Lactobacillus lactis and Pediococcus pentosaceus-driven reprogramming of gut microbiome and metabolome ameliorates the progression of non-alcoholic fatty liver disease.

BACKGROUND: Although microbioa-based therapies have shown putative effects on the treatment of non-alcoholic fatty liver disease (NAFLD), it is not clear how microbiota-derived metabolites contribute to the prevention of NAFLD. We explored the metabolomic signature of Lactobacillus lactis and Pediococcus pentosaceus in NAFLD mice and its association in NAFLD patients. METHODS: We used Western diet-induced NAFLD mice, and L. lactis and P. pentosaceus were administered to animals in the drinking water at a concentration of 109 CFU/g for 8 weeks. NAFLD severity was determined based on liver/body weight, pathology and biochemistry markers. Caecal samples were collected for the metagenomics by 16S rRNA sequencing. Metabolite profiles were obtained from caecum, liver and serum. Human stool samples (healthy control [n = 22] and NAFLD patients [n = 23]) were collected to investigate clinical reproducibility for microbiota-derived metabolites signature and metabolomics biomarker. RESULTS: L. lactis and P. pentosaceus supplementation effectively normalized weight ratio, NAFLD activity score, biochemical markers, cytokines and gut-tight junction. While faecal microbiota varied according to the different treatments, key metabolic features including short chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites were analogously restored by both probiotic supplementations. The protective effects of indole compounds were validated with in vitro and in vivo models, including anti-inflammatory effects. The metabolomic signatures were replicated in NAFLD patients, accompanied by the comparable levels of Firmicutes/Bacteroidetes ratio, which was significantly higher (4.3) compared with control (0.6). Besides, the consequent biomarker panel with six stool metabolites (indole, BAs, and SCFAs) showed 0.922 (area under the curve) in the diagnosis of NAFLD. CONCLUSIONS: NAFLD progression was robustly associated with metabolic dys-regulations in the SCFAs, bile acid and indole compounds, and NAFLD can be accurately diagnosed using the metabolites. L. lactis and P. pentosaceus ameliorate NAFLD progression by modulating gut metagenomic and metabolic environment, particularly tryptophan pathway, of the gut-liver axis.

Lactobacillus spp. create a protective micro-ecological environment through regulating the core fucosylation of vaginal epithelial cells against cervical cancer.

Vaginal dysbiosis often occurs in patients with cervical cancer. The fucosylation of mucosal epithelial cells is closely related to microbial colonization, and play an important role in protecting the vaginal mucosal epithelial cells. However, no reports on the relationship between vaginal dysbiosis and abnormal mucosal epithelial cell fucosylation, and their roles in the occurrence and development of cervical cancer are unavailable. Here we report that core fucosylation levels were significantly lower in the serum, exfoliated cervical cells and tumor tissue of cervical cancer patients. Core fucosyltransferase gene (Fut8) knockout promoted the proliferation and migration of cervical cancer cells. In patients with cervical cancer, the vaginal dysbiosis, and the abundance of Lactobacillus, especially L. iners, was significantly reduced. Meanwhile, the abundance of L.iners was positively correlated with core fucosylation levels. The L. iners metabolite lactate can activate the Wnt pathway through the lactate-Gpr81 complex, which increases the level of core fucosylation in epidermal cells, inhibiting the proliferation and migration of cervical cancer cells, and have application prospects in regulating the vaginal microecology and preventing cervical cancer.

Age and the aging process significantly alter the small bowel microbiome.

Gut microbial diversity decreases with aging, but existing studies have used stool samples, which do not represent the entire gut. We analyzed the duodenal microbiome in 251 subjects aged 18-35 (n = 32), 36-50 (n = 41), 51-65 (n = 96), and 66-80 (n = 82). Decreased duodenal microbial diversity in older subjects is associated with combinations of chronological age, number of concomitant diseases, and number of medications used, and also correlated with increasing coliform numbers (p < 0.0001). Relative abundance (RA) of phylum Proteobacteria increases in older subjects, with increased RA of family Enterobacteriaceae and coliform genera Escherichia and Klebsiella, and is associated with alterations in the RA of other duodenal microbial taxa and decreased microbial diversity. Increased RA of specific genera are associated with chronological age only (Escherichia, Lactobacillus, and Enterococcus), number of medications only (Klebsiella), or number of concomitant diseases only (Clostridium and Bilophila). These findings indicate the small intestinal microbiome changes significantly with age and the aging process.

Intricate Connections between the Microbiota and Endometriosis.

Imbalances in gut and reproductive tract microbiota composition, known as dysbiosis, disrupt normal immune function, leading to the elevation of proinflammatory cytokines, compromised immunosurveillance and altered immune cell profiles, all of which may contribute to the pathogenesis of endometriosis. Over time, this immune dysregulation can progress into a chronic state of inflammation, creating an environment conducive to increased adhesion and angiogenesis, which may drive the vicious cycle of endometriosis onset and progression. Recent studies have demonstrated both the ability of endometriosis to induce microbiota changes, and the ability of antibiotics to treat endometriosis. Endometriotic microbiotas have been consistently associated with diminished Lactobacillus dominance, as well as the elevated abundance of bacterial vaginosis-related bacteria and other opportunistic pathogens. Possible explanations for the implications of dysbiosis in endometriosis include the Bacterial Contamination Theory and immune activation, cytokine-impaired gut function, altered estrogen metabolism and signaling, and aberrant progenitor and stem-cell homeostasis. Although preliminary, antibiotic and probiotic treatments have demonstrated efficacy in treating endometriosis, and female reproductive tract (FRT) microbiota sampling has successfully predicted disease risk and stage. Future research should aim to characterize the "core" upper FRT microbiota and elucidate mechanisms behind the relationship between the microbiota and endometriosis.

Meta-analysis identifies the effect of dietary multi-enzyme supplementation on gut health of pigs.

Gut health though is not well defined the role of gastrointestinal tract is vital if an animal must perform well. Apart from digestion, secretion, and absorption gut is harbored with consortium of microbiota which plays a key role in one's health. Enzymes, one of the alternatives for antibiotics with beneficial effects on digestion and consistency of food and its effect on gut health. The effect of enzyme supplementation on gut health is not well established and the objective of this meta-analysis is to investigate if the enzyme supplement has influence on gut. This meta-analysis includes 1221 experiments which has single enzyme studies and or studies with multiple enzyme complexes but not challenged. The ratio of Lactobacillus and E. coli is related to ADFI which showed comparatively lower negative correlation coefficient, with - 0.052 and - 0.035, respectively, whose I2 values are below 25%, showing that these studies show a significantly lower level of heterogeneity. Correlation between villus height, crypt depth, their ratio and fatty acid is also assessed, and it showed that when the animal is supplemented with two enzyme complexes resulted in positive gut health rather than the single or more than two enzymes.

Genotoxicity and subchronic general toxicity assessments of Lactobacillus curvatus WiKim 38 using Sprague-Dawley rats.

Lactobacillus curvatus WiKim 38 (LCW), isolated from kimchi, has shown novel immunomodulatory and anti-inflammatory properties. In the present study, to obtain data on the safety of LCW, we performed three genotoxicity (bacterial reverse mutation, chromosome aberration, and micronucleus) and two general toxicity (single-dosing and 13-week repeated-dosing) studies. In the genotoxicity assessment, LCW showed no increased reverse mutation for 4 strains of Salmonella typhimurium and a strain of Escherichia coli. In addition, LCW did not induce chromosome aberrations at concentrations up to 5000 µg/mL in cultured Chinese hamster lung (CHL) cells and did not induce an increased frequency of micronuclei in the bone marrow cells of rats at concentrations up to 2000 mg/kg. In the acute toxicity study using Sprague-Dawley (SD) rats, the approximate lethal dose of LCW was determined to be over 5000 mg/kg body weight (b.w.) in both sexes. Finally, in the subchronic toxicity study, no LCW-related adverse effects were observed at concentrations up to 5000 mg/kg b.w./day. Consequently, LCW is considered not to have mutagenic effects, and its no-observed-adverse-effect-level (NOAEL) is 5000 mg/kg b.w., equivalent to approximately 4.71 × 109 CFU/kg b.w., suggesting the LCW could be a potential probiotic for humans based on its safety profile.

Mediation of the microbiome-gut axis by oyster (Crassostrea gigas) polysaccharides: A possible protective role in alcoholic liver injury.

The objective of this study was to evaluate the molecular mechanism by which polysaccharides from Crassostrea gigas (RPS) prevent alcoholic liver injury and to uncover whether the steaming process affects the bioactivities of RPS. Oral administration of RPS or polysaccharides from steamed oyster (SPS) (282 mg/kg b.w.) significantly attenuated alcoholic liver injury in mice. RPS and SPS treatments protected gut functions by significantly enhancing the expression of tight-junction proteins and suppressing inflammatory responses. RPS and SPS treatments also significantly increased Lactobacillus reuteri and Roseburia spp. and decreased the level of Escherichia. Microbial metabolites, especially propionate and butyrate, were also increased in RPS- and SPS-treated mice. Correlation analysis revealed that the beneficial effects of RPS and SPS were strongly correlated with the microbiota composition and SCFAs. These results indicated that oyster polysaccharides alleviated alcoholic liver injury by mediating the gut-liver-metabolite axis, and the steaming process had little influence on the bioactivity.

Oral probiotic activities and biosafety of Lactobacillus gasseri HHuMIN D.

BACKGROUND: Lactobacillus spp. have been researched worldwide and are used in probiotics, but due to difficulties with laboratory cultivation of and experimentation on oral microorganisms, there are few reports of Lactobacillus spp. being isolated from the oral cavity and tested against oral pathogens. This research sought to isolate and determine the safety and inhibitory capabilities of a Lactobacillus culture taken from the human body. RESULTS: One organism was isolated, named "L. gasseri HHuMIN D", and evaluated for safety. A 5% dilution of L. gasseri HHuMIN D culture supernatant exhibited 88.8% inhibition against halitosis-producing anaerobic microorganisms and the organism itself exhibited powerful inhibitory effects on the growth of 11 oral bacteria. Hydrogen peroxide production reached 802 µmol/L after 12 h and gradually diminished until 24 h, it efficiently aggregated with P. catoniae and S. sanguinis, and it completely suppressed S. mutans-manufactured artificial dental plaque. L. gasseri HHuMIN D's KB cell adhesion capacity was 4.41 cells per cell, and the cell adhesion of F. nucleatum and S. mutans diminished strongly in protection and displacement assays. CONCLUSION: These results suggest that L. gasseri HHuMIN D is a safe, bioactive, lactobacterial food ingredient, starter culture, and/or probiotic microorganism for human oral health.

Lactobacillus strains vary in their ability to interact with human endometrial stromal cells.

The placental membranes that surround the fetus during pregnancy were suggested to contain a low abundance microbiota. Specifically, abundance of Lactobacillus, a probiotic and dominant member of the microbiome of the lower reproductive tract, has been shown to correlate with healthy, term pregnancies. We therefore sought to assess the interactions between four different Lactobacillus strains with immortalized decidualized endometrial cells (dT-HESCs), which were used as a model to represent the outermost layer of the placental membranes. Notably, we demonstrated that all four Lactobacillus strains could associate with dT-HESCs in vitro. L. crispatus was significantly more successful (p < 0.00005), with 10.6% of bacteria attaching to the host cells compared to an average of 0.8% for the remaining three strains. The four strains also varied in their ability to form biofilms. Dependent on media type, L. reuteri 6475 formed the strongest biofilms in vitro. To examine the impact on immune responses, levels of total and phosphorylated protein p38, a member of the Mitogen Activated Protein Kinase (MAPK) pathway, were examined following Lactobacillus association with dT-HESCs. Total levels of p38 were reduced to an average of 44% that of the cells without Lactobacillus (p < 0.05). While a trend towards a reduction in phosphorylated p38 was observed, this difference was not significant (p > 0.05). In addition, association with Lactobacillus did not result in increased host cell death. Collectively, these data suggest that varying types of Lactobacillus can attach to the outermost cells of the placental membranes and that these interactions do not contribute to inflammatory responses or host cell death. To our knowledge this is the first in vitro study to support the ability of Lactobacillus to interact with placental cells, which is important when considering its use as a potential probiotic within the reproductive tract.

Probiotic Lactobacillus and Bifidobacterium Strains Counteract Adherent-Invasive Escherichia coli (AIEC) Virulence and Hamper IL-23/Th17 Axis in Ulcerative Colitis, but Not in Crohn's Disease.

Hypersecretion of proinflammatory cytokines and dysregulated activation of the IL-23/Th17 axis in response to intestinal microbiota dysbiosis are key factors in the pathogenesis of inflammatory bowel diseases (IBD). In this work, we studied how Lactobacillus and Bifidobacterium strains affect AIEC-LF82 virulence mechanisms and the consequent inflammatory response linked to the CCR6-CCL20 and IL-23/Th17 axes in Crohn's disease (CD) and ulcerative colitis (UC) patients. All Lactobacillus and Bifidobacterium strains significantly reduced the LF82 adhesion and persistence within HT29 intestinal epithelial cells, inhibiting IL-8 secretion while not affecting the CCR6-CCL20 axis. Moreover, they significantly reduced LF82 survival within macrophages and dendritic cells, reducing the secretion of polarizing cytokines related to the IL-23/Th17 axis, both in healthy donors (HD) and UC patients. In CD patients, however, only B. breve Bbr8 strain was able to slightly reduce the LF82 persistence within dendritic cells, thus hampering the IL-23/Th17 axis. In addition, probiotic strains were able to modulate the AIEC-induced inflammation in HD, reducing TNF-α and increasing IL-10 secretion by macrophages, but failed to do so in IBD patients. Interestingly, the probiotic strains studied in this work were all able to interfere with the IL-23/Th17 axis in UC patients, but not in CD patients. The different interaction mechanisms of probiotic strains with innate immune cells from UC and CD patients compared to HD suggest that testing on CD-derived immune cells may be pivotal for the identification of novel probiotic strains that could be effective also for CD patients.

Comparison of microbiota in the cloaca, colon, and magnum of layer chicken.

Anatomically terminal parts of the urinary, reproductive, and digestive systems of birds all connect to the cloaca. As the feces drain through the cloaca in chickens, the cloacal bacteria were previously believed to represent those of the digestive system. To investigate similarities between the cloacal microbiota and the microbiota of the digestive and reproductive systems, microbiota inhabiting the colon, cloaca, and magnum, which is a portion of the chicken oviduct of 34-week-old, specific-pathogen-free hens were analyzed using a 16S rRNA metagenomic approach using the Ion torrent sequencer and the Qiime2 bioinformatics platform. Beta diversity via unweighted and weighted unifrac analyses revealed that the cloacal microbiota was significantly different from those in the colon and the magnum. Unweighted unifrac revealed that the cloacal microbiota was distal from the microbiota in the colon than from the microbiota in the magnum, whereas weighted unifrac revealed that the cloacal microbiota was located further away from the microbiota in the magnum than from the microbiota inhabiting the colon. Pseudomonas spp. were the most abundant in the cloaca, whereas Lactobacillus spp. and Flavobacterium spp. were the most abundant species in the colon and the magnum. The present results indicate that the cloaca contains a mixed population of bacteria, derived from the reproductive, urinary, and digestive systems, particularly in egg-laying hens. Therefore, sampling cloaca to study bacterial populations that inhabit the digestive system of chickens requires caution especially when applied to egg-laying hens. To further understand the physiological role of the microbiota in chicken cloaca, exploratory studies of the chicken's cloacal microbiota should be performed using chickens of different ages and types.

Lactobacillus Strains Alleviated Hyperlipidemia and Liver Steatosis in Aging Rats via Activation of AMPK.

In this study, we hypothesized that different strains of Lactobacillus can alleviate hyperlipidemia and liver steatosis via activation of 5' adenosine monophosphate-activated protein kinase (AMPK), an enzyme that is involved in cellular energy homeostasis, in aged rats. Male rats were fed with a high-fat diet (HFD) and injected with D-galactose daily over 12 weeks to induce aging. Treatments included (n = 6) (i) normal diet (ND), (ii) HFD, (iii) HFD-statin (lovastatin 2 mg/kg/day), (iv) HFD-Lactobacillus fermentum DR9 (10 log CFU/day), (v) HFD-Lactobacillus plantarum DR7 (10 log CFU/day), and (vi) HFD-Lactobacillus reuteri 8513d (10 log CFU/day). Rats administered with statin, DR9, and 8513d reduced serum total cholesterol levels after eight weeks (p < 0.05), while the administration of DR7 reduced serum triglycerides level after 12 weeks (p < 0.05) as compared to the HFD control. A more prominent effect was observed from the administration of DR7, where positive effects were observed, ranging from hepatic gene expressions to liver histology as compared to the control (p < 0.05); downregulation of hepatic lipid synthesis and ß-oxidation gene stearoyl-CoA desaturase 1 (SCD1), upregulation of hepatic sterol excretion genes of ATP-binding cassette subfamily G member 5 and 8 (ABCG5 and ABCG8), lesser degree of liver steatosis, and upregulation of hepatic energy metabolisms genes AMPKα1 and AMPKα2. Taken altogether, this study illustrated that the administration of selected Lactobacillus strains led to improved lipid profiles via activation of energy and lipid metabolisms, suggesting the potentials of Lactobacillus as a promising natural intervention for alleviation of cardiovascular and liver diseases.

In vitro characteristics of intravaginal Lactobacilli; why is L. iners detected in abnormal vaginal microbial flora?

PURPOSE: Our purpose is to investigate the reasons why Lactobacillus iners is detected in abnormal vaginal microbial flora. METHODS: In this study, in vitro characteristics of four type strains (L. crispatus, L. iners, L. gasseri, and L. jensenii) were examined by measuring the growth speed by OD660, and acid resistance, with gram stain and Live/Dead stain. RESULTS: The growth speed was L. gasseri > L. jensenii > L. crispatus > L. iners. Bacterial counts of all Lactobacilli in MRS medium began to decrease at the middle of the log-phase of the growth curve. In addition, L. iners grew to 106 CFU/mL and the others grew to 108 CFU/mL. L. iners was mostly Gram-negative with very short rod, while the others were mostly Gram-positive rods. L. iners was completely killed in the pH 3 medium, however, the others grew (in pH 3 medium) in 1/100 order compared with those in the pH 6 medium. CONCLUSION: L. iners was not a typical gram-positive long rod Lactobacilli and presented weak acid-resistance. The reasons why L. iners is detected in abnormal vaginal microbial flora were presumed to be due to the unique morphologic and microbiologic characteristics.

Lactobacilli Have a Niche in the Human Nose.

Although an increasing number of beneficial microbiome members are characterized for the human gut and vagina, beneficial microbes are underexplored for the human upper respiratory tract (URT). In this study, we demonstrate that taxa from the beneficial Lactobacillus genus complex are more prevalent in the healthy URT than in patients with chronic rhinosinusitis (CRS). Several URT-specific isolates are cultured, characterized, and further explored for their genetic and functional properties related to adaptation to the URT. Catalase genes are found in the identified lactobacilli, which is a unique feature within this mostly facultative anaerobic genus. Moreover, one of our isolated strains, Lactobacillus casei AMBR2, contains fimbriae that enable strong adherence to URT epithelium, inhibit the growth and virulence of several URT pathogens, and successfully colonize nasal epithelium of healthy volunteers. This study thus demonstrates that specific lactobacilli are adapted to the URT and could have a beneficial keystone function in this habitat.

Friend or foe? Lactobacillus in the context of autoimmune disease.

Over the last decade, the interplay between the gut microbiota, the consortium of intestinal microbes that colonizes intestinal mucosal barriers, and its host immune system has been increasingly better understood. Disruption of the delicate balance between beneficial and pathogenic commensals, known as dysbiosis, contributes to a variety of chronic immunologic and metabolic diseases. Complicating this paradigm are bacterial strains that can operate paradoxically both as instigators and attenuators of inflammatory responses, depending on host background. Here, we review the role of several strains in the genus Lactobacillus within the context of autoimmune and other chronic disorders with a predominant focus on L. reuteri. While strains within this species have been shown to provide immune health benefits, they have also been demonstrated to act as a pathobiont in autoimmune-prone hosts. Beneficial functions in healthy hosts include competing with pathogenic microbes, promoting regulatory T cell development, and protecting the integrity of the gut barrier. On the other hand, certain strains can also break through a dysfunctional gut barrier, colonize internal tissues such as the spleen or liver and promote inflammatory responses in host tissues that lead to autoimmune disease. This review summarizes the manifold roles that these commensals play in the context of health and disease.

In vitro assessment of immunomodulatory and anti-Campylobacter activities of probiotic lactobacilli.

The present study was undertaken to assess the antimicrobial activity of Lactobacillus spp. (L. salivarius, L. johnsonii, L. reuteri, L. crispatus, and L. gasseri) against Campylobacter jejuni as well as their immunomodulatory capabilities. The results demonstrated that lactobacilli exhibit differential antagonistic effects against C. jejuni and vary in their ability to elicit innate responses in chicken macrophages. All lactobacilli exerted inhibitory effects on C. jejuni growth, abrogated the production of the quorum sensing molecule autoinducer-2 (AI-2) by C. jejuni and inhibited the invasion of C. jejuni in human intestinal epithelial cells. Additionally, all lactobacilli, except L. reuteri, significantly reduced the expression of virulence-related genes in C. jejuni, including genes responsible for motility (flaA, flaB, and flhA), invasion (ciaB), and AI-2 production (luxS). All lactobacilli enhanced C. jejuni phagocytosis by macrophages and increased the expression of interferon (IFN)-γ, interleukin (IL)-1ß, IL-12p40, IL-10, and chemokine (CXCLi2) in macrophages. Furthermore, L. salivarius, L. reuteri, L. crispatus, and a mixture of all lactobacilli significantly increased expression of the co-stimulatory molecules CD40, CD80, and CD86 in macrophages. In conclusion, these findings demonstrate that lactobacilli possess anti-Campylobacter and immunomodulatory activities. Further studies are needed to assess their protective efficacy against intestinal colonization by C. jejuni in broiler chickens.

Genomic and epidemiological evidence of bacterial transmission from probiotic capsule to blood in ICU patients.

Probiotics are routinely administered to hospitalized patients for many potential indications1 but have been associated with adverse effects that may outweigh their potential benefits2-7. It is particularly alarming that probiotic strains can cause bacteremia8,9, yet direct evidence for an ancestral link between blood isolates and administered probiotics is lacking. Here we report a markedly higher risk of Lactobacillus bacteremia for intensive care unit (ICU) patients treated with probiotics compared to those not treated, and provide genomics data that support the idea of direct clonal transmission of probiotics to the bloodstream. Whole-genome-based phylogeny showed that Lactobacilli isolated from treated patients' blood were phylogenetically inseparable from Lactobacilli isolated from the associated probiotic product. Indeed, the minute genetic diversity among the blood isolates mostly mirrored pre-existing genetic heterogeneity found in the probiotic product. Some blood isolates also contained de novo mutations, including a non-synonymous SNP conferring antibiotic resistance in one patient. Our findings support that probiotic strains can directly cause bacteremia and adaptively evolve within ICU patients.

Chitin-glucan and pomegranate polyphenols improve endothelial dysfunction.

The vascular dysfunction is the primary event in the occurrence of cardio-vascular risk, and no treatment exists until now. We tested for the first time the hypothesis that chitin-glucan (CG) - an insoluble fibre with prebiotic properties- and polyphenol-rich pomegranate peel extract (PPE) can improve endothelial and inflammatory disorders in a mouse model of cardiovascular disease (CVD), namely by modulating the gut microbiota. Male Apolipoprotein E knock-out (ApoE-/-) mice fed a high fat (HF) diet developed a significant endothelial dysfunction attested by atherosclerotic plaques and increasing abundance of caveolin-1 in aorta. The supplementation with CG + PPE in the HF diet reduced inflammatory markers both in the liver and in the visceral adipose tissue together with a reduction of hepatic triglycerides. In addition, it increased the activating form of endothelial NO-synthase in mesenteric arteries and the heme-nitrosylated haemoglobin (Hb-NO) blood levels as compared with HF fed ApoE-/- mice, suggesting a higher capacity of mesenteric arteries to produce nitric oxide (NO). This study allows to pinpoint gut bacteria, namely Lactobacillus and Alistipes, that could be implicated in the management of endothelial and inflammatory dysfunctions associated with CVD, and to unravel the role of nutrition in the modulation of those bacteria.

A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity.

Western lifestyle is linked to autoimmune and metabolic diseases, driven by changes in diet and gut microbiota composition. Using Toll-like receptor 7 (TLR7)-dependent mouse models of systemic lupus erythematosus (SLE), we dissect dietary effects on the gut microbiota and find that Lactobacillus reuteri can drive autoimmunity but is ameliorated by dietary resistant starch (RS). Culture of internal organs and 16S rDNA sequencing revealed TLR7-dependent translocation of L. reuteri in mice and fecal enrichment of Lactobacillus in a subset of SLE patients. L. reuteri colonization worsened autoimmune manifestations under specific-pathogen-free and gnotobiotic conditions, notably increasing plasmacytoid dendritic cells (pDCs) and interferon signaling. However, RS suppressed the abundance and translocation of L. reuteri via short-chain fatty acids, which inhibited its growth. Additionally, RS decreased pDCs, interferon pathways, organ involvement, and mortality. Thus, RS exerts beneficial effects in lupus-prone hosts through suppressing a pathobiont that promotes interferon pathways implicated in the pathogenesis of human autoimmunity.