Short-chain fatty acid levels in stools of patients with inflammatory bowel disease are lower than those in healthy subjects.

OBJECTIVE: Short-chain fatty acids (SCFAs) are produced when the microbiota in the large intestine cause fermentation of dietary carbohydrates and fibers. These fatty acids constitute the primary energy source of colon mucosa cells and have a protective effect in patients suffering from inflammatory bowel disease (IBD). This study aimed to compare the SCFA levels in the stools of patients with IBD and healthy controls. METHOD: Healthy controls and patients with IBD aged 18 and over were included in the study. Stool samples from all patients and healthy controls were collected, and stool acetic acid, propionic acid, and butyric acid levels were measured using a gas chromatography-mass spectrometry measurement method. RESULTS: In this study, 64 participants were divided into two groups: 34 were in IBD (Crohn disease and ulcerative colitis) and 30 were in healthy control group. When fecal SCFA concentrations of IBD and healthy control groups were compared, a statistically significant difference was observed between them. When the fecal SCFA concentrations of Crohn's disease and ulcerative colitis patients in the IBD group were compared, however, no statistically significant difference was observed between them. Furthermore, when the participants' diet type (carbohydrate-based, vegetable-protein-based and mixed diet) and the number of meals were compared with fecal SCFA concentrations, no statistically significant difference was observed between them. CONCLUSION: In general, fecal SCFA levels in patients with IBD were lower than those in healthy controls. Moreover, diet type and the number of meals had no effect on stool SCFA levels in patients with IBD and healthy individuals.

Acetate derived from the intestinal tract has a critical role in maintaining skeletal muscle mass and strength in mice.

Acetate is a short-chain fatty acid (SCFA) that is produced by microbiota in the intestinal tract. It is an important nutrient for the intestinal epithelium, but also has a high plasma concentration and is used in the various tissues. Acetate is involved in endurance exercise, but its role in resistance exercise remains unclear. To investigate this, mice were administered either multiple antibiotics with and without oral acetate supplementation or fed a low-fiber diet. Antibiotic treatment for 2 weeks significantly reduced grip strength and the cross-sectional area (CSA) of muscle fiber compared with the control group. Intestinal concentrations of SCFAs were reduced in the antibiotic-treated group. Oral administration of acetate with antibiotics prevented antibiotic-induced weakness of skeletal muscle and reduced CSA of muscle fiber. Similarly, a low-fiber diet for 1 year significantly reduced the CSA of muscle fiber and fecal and plasma acetate concentrations. To investigate the role of acetate as an energy source, acetyl-CoA synthase 2 knockout mice were used. These mice had a shorter lifespan, reduced skeletal muscle mass and smaller CSA of muscle fiber than their wild type littermates. In conclusion, acetate derived from the intestinal microbiome can contribute to maintaining skeletal muscle performance.

Archaea influence composition of endoscopically visible ileocolonic biofilms.

The gut microbiota has been implicated as a driver of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Recently we described, mucosal biofilms, signifying alterations in microbiota composition and bile acid (BA) metabolism in IBS and ulcerative colitis (UC). Luminal oxygen concentration is a key factor in the gastrointestinal (GI) ecosystem and might be increased in IBS and UC. Here we analyzed the role of archaea as a marker for hypoxia in mucosal biofilms and GI homeostasis. The effects of archaea on microbiome composition and metabolites were analyzed via amplicon sequencing and untargeted metabolomics in 154 stool samples of IBS-, UC-patients and controls. Mucosal biofilms were collected in a subset of patients and examined for their bacterial, fungal and archaeal composition. Absence of archaea, specifically Methanobrevibacter, correlated with disrupted GI homeostasis including decreased microbial diversity, overgrowth of facultative anaerobes and conjugated secondary BA. IBS-D/-M was associated with absence of archaea. Presence of Methanobrevibacter correlated with Oscillospiraceae and epithelial short chain fatty acid metabolism and decreased levels of Ruminococcus gnavus. Absence of fecal Methanobrevibacter may indicate a less hypoxic GI environment, reduced fatty acid oxidation, overgrowth of facultative anaerobes and disrupted BA deconjugation. Archaea and Ruminococcus gnavus could distinguish distinct subtypes of mucosal biofilms. Further research on the connection between archaea, mucosal biofilms and small intestinal bacterial overgrowth should be performed.

Gut microbiome and cardiometabolic comorbidities in people living with HIV.

BACKGROUND: Despite modern antiretroviral therapy (ART), people living with HIV (PLWH) have increased relative risk of inflammatory-driven comorbidities, including cardiovascular disease (CVD). The gut microbiome could be one of several driving factors, along with traditional risk factors and HIV-related risk factors such as coinfections, ART toxicity, and past immunodeficiency. RESULTS: PLWH have an altered gut microbiome, even after adjustment for known confounding factors including sexual preference. The HIV-related microbiome has been associated with cardiometabolic comorbidities, and shares features with CVD-related microbiota profiles, in particular reduced capacity for short-chain fatty acid (SCFA) generation. Substantial inter-individual variation has so far been an obstacle for applying microbiota profiles for risk stratification. This review covers updated knowledge and recent advances in our understanding of the gut microbiome and comorbidities in PLWH, with specific focus on cardiometabolic comorbidities and inflammation. It covers a comprehensive overview of HIV-related and comorbidity-related dysbiosis, microbial translocation, and microbiota-derived metabolites. It also contains recent data from studies in PLWH on circulating metabolites related to comorbidities and underlying gut microbiota alterations, including circulating levels of the SCFA propionate, the histidine-analogue imidazole propionate, and the protective metabolite indole-3-propionic acid. CONCLUSIONS: Despite recent advances, the gut microbiome and related metabolites are not yet established as biomarkers or therapeutic targets. The review gives directions for future research needed to advance the field into clinical practice, including promises and pitfalls for precision medicine. Video Abstract.

Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions.

BACKGROUND: Gut microbiota (GM) have been implicated as important regulators of gastrointestinal symptom which is commonly occurred along with respiratory influenza A virus (IAV) infection, suggesting the involvement of the gut-to-lung axis in a host's response to IAV. IAV primarily destroys airway epithelium tight junctions (TJs) and consequently causes acute respiratory disease syndrome. It is known that GM and their metabolism produce an anti-influenza effect, but their role in IAV-induced airway epithelial integrity remains unknown. METHODS: A mouse model of IAV infection was established. GM were analyzed using 16S rRNA gene sequencing, and short-chain fatty acids (SCFAs) levels were measured. GM depletion and fecal microbiota transplantation (FMT) were conducted to validate the role of GM in IAV infection. A pair-feeding experiment was conducted to reveal whether IAV-induced GM dysbiosis is attributed to impaired food intake. Furthermore, human bronchial epithelial (HBE) cells were cocultured with IAV in the presence or absence of acetate. TJs function was analyzed by paracellular permeability and transepithelial electronic resistance (TEER). The mechanism of how acetate affects TJs integrity was evaluated in HBE cells transfected with G protein-coupled receptor 43 (GPR43) short hairpin RNA (shRNA). RESULTS: IAV-infected mice exhibited lower relative abundance of acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) and decreased acetate levels in gut and serum. These changes were partly caused by a decrease in food consumption (due to anorexia). GM depletion exacerbated and FMT restored IAV-induced lung inflammatory injury. IAV infection suppressed expressions of TJs (occludin, ZO-1) leading to disrupted airway epithelial barrier function as evidenced by decreased TEER and increased permeability. Acetate pretreatment activated GPR43, partially restored IAV-induced airway epithelial barrier function, and reduced inflammatory cytokines levels (TNF-α, IL-6, and IL-1ß). Such protective effects of acetate were absent in HBE cells transfected with GPR43 shRNA. Acetate and GPR43 improved TJs in an AMP-activated protein kinase (AMPK)-dependent manner. CONCLUSION: Collectively, our results demonstrated that GM protected airway TJs by modulating GPR43-AMPK signaling in IAV-induced lung injury. Therefore, improving GM dysbiosis may be a potential therapeutic target for patients with IAV infection.

Enhanced medium-chain fatty acid production from sewage sludge by combined electro-fermentation and anaerobic fermentation.

Electro-fermentation (EF) was combined with anaerobic fermentation (AF) to promote medium-chain fatty acid (MCFA) from sewage sludge. Results showed that EF at acidification process significantly increased short-chain fatty acid (SCFA) production of by 0.5 times (82.4 mmol C/L). AF facilitated the chain elongation (CE) process by enhancing the SCFA conversion. Combined EF at acidification and AF at CE (EF-AF) achieved the highest MCFA production of 27.9 mmol C/L, which was 20 %-866 % higher than the other groups. Electrochemical analyses showed that enhanced SCFA and MCFA production was accompanied with good electrochemical performance at acidification and CE. Microbial analyses showed that EF-AF promoted MCFA production by enriching electrochemically active bacteria (EAB, Bacillus sp.). Enzyme analyses indicated that EF-AF promoted MCFA production by enriching the functional enzymes involved in Acetyl-CoA formation and the fatty acid biosynthesis (FAB) pathway. This study provided new insights into the production of MCFA from enhanced sewage sludge.

A graminan type fructan from Achyranthes bidentata prevents the kidney injury in diabetic mice by regulating gut microbiota.

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease, and few therapeutic options are available. The root of Achyranthis bidentatae (AB) is commonly used for DKD treatment in Traditional Chinese medicine. However, its mechanisms are still unclear. Here, a graminan type fructan ABPW1 with molecular weight of 3998 Da was purified from AB. It was composed of ß-1,2-linked Fruf, ß-2,6-linked-Fruf and ß-1,2,6-linked-Fruf backbone, and terminated with T-Glcp and 2-Fruf residues. ABPW1 protected against kidney injuries and intestinal barrier disruption in Streptozotocin (STZ)/High fat diet (HFD) mice. It could modulate gut microbiota composition, evidenced by a rise in the abundance of Bacteroide and decreases of Rikenella, Alistipes, Laedolimicola and Faecalibaculum. ABPW1 intervention promoted short chain fatty acids (SCFAs) production in STZ/HFD mice, especially propionate and isobutyric acid. Antibiotic treatment further demonstrated the key role of gut microbiota in the renal protective action of ABPW1. In addition, in vitro simulated digestion and fermentation together with in vivo fluorescent labeling studies demonstrated ABPW1 was indigestible in upper digestive tract but could reach the colon and be degraded into SCFAs by gut microbiota there. Overall, these data suggested ABPW1 has the potential application on DKD prevention.

Exploring the interaction and impact of probiotic and commensal bacteria on vitamins, minerals and short chain fatty acids metabolism.

There is increasing evidence that probiotic and commensal bacteria play a role in substrate metabolism, energy harvesting and intestinal homeostasis, and may exert immunomodulatory activities on human health. In addition, recent research suggests that these microorganisms interact with vitamins and minerals, promoting intestinal and metabolic well-being while producing vital microbial metabolites such as short-chain fatty acids (SCFAs). In this regard, there is a flourishing field exploring the intricate dynamics between vitamins, minerals, SCFAs, and commensal/probiotic interactions. In this review, we summarize some of the major hypotheses beyond the mechanisms by which commensals/probiotics impact gut health and their additional effects on the absorption and metabolism of vitamins, minerals, and SCFAs. Our analysis includes comprehensive review of existing evidence from preclinical and clinical studies, with particular focus on the potential interaction between commensals/probiotics and micronutrients. Finally, we highlight knowledge gaps and outline directions for future research in this evolving field.

[Effects of acupuncture on fecal short-chain fatty acids and TLR4/MyD88/NF-κB signaling pathway in spontaneously hypertensive rats].

OBJECTIVE: To observe the effects of acupuncture on blood pressure, fecal short-chain fatty acids (SCFAs) and toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway in spontaneously hypertensive rats (SHR), and to explore the mechanism of acupuncture for anti-hypertension. METHODS: Twenty-four male SHR of SPF grade were randomly divided into a model group, a western medication group, an acupuncture group and a sham acupuncture group, with 6 rats in each group, and 6 male Wistar-Kyoto rats were selected as the blank group additionally. Hydrochlorothiazide solution was given by gavage in the western medication group; acupuncture was applied at bilateral "Renying" (ST 9) and "Zusanli" (ST 36) in the acupuncture group, 20 min a time; acupuncture was applied at the non-meridian and non-acupoint points close to bilateral "Renying" (ST 9) and "Zusanli" (ST 36) in the sham acupuncture group, 20 min a time. The intervention was adopted once a day for 4 weeks continuously in each group. The systolic blood pressure (SBP) of the caudal artery was measured before intervention and after 1, 2, 3 and 4 weeks of intervention. After intervention, the morphology of colonic tissue was observed by HE staining; the fecal level of SCFAs was detected by gas chromatography; the serum levels of interleukin (IL)-6, IL-1ßand tumor necrosis factor-α (TNF-α) were detected by ELISA; the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was detected by Western blot. RESULTS: Compared with the blank group, in the model group, the SBP was increased (P<0.05), significant pathological changes could be found in the colonic tissue, the fecal SCFAs level was decreased (P<0.05), the serum levels of IL-6, IL-1ß and TNF-α were increased (P<0.05), the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was increased (P<0.05). Compared with the model group, the SBP after 2, 3 and 4 weeks of intervention was decreased (P<0.05), the serum levels of IL-6, IL-1ß and TNF-α were decreased (P<0.05) in the acupuncture group and the western medication group; the mucosal epithelium of colonic tissue was intact, the number of intestinal glands was abundant, the fecal SCFAs level was increased (P<0.05), and the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was decreased (P<0.05) in the acupuncture group. Compared with the sham acupuncture group, the SBP after 2, 3 and 4 weeks of intervention was decreased (P<0.05), the fecal SCFAs level was increased (P<0.05), the serum levels of IL-6, IL-1ß and TNF-α were decreased (P<0.05), the protein expression of TLR4, MyD88 and NF-κB p65 in the mesenteric artery was decreased (P<0.05) in the acupuncture group. CONCLUSION: Acupuncture at bilateral "Renying" (ST 9) and "Zusanli" (ST 36) can effectively play an anti-hypertensive role in SHR. Its mechanism may be related to regulating fecal SCFAs level and inhibiting the TLR4/MyD88/NF-κB signaling pathway.

Chlorogenic Acid/Linoleic Acid-Fortified Wheat-Resistant Starch Ameliorates High-Fat Diet-Induced Gut Barrier Damage by Modulating Gut Metabolism.

This study aimed to investigate alterations in gut microbiota and metabolites mediated by wheat-resistant starch and its repair of gut barrier dysfunction induced by a high-fat diet (HFD). Structural data revealed that chlorogenic acid (CA)/linoleic acid (LA) functioned through noncovalent interactions to form a more ordered structure and fortify antidigestibility in wheat starch (WS)-CA/LA complexes; the resistant starch (RS) contents of WS-CA, WS-LA, and WS-CA-LA complexes were 23.40 ± 1.56%, 21.25 ± 1.87%, and 35.47 ± 2.16%, respectively. Dietary intervention with WS-CA/LA complexes effectively suppressed detrimental alterations in colon tissue morphology induced by HFD and repaired the gut barrier in ZO-1 and MUC-2 levels. WS-CA/LA complexes could augment gut barrier-promoting microbes including Parabacteroides, Bacteroides, and Muribaculum, accompanied by an increase in short-chain fatty acids (SCFAs) and elevated expression of SCFA receptors. Moreover, WS-CA/LA complexes modulated secondary bile acid metabolism by decreasing taurochenodeoxycholic, cholic, and deoxycholic acids, leading to the activation of bile acid receptors. Collectively, this study offered guiding significance in the manufacture of functional diets for a weak gut barrier.

Isobutyric acid enhances the anti-tumour effect of anti-PD-1 antibody.

The low response rate of immune checkpoint inhibitors (ICIs) is a challenge. The efficacy of ICIs is influenced by the tumour microenvironment, which is controlled by the gut microbiota. In particular, intestinal bacteria and their metabolites, such as short chain fatty acids (SCFAs), are important regulators of cancer immunity; however, our knowledge on the effects of individual SCFAs remains limited. Here, we show that isobutyric acid has the strongest effect among SCFAs on both immune activity and tumour growth. In vitro, cancer cell numbers were suppressed by approximately 75% in humans and mice compared with those in controls. Oral administration of isobutyric acid to carcinoma-bearing mice enhanced the effect of anti-PD-1 immunotherapy, reducing tumour volume by approximately 80% and 60% compared with those in the control group and anti-PD-1 antibody alone group, respectively. Taken together, these findings may support the development of novel cancer therapies that can improve the response rate to ICIs.

Sea Buckthorn Polysaccharide Ameliorates Colitis.

Ulcerative colitis (UC) is characterized by chronic inflammation and ulceration of the intestinal inner lining, resulting in various symptoms. Sea buckthorn berries contain a bioactive compound known as sea buckthorn polysaccharide (SBP). However, the precise mechanisms underlying the impact of SBP on UC remain unclear. In this study, we investigated the effects of pretreatment with SBP on colitis induced by DSS. Our findings demonstrate that SBP pretreatment effectively reduces inflammation, oxidative stress, and intestinal barrier damage associated with colitis. To further elucidate the role of SBP-modulated gut microbiota in UC, we performed fecal microbiota transplantation (FMT) on DSS-treated mice. The microbiota from SBP-treated mice exhibits notable anti-inflammatory and antioxidant effects, improves colonic barrier integrity, and increases the abundance of beneficial bacteria, as well as enhancing SCFA production. Collectively, these results strongly indicate that SBP-mediated amelioration of colitis is attributed to its impact on the gut microbiota, particularly through the promotion of SCFA-producing bacteria and subsequent elevation of SCFA levels. This study provides compelling evidence supporting the efficacy of pre-emptive SBP supplementation in alleviating colitis symptoms by modulating the gut microbiota, thereby offering novel insights into the potential of SBP as a regulator of the gut microbiota for colitis relief.

Impact of a Whole-Food, High-Soluble Fiber Diet on the Gut-Muscle Axis in Aged Mice.

Previous studies have identified a role for the gut microbiome and its metabolic products, short-chain fatty acids (SCFAs), in the maintenance of muscle mass and physical function (i.e., the gut-muscle axis), but interventions aimed at positively impacting the gut-muscle axis during aging are sparse. Gut bacteria ferment soluble fiber into SCFAs, and accordingly, to evaluate the impact of a high-soluble-fiber diet (HSFD) on the gut-muscle axis, we fed a whole-food, 3×-higher-soluble fiber-containing diet (relative to standard chow) to aged (98 weeks) C57BL/6J mice for 10 weeks. The HSFD significantly altered gut bacterial community structure and composition, but plasma SCFAs were not different, and a positive impact on muscle-related measures (when normalized to body weight) was not identified. However, when evaluating sex differences between dietary groups, female (but not male) HSFD-fed mice had significant increases for SCFAs, the quadriceps/body weight (BW) ratio, and treadmill work performance (distance run × BW), which suggests that an HSFD can positively impact the gut-muscle axis. In contrast, consistent effects in both male and female HSFD-fed mice included weight and fat loss, which suggests a positive role for an HSFD on the gut-adipose axis in aged mice.

Nano-Selenium Alleviates Cd-Induced Chronic Colitis through Intestinal Flora.

BACKGROUND: Cadmium (Cd) is an environmental contaminant that poses risks to human and animal health. Selenium (Se), a beneficial element, alleviates the detrimental consequences of colitis and Cd toxicity. Se is found in food products as both inorganic Se (sodium selenite) and organic Se (typically Se-enriched yeast). Nano-selenium (nano-Se; a novel form of Se produced through the bioreduction of Se species) has recently garnered considerable interest, although its effects against Cd-induced enterotoxicity are poorly understood. The aim of this study was to investigate the impact of nano-selenium on mitigating cadmium toxicity and safeguarding the integrity of the intestinal barrier. METHODS: For a total of two cycles, we subjected 6-week-old C57 mice to chronic colitis by exposing them to Cd and nano-selenium for two weeks, followed by DSS water for one week. RESULTS: The application of nano-selenium mitigated the intensity of colitis and alleviated inflammation in the colon. Nano-selenium enhanced the diversity of the intestinal flora, elevated the concentration of short-chain fatty acids (SCFAs) in feces, and improved the integrity of the intestinal barrier. CONCLUSIONS: In summary, nano-Se may reduce intestinal inflammation by regulating the growth of intestinal microorganisms and protecting the intestinal barrier.

Targeting Non-Alcoholic Fatty Liver Disease with Hawthorn Ethanol Extract (HEE): A Comprehensive Examination of Hepatic Lipid Reduction and Gut Microbiota Modulation.

Recent studies have highlighted the lipid-lowering ability of hawthorn ethanol extract (HEE) and the role played by gut flora in the efficacy of HEE. Our study sought to explore the effects of HEE on non-alcoholic fatty liver disease (NAFLD) in normal flora and pseudo germ-free mice. The results showed that HEE effectively diminished hepatic lipid accumulation, ameliorated liver function, reduced inflammatory cytokine levels and blood lipid profiles, and regulated blood glucose levels. HEE facilitated triglyceride breakdown, suppressed fatty acid synthesis, and enhanced intestinal health by modulating the diversity of the gut microbiota and the production of short-chain fatty acids in the gut. In addition, HEE apparently helps to increase the presence of beneficial genera of bacteria, thereby influencing the composition of the gut microbiota, and the absence of gut flora affects the efficacy of HEE. These findings reveal the potential of hawthorn for the prevention and treatment of NAFLD and provide new perspectives on the study of functional plants to improve liver health.

Fermented dietary fiber from soy sauce residue exerts antidiabetic effects through regulating the PI3K/AKT signaling pathway and gut microbiota-SCFAs-GPRs axis in type 2 diabetic mellitus mice.

The gut plays a crucial role in the development and progression of metabolic disorders, particularly in relation to type 2 diabetes mellitus (T2DM). While a high intake of dietary fiber is inversely associated with the risk of T2DM, the specific effects of various dietary fibers on T2DM are not fully understood. This study investigated the anti-diabetic properties of fermented dietary fiber (FDF) derived from soy sauce residue in T2DM mice, demonstrating its ability to lower blood glucose levels and ameliorate insulin resistance. Our findings revealed that FDF could enhance hepatic glucose metabolism via the IRS-1/PI3K/AKT/mTOR pathway. Additionally, the anti-diabetic effect of FDF was correlated with alterations in gut microbiota composition in T2DM mice, promoting a healthier gut environment. Specifically, FDF increased the abundance of beneficial flora such as Dubosiella, Butyricimonas, Lachnospiraceae_NK4A136_group, Lactobacillus and Osillibacter, while reducing harmful bacteria including Bilophila, Parabacteroides and Enterorhabdus. Further analysis of microbial metabolites, including short-chain fatty acids (SCFAs) and bile acids (BAs), provided evidence of FDF's regulatory effects on cecal contents in T2DM mice. Importantly, FDF treatment significantly restored the G-protein-coupled receptors (GPRs) expression in the colon of T2DM mice. In conclusion, our study suggests that the anti-diabetic effects of FDF are associated with the regulation of both the liver-gut axis and the gut microbiota-SCFAs-GPRs axis.

Comparative analysis of short-chain fatty acid levels in non-alcoholic steatohepatitis rat model: Impact of high-fat high-fructose (HFHF), high fat, and Western diets.

The evidence on the role of diets in the production of short-chain fatty acids (SCFAs) was limited. The aim of this study was to assess the potential effects of high-fat high-fructose (HFHF), high-fat, and Western diets on the levels of SCFA. A research experiment employing a post-test-only control group design was carried out from January to April 2022. A total of 27 rats were randomly allocated to each study group. SCFA was measured two weeks after diet administration. Analysis of variance (ANOVA) test was used to analyze the differences among groups, and the effect estimate of each group was analyzed using post hoc Tukey. The concentrations of SCFAs post HFHF diets were recorded as follows: acetic acid at 54.60±10.58 mmol/g, propionic acid at 28.03±8.81 mmol/g, and butyric acid at 4.23±1.68 mmol/g. Following the high-fat diet, acetic acid measured 61.85±14.25 mmol/gr, propionic acid measured 25.19±5.55 mmol/gr, and butyric acid measured 6.10±2.93 mmol/gr. After the administration of Western diet, the levels of SCFA were 68.18±25.73, 29.69±12.76, and 7.48±5.51 mmol/g for acetic acid, propionic acid, and butyric acid, respectively. The level of butyric acid was significantly lower in HFHF diet group compared to the normal diet (mean difference (MD) 6.34; 95%CI: 0.61, 12.04; p=0.026). The levels of acetic acid (p=0.419) and propionic acid (p=0.316) were not statistically different among diet types (HFHF, high-fat, and Western diet). In conclusion, HFHF diet is associated with a lower level of butyric acid than the normal diet in a rat model.

Identification of carbohydrate gene clusters obtained from in vitro fermentations as predictive biomarkers of prebiotic responses.

BACKGROUND: Prebiotic fibers are non-digestible substrates that modulate the gut microbiome by promoting expansion of microbes having the genetic and physiological potential to utilize those molecules. Although several prebiotic substrates have been consistently shown to provide health benefits in human clinical trials, responder and non-responder phenotypes are often reported. These observations had led to interest in identifying, a priori, prebiotic responders and non-responders as a basis for personalized nutrition. In this study, we conducted in vitro fecal enrichments and applied shotgun metagenomics and machine learning tools to identify microbial gene signatures from adult subjects that could be used to predict prebiotic responders and non-responders. RESULTS: Using short chain fatty acids as a targeted response, we identified genetic features, consisting of carbohydrate active enzymes, transcription factors and sugar transporters, from metagenomic sequencing of in vitro fermentations for three prebiotic substrates: xylooligosacharides, fructooligosacharides, and inulin. A machine learning approach was then used to select substrate-specific gene signatures as predictive features. These features were found to be predictive for XOS responders with respect to SCFA production in an in vivo trial. CONCLUSIONS: Our results confirm the bifidogenic effect of commonly used prebiotic substrates along with inter-individual microbial responses towards these substrates. We successfully trained classifiers for the prediction of prebiotic responders towards XOS and inulin with robust accuracy (≥ AUC 0.9) and demonstrated its utility in a human feeding trial. Overall, the findings from this study highlight the practical implementation of pre-intervention targeted profiling of individual microbiomes to stratify responders and non-responders.

Mutualistic interactions of lactate-producing lactobacilli and lactate-utilizing Veillonella dispar: Lactate and glutamate cross-feeding for the enhanced growth and short-chain fatty acid production.

The human gut hosts numerous ecological niches for microbe-microbe and host-microbe interactions. Gut lactate homeostasis in humans is crucial and relies on various bacteria. Veillonella spp., gut lactate-utilizing bacteria, and lactate-producing bacteria were frequently co-isolated. A recent clinical trial has revealed that lactate-producing bacteria in humans cross-feed lactate to Veillonella spp.; however, their interspecies interaction mechanisms remain unclear. Veillonella dispar, an obligate anaerobe commonly found in the human gut and oral cavity, ferments lactate into acetate and propionate. In our study, we investigated the interaction between V. dispar ATCC 17748T and three representative phylogenetically distant strains of lactic acid bacteria, Lactobacillus acidophilus ATCC 4356T, Lacticaseibacillus paracasei subsp. paracasei ATCC 27216T, and Lactiplantibacillus plantarum ATCC 10241. Bacterial growth, viability, metabolism and gene level adaptations during bacterial interaction were examined. V. dispar exhibited the highest degree of mutualism with L. acidophilus. During co-culture of V. dispar with L. acidophilus, both bacteria exhibited enhanced growth and increased viability. V. dispar demonstrated an upregulation of amino acid biosynthesis pathways and the aspartate catabolic pathway. L. acidophilus also showed a considerable number of upregulated genes related to growth and lactate fermentation. Our results support that V. dispar is able to enhance the fermentative capability of L. acidophilus by presumably consuming the produced lactate, and that L. acidophilus cross-feed not only lactate, but also glutamate, to V. dispar during co-culture. The cross-fed glutamate enters the central carbon metabolism in V. dispar. These findings highlight an intricate metabolic relationship characterized by cross-feeding of lactate and glutamate in parallel with considerable gene regulation within both L. acidophilus (lactate-producing) and V. dispar (lactate-utilizing). The mechanisms of mutualistic interactions between a traditional probiotic bacterium and a potential next-generation probiotic bacterium were elucidated in the production of short-chain fatty acids.

Two Enterococcus faecium Isolates Demonstrated Modulating Effects on the Dysbiosis of Mice Gut Microbiota Induced by Antibiotic Treatment.

Broad-spectrum antibiotics are frequently used to treat bacteria-induced infections, but the overuse of antibiotics may induce the gut microbiota dysbiosis and disrupt gastrointestinal tract function. Probiotics can be applied to restore disturbed gut microbiota and repair abnormal intestinal metabolism. In the present study, two strains of Enterococcus faecium (named DC-K7 and DC-K9) were isolated and characterized from the fecal samples of infant dogs. The genomic features of E. faecium DC-K7 and DC-K9 were analyzed, the carbohydrate-active enzyme (CAZyme)-encoding genes were predicted, and their abilities to produce short-chain fatty acids (SCFAs) were investigated. The bacteriocin-encoding genes in the genome sequences of E. faecium DC-K7 and DC-K9 were analyzed, and the gene cluster of Enterolysin-A, which encoded a 401-amino-acid peptide, was predicted. Moreover, the modulating effects of E. faecium DC-K7 and DC-K9 on the gut microbiota dysbiosis induced by antibiotics were analyzed. The current results demonstrated that oral administrations of E. faecium DC-K7 and DC-K9 could enhance the relative abundances of beneficial microbes and decrease the relative abundances of harmful microbes. Therefore, the isolated E. faecium DC-K7 and DC-K9 were proven to be able to alter the gut microbiota dysbiosis induced by antibiotic treatment.