who have sex with men or injection drug users were more likely to take COVID-19 testing. PWH with higher recent viral load (10,000-100,000 copies/ml vs. <200 copies/ml: adjusted odds ratio [AOR]: 0.64, 95%CI: 0.55-0.75) and lower CD4 counts (> 350 cells/mm3 vs. <200 cells/mm3: AOR: 1.25, 95%CI: 1.09-1.45) had lower odds for COVID-19 testing. Additionally, PWH with lower comorbidity burden and those living in rural areas were less likely to be tested for COVID-19. Differences in COVID-19 test-seeking behaviors were observed among PWH in the current study, which could help provide empirical evidence to inform the prioritization of further disease monitoring and targeted intervention. More efforts on building effective surveillance and screening systems are needed to allow early case detection and curbing disease transmission among older, male, Hispanic, and immune-suppressed PWH, especially in rural areas.

Lactobacillus Intestinalis Primes Epithelial Cells to Suppress Colitis-Related Th17 Response by Host-Microbe Retinoic Acid Biosynthesis.

Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate-induced colitis in mice. Based on flow cytometry, colitis-associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell-null Rag1-/- mice or upon anti-IL-17-A antibody-treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA-driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti-colitis effect in RAR-α -mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA-SAA1/2-Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity.

Heat-inactivated Bifidobacterium adolescentis ameliorates colon senescence through Paneth-like-cell-mediated stem cell activation.

Declined numbers and weakened functions of intestinal stem cells (ISCs) impair the integrity of the intestinal epithelium during aging. However, the impact of intestinal microbiota on ISCs in this process is unclear. Here, using premature aging mice (telomerase RNA component knockout, Terc-/-), natural aging mice, and in vitro colonoid models, we explore how heat-inactivated Bifidobacterium adolescentis (B. adolescentis) affects colon senescence. We find that B. adolescentis could mitigate colonic senescence-related changes by enhancing intestinal integrity and stimulating the regeneration of Lgr5+ ISCs via Wnt/ß-catenin signaling. Furthermore, we uncover the involvement of Paneth-like cells (PLCs) within the colonic stem-cell-supporting niche in the B. adolescentis-induced ISC regeneration. In addition, we identify soluble polysaccharides (SPS) as potential effective components of B. adolescentis. Overall, our findings reveal the role of heat-inactivated B. adolescentis in maintaining the ISCs regeneration and intestinal barrier, and propose a microbiota target for ameliorating colon senescence.

Disease severity of COVID-19 in different phases of the pandemic: Do healthcare workers have better outcomes?

Background: This study aimed to characterize and compare the demographics, clinical profile, and COVID-19 outcomes between healthcare workers (HCWs) and non-HCWs COVID-19 patients diagnosed in different phases of the pandemic defined by the vaccine rollout policy and different variants that circulated in South Carolina (SC). Methods: Extracted from the statewide electronic health record data, we analyzed the clinical outcome of 34,502 HCWs and 1,071,020 non-HCWs adults diagnosed with SARS-CoV-2 between March 2, 2020 to April 14, 2022. Logistic regression models were used to explore the association between different pandemic phases and COVID-19 severity-related outcomes. Results: Substantial reductions in mortality were observed following the vaccine rollout in non-HCWs and HCWs. Compared to the pre-vaccination period, non-HCWs patients diagnosed during post-vaccination with Alpha predominance (adjusted odds ratio [aOR]: 1.10; 95%CI: 1.04-1.16) were more likely to be hospitalized, but the reduced mortality rates were observed in all post-vaccination periods. Regarding HCWs, a reduced mortality rate was only observed in the pre-Alpha (aOR: 0.33; 95%CI: 0.13-0.84) and Omicron periods (aOR: 0.21; 95%CI: 0.05-0.89). Conclusions: The declining protection effect of vaccines informs the importance of early promotion of the booster dose of the COVID-19 vaccine for HCWs who have more occupational exposure.

Gut microbiota in muscular atrophy development, progression, and treatment: New therapeutic targets and opportunities.

Skeletal muscle atrophy is a debilitating condition that significantly affects quality of life and often lacks effective treatment options. Muscle atrophy can have various causes, including myogenic, neurogenic, and other factors. Recent investigation has underscored a compelling link between the gut microbiota and skeletal muscle. Discerning the potential differences in the gut microbiota associated with muscle atrophy-related diseases, understanding their influence on disease development, and recognizing their potential as intervention targets are of paramount importance. This review aims to provide a comprehensive overview of the role of the gut microbiota in muscle atrophy-related diseases. We summarize clinical and pre-clinical studies that investigate the potential for gut microbiota modulation to enhance muscle performance and promote disease recovery. Furthermore, we delve into the intricate interplay between the gut microbiota and muscle atrophy-related diseases, drawing from an array of studies. Emerging evidence suggests significant differences in gut microbiota composition in individuals with muscle atrophy-related diseases compared with healthy individuals. It is conceivable that these alterations in the microbiota contribute to the pathogenesis of these disorders through bacterium-related metabolites or inflammatory signals. Additionally, interventions targeting the gut microbiota have demonstrated promising results for mitigating disease progression in animal models, underscoring the therapeutic potential of modulating the gut microbiota in these conditions. By analyzing the available literature, this review sheds light on the involvement of the gut microbiota in muscle atrophy-related diseases. The findings contribute to our understanding of the underlying mechanisms and open avenues for development of novel therapeutic strategies targeting the gut-muscle axis.

Base-Controlled Divergent Synthesis of Fluorine-Containing Benzo[4,5]imidazo[2,1-b][1,3]thiazines from 2-Mercaptobenzimidazoles and ß-CF3-1,3-Enynes.

A base-controlled divergent cyclization between 2-mercaptobenzimidazoles and ß-CF3-1,3-enynes providing either trifluoromethylated or fluorinated benzo[4,5]imidazo[2,1-b][1,3]thiazines has been developed. The ß-CF3-1,3-enyne, as a three-carbon synthon, underwent a 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU)-catalyzed tandem hydroamination/intramolecular hydrothiolation to give CF3-substituted 3,4-dihydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thiazine, whereas reaction with KOH afforded fluorinated 4H-benzo[4,5]imidazo[2,1-b][1,3]thiazine exclusively. In addition, the synthetic utility of this methodology was showcased through a variety of downstream derivatizations.

Bifidobacterium adolescentis orchestrates CD143+ cancer-associated fibroblasts to suppress colorectal tumorigenesis by Wnt signaling-regulated GAS1.

BACKGROUND: The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is not well explored. Here, we elucidated the functional role of Bifidobacterium adolescentis (B.a) on CRC and investigated its possible mechanism on the manipulation of cancer-associated fibroblasts (CAFs) in CRC. METHODS: Different CRC animal models and various cell line models were established to explore the function of B.a on CRC. The single-cell RNA sequencing (scRNA-seq) or flow cytometry was used to detect the cell subsets in the TME of CRC. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), or immunofluorescence staining were performed to examine the activation of Wnt signaling and growth arrest specific 1 (GAS1) on CD143+ CAFs. Chromatin immunoprecipitation quantitative real-time PCR (CHIP-qPCR) was performed to investigate the regulation of transcription factor 4 (TCF4) on GAS1. Multi-immunofluorescence assay examined the expression level of CD143 and GAS1 on tissue microarray. RESULTS: We found that B.a abundance was significantly reduced in CRC patients from two independent cohorts and the bacteria database of GMrepo. Supplementation with B.a suppressed ApcMin/+ spontaneous or AOM/DSS-induced tumorigenesis in mice. scRNA-seq revealed that B.a facilitated a subset of CD143+ CAFs by inhibiting the infiltration of Th2 cells, while promoting the TNF-alpha+ B cells in TME. CD143+ CAFs highly expressed GAS1 and exhibited tumor suppressive effect. Mechanistically, GAS1 was activated by the Wnt/ß-catenin signaling in CD143+ CAFs. B.a abundance was correlated with the expression level of CD143 and GAS1. The level of CD143+ CAFs predicted the better survival outcome in CRC patients. CONCLUSIONS: These results highlighted that B.a induced a new subset of CD143+ CAFs by Wnt signaling-regulated GAS1 to suppress tumorigenesis and provided a novel therapeutic target for probiotic-based modulation of TME in CRC.