This study may provide data basis for the effective application of butyric acid-producing bacteria or butyric acid in high-starch diet. Figure 9. Mechanism by which different contents of gelatinized starch diet influence the gut health. High gelatinized starch diets cause gut microbial changes and lipid metabolism disorders, which further leads to inflammation.

However, the moderate amount of gelatinized starch in diets is beneficial to the health of gut Figure 9A. The health of gut is largely determined by the acidity and alkalinity of gut environment Kohl et al. Previous study has reported that in an alkaline environment, the abundance of beneficial bacteria, such as lactic acid bacteria, was decreased, that of harmful bacteria was increased, resulting in gut immune function decline Jeurissen et al.

In this experiment, moderate gelatinized starch diets caused an increase in gut microbiota diversity relative to control group, and the relative abundance of many beneficial bacteria was significantly improved relative to control group at genera level, including Lactococcus , Lactobacillus , Geobacillus , Clostridium , Bifidobacterium , and so on.

We also found that the pH of gut chyme was decreased significantly and lactic acid content was increased significantly in C10 group, with the increase in relative abundance of Lactobacilli and Bifidobacteria. Thus, a weakly acidic environment occurred in gut, which in turn promoted the growth of beneficial bacteria and the formation of a virtuous circle Sissons, In such a good environment, gut wall thickness and villus length was increased, and the gut absorption surface area was expanded, which was beneficial to the nutrient absorption in gut Sissons, According to the predictive functional profiles of microbial communities determined by PICRUSt analysis, the top ten most abundant functions were shown in Figure 5 , and the obvious differences in level 3 KEGG pathways were observed among the three groups Table 4.

Membrane transport pathways, such as transporters and ABC transporters, are essential for cell survival and growth and crucial for the survival of microbiota in gut ecosystem Lyons et al.

The research demonstrated that such predicted transporter functions were connected with nutrient-associated changes in gut microbiota composition Odamaki et al. In this experiment, the proportion of transporters was significantly increased in moderate gelatinized starch diet group, while this change was reversed in the high gelatinized starch diet group.

This indicated that the addition of gelatinized starch to diet was important for the changes in the microbiota of gut, and that the addition of an appropriate amount of gelatinized starch was beneficial to gut microbiota, enabling the microbial community to utilize the nutrients better in gut by enhancing membrane transport pathways.

The level of energy metabolism and metabolism of cofactors and vitamins in gut microbiota are related to the growth of gut microbiota and the state of body. One previous study has shown that high-grain diets lead to gut inflammation and dramatical increase in energy metabolism pathway levels of gut microbiota in goats Zhang et al.

Another study has reported that energy metabolic pathways in gut microbiota were significantly increased in spring samples, which could facilitate a Tibetan Macaques Macaca thibetana recovery from acute energy loss experienced during winter Sun et al. In addition, the metabolism level of cofactors and vitamins in late-instar Spodoptera littoralis in gut microbiota was significantly higher than that in the early instar larva Chen et al.

These studies suggested that gut microbiota might respond to stimuli from the inside or outside of the body by significantly increasing energy metabolism and the metabolism of coenzyme factors and vitamins. Our results further demonstrate that microbiota play a key role in the gut damage caused by the high-carbohydrate diet.

Our findings make the targeted regulation of gut microbiota possible to mitigate the damage caused by the increase in starch content in feed of fish. In summary, we demonstrate that ordinary dietary gelatinized starch significantly alters gut microbiota composition in Chinese perch.

Furthermore, this study makes the first comprehensive illustration of the action mechanisms and the specific regulatory effects of high carbohydrate diet-modulated microbiota on gut health of non-mammals.

Our results reveal that Mycoplasma and butyric acid-producing bacteria play a key role in the above process. The datasets presented in this study can be found in online repositories.

The animal study was reviewed and approved by the Ethics Committee of the Institute of Laboratory Animal Centre, Huazhong Agriculture University. YZ, X-FL, and SH designed the experiments and helped to draft the manuscript. YZ, XC, JW, JL, QZ, ZZ, LL, and MA performed the experiments.

All authors read and approved the final manuscript. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Asaduzzaman, M. Effects of carbohydrate source for maintaining a high C: N ratio and fish driven re-suspension on pond ecology and production in periphyton-based freshwater prawn culture systems.

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Washington DC: The National Academies Press, — Odamaki, T. Jennifer Chesak is a Nashville-based freelance book editor and writing instructor. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available.

Carbs get a bad rap, but numerous healthy foods contain carbs. Here are 12 high carb foods that are incredibly healthy. This is a detailed guide to healthy low carb eating for people with diabetes.

Low carb diets are effective against both type 1 and type 2 diabetes. While they're not typically able to prescribe, nutritionists can still benefits your overall health.

Let's look at benefits, limitations, and more. A new study found that healthy lifestyle choices — including being physically active, eating well, avoiding smoking and limiting alcohol consumption —….

Carb counting is complicated. Take the quiz and test your knowledge! Together with her husband, Kansas City Chiefs MVP quarterback Patrick Mahomes, Brittany Mohomes shares how she parents two children with severe food…. While there are many FDA-approved emulsifiers, European associations have marked them as being of possible concern.

Let's look deeper:. Researchers have found that a daily multivitamin supplement was linked with slowed cognitive aging and improved memory.

Dietitians can help you create a more balanced diet or a specialized one for a variety of conditions. We look at their benefits and limitations. Liquid collagen supplements might be able to reduce some effects of aging, but research is ongoing and and there may be side effects.

A Quiz for Teens Are You a Workaholic? How Well Do You Sleep? Health Conditions Discover Plan Connect. The No BS Guide to Good, Healthy Carbs. Medically reviewed by Katherine Marengo LDN, R.

Types of carbs Two rules to carb choices Carbs and blood sugar Carbs and your brain Carb obsession explained Takeaway Carbs are the main source of energy for your body. Share on Pinterest. We need carbs to: energize us deliver vitamins and minerals provide fiber for fullness and regularity improve gut health help cognitive function.

Was this helpful? Simple vs. What are simple carbohydrates? table sugar brown sugar glucose sucrose high fructose corn syrup honey agave milk lactose fruit fructose. Complex carbohydrates whole fruit vegetables nuts legumes whole grains whole wheat products. A simple two-step carb strategy.

Why does blood sugar matter? Antibiotics kill off all the bacteria in your gut — good and bad — so diversifying and building up your gut bacteria is important.

Prebiotics are what keep your gut bacteria healthy and fed. All prebiotic foods contain fiber, but not all fibers are prebiotics. There are specific foods with just the right kind of fiber that makes it a prebiotic. Your gut health is not only important for digestive regularity i.

helping you poop , but it can also affect your overall physical and mental health, and influence your risk for chronic disease, according to Harvard Medical School. You might not automatically think of asparagus as a carb, but as it turns out, the veggie has a specific type of carb that is super beneficial to your gut health.

The inulin fiber in asparagus "has been associated with healthy digestion and the production of beneficial bacteria," says Jeanette Kimszal, RD. Asparagus is a favorite gut health food of hers due to its health benefits and versatility in cooking.

Inulin is a type of carb that's created by plants, and it's not digested by the body. Rather, it serves as the "food" for the good probiotic bacteria in your gut, which makes it a great nutrient for digestive health, according to the Cleveland Clinic. That being said, fermentable inulin may cause symptoms in people with digestive conditions like irritable bowel syndrome IBS.

Potatoes are often dismissed as a healthy food option because they are high in starchy carbs, but in reality, they're full of important nutrients — especially when it comes to gut health.

Digestive health dietitian Jenna Volpe RD, LD , is a big fan of potatoes for gut health. Not only are they inexpensive, easy to digest and versatile in cooking, but "they contain resistant starch, which is a special type of prebiotic that helps feed lactobacillus and other probiotic microbes in the gut.

If you've spent any time in the kitchen lately cooking up your favorite dishes, you've probably used some onions and garlic. Onions and garlic are part of that family of prebiotic foods that have inulin, which is beneficial for your gut, per the Cleveland Clinic.

Mushrooms are super trendy right now and for good reason. They are incredibly versatile as an ingredient in multiple cuisines, and they can even serve as a plant-based meat substitute.

Many dietitians recommend eating mushrooms for gut health. Oats are another source of gut-healthy fiber. Oats are often touted for their beneficial effects on lowering cholesterol, but thanks to the beta-glucan fiber, they are also great for gut health — making them a solid choice for accomplishing multiple health goals.

If you want the most fiber benefits from your oats, it's probably best to eat your oats as opposed to drinking oat milk, Keith says. That's because some of the fiber is lost during the production of oat milk.

While low-carb eating may lead to quick weight loss , the rigidity of the plan makes it nearly impossible to stick with. No wonder keto was ranked among the worst diets of Beyond that, research suggests that super-low-carb strategies probably aren't doing other aspects of your body any favors, including your heart and your ever-important gut.

It's extremely important that we separate good carbs from bad carbs," says Will Bulsiewicz, M. And it's extremely important that we eat them, confirms Kenneth Brown, M. All three macronutrients—carbohydrates, fats and proteins—are important for our bodies and are the basic building blocks of our food and energy to fuel our body.

The healthiest eating pattern includes a balance of all three, according to Bulsiewicz. Not only are carbs our body and brain's preferred source of energy, but they also play a vital role in our gut health.

ICYMI, a healthy population of good bacteria, aka microbiome , in our gastrointestinal tract has been linked to lower risk for everything from depression and anxiety to certain cancers to heart disease.

One particular type of carb, fiber, is especially impactful in terms of our gut health … or lack thereof. These are both complex carbohydrates, and this is causing damage to our gut microbiome," Bulsiewicz says, citing a study published in the American Journal of Lifestyle Medicine.

Can we stop trashing 'carbs' as a category? Instead, Bulsiewicz and Brown agree that your goal should be to focus on fueling up with more of the right carbs that will feed your microbiome, muscles, brain and taste buds all at once. A review published in March in the journal Microorganisms confirms that carbohydrates play a large role in the short-term and long-term health of our gut microbiome overall.

That being said, carbohydrates can positively and negatively impact gut health, depending on which types of carbs you eat, Brown explains.

To optimize gut health, it's best to consume a variety of high-fiber carbs and limit intake of refined carbs or foods high in added sugar. The level of refinement with carbohydrates is critically important, Bulsiewicz adds.

Refined carbohydrates like white bread, pastries and sugar-sweetened drinks have much of their natural fiber and nutrients removed, which can trigger rapid spikes in blood sugar and may contribute to insulin resistance and other metabolic issues.

Unprocessed or minimally processed whole plant foods, however, retain their natural fiber and nutrient content, and provide more benefits for gut health than ultraprocessed items. Whenever possible, opt for the food that you could grow instead of the food developed in a lab," Bulsiewicz says.

Produce items are technically carbs, true. These always get a thumbs-up from Bulsiewicz and Brown, so consider any of your favorite fruits and veggies also part of this list.

But since we've already covered the best fruit for gut health and best vegetables for gut health , we're focusing on more classic carb sources here.

While any whole grain is great for your gut, oats stand out from the pack, according to an October review in The Journal of Nutrition. After reviewing 84 studies, oat intake was correlated with an increase in beneficial gut bacteria among those without any digestive disorder and individuals with celiac disease.

Oats offer a special kind of soluble fiber called beta-glucan that takes on a gel-like consistency in the gut and helps to keep things moving through your digestive tract, bulk up your stool and help you poop more regularly. Skip the bakery muffin and try Breakfast Blueberry-Oatmeal Cakes instead, or start your day with this trendy scrambled oats recipe.

Any kind of fermented plant food is a favorite of Bulsiewicz—and of your microbiome. Sauerkraut, kimchi, pickles, olives and tempeh "have the fiber and polyphenols to support a healthy gut microbiome, and also deliver living microbes [probiotics] that provide added benefits.

My goal is to get three to five servings of fermented food on a daily basis," he says. Tempeh, which is made from fermented soybeans that are pressed into loaf-like forms, is a particularly wise choice. Beyond offering a nice mix of protein, fat and carbs, tempeh offers an uncommon one-two punch of both prebiotics and probiotics ; two key players in boosting your gut microbiome.

After just 28 days of consuming 3½ ounces of cooked tempeh per day, participants in a February Food Research study experienced significant improvements in their overall gut health profile. Versatile, easy to sneak into everything from smoothies to salads, and nutrition all-stars all at once, this trio of omega-3 super seeds are also mainstays in Bulsiewicz's diet.

Each of them is high in fiber, omega-3 fats and protein. In other words, you are elevating all three macros in your diet when you enjoy these foods," Bulsiewicz says.

Beyond the gut-supporting fiber, the omega-3s in these seeds have been proven to produce anti-inflammatory short-chain fatty acids that may help strengthen our intestinal walls and bolster immunity, according to a December study in the International Journal of Molecular Sciences.

That same study also validates that omega-3s, like those found in seeds, can have a positive influence on the gut-brain axis; the conversation going on between our microbiomes and our brain. Snack on Homemade Multi-Seed Crackers or dive into Cocoa-Chia Pudding with Raspberries for breakfast or dessert.

Loaded with fiber and resistant starches to help fuel a healthy gut microbiome, beans and legumes "are among the healthiest foods out there," Bulsiewicz says.

Bonus: They're budget-friendly. Beans and legumes like chickpeas, black beans, kidney beans and lentils are a potent source of plant-based protein as well, Brown validates, which can help regulate blood sugar levels among other important things.

They also promote regular bowel movements, help you feel fuller for longer and support good gut bacteria," Brown says. A November review in the International Journal of Molecular Sciences found that small-but-mighty lentils deliver polyphenols and prebiotic carbs that feed our good gut bacteria in a way that can help reduce the risk for gut-related diseases.

EatingWell editors can't get enough of this Vegan Lentil Soup and Air-Fryer Stuffed Potatoes with Lentil Stew. Stop steering clear of carbs. A balanced, high-fiber diet yep, fiber is a type of carb!

can help support optimal gut health and reduce your risk for chronic diseases, Brown summarizes. An obesity-associated gut microbiome with increased capacity for energy harvest.

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Koseki, M. Furuno and H. Iwano for data discussion; and the staff at the RIKEN BioResource Research Center for providing essential materials. Kubota, 21K to H. and 22H to H. and M. Kubota and the RIKEN Junior Research Associate Program to T.

Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences IMS , Yokohama, Japan. Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kawasaki, Japan.

Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Division of Diabetes and Metabolism, The Institute for Medical Science Asahi Life Foundation, Tokyo, Japan. Department of Clinical Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition NIBIOHN , Tokyo, Japan.

Metabolome Informatics Research Team, RIKEN Center for Sustainable Resource Science CSRS , Yokohama, Japan.

Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences IMS , Yokohama, Japan. Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.

Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Tokyo, Japan. Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences IMS , Yokohama, Japan. Laboratory for Applied Regulatory Genomics Network Analysis, RIKEN Center for Integrative Medical Sciences IMS , Yokohama, Japan.

Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences IMS , Yokohama, Japan. Department of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Japan. Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences IMS , Yokohama, Japan.

Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences IMS , Yokohama, Japan. Institute for Advanced Biosciences, Keio University, Fujisawa, Japan.

Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan. Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.

Center for Epidemiology and Preventive Medicine, The University of Tokyo Hospital, Tokyo, Japan. International University of Health and Welfare, Tokyo, Japan. Department of Metabolism and Endocrinology, Tokyo Medical University Ibaraki Medical Center, Ami Town, Japan.

Laboratory for Transcriptome Technology, RIKEN Center for Integrative Medical Sciences IMS , Yokohama, Japan. Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.

Human Biology-Microbiome-Quantum Research Center WPI-Bio2Q , Keio University, Tokyo, Japan. Laboratory for Immune Cell Systems, RIKEN Center for Integrative Medical Sciences IMS , Yokohama, Japan.

You can also search for this author in PubMed Google Scholar. Kadowaki and H. conceived the project. Kubota, Y. Mizuno, N. and T. Kadowaki contributed to the enrolment of study participants and clinical data collection. and Y. processed faecal samples for metagenomics and metabolomic analyses.

performed 16S rRNA gene sequencing and metagenomic analysis. performed metabolomic analyses for hydrophilic metabolites.

performed lipidomics analyses. and P. performed CAGE analysis. and O. performed cytokine measurement and RNA extraction from PBMCs. Mochizuki prepared fundamental information tools for the analysis. Kubota and S. performed animal experiments and analysed the data. Kitami and K. analysed the omics data.

Kubota, P. and H. provided essential materials and raised funding. Kubota and H. wrote the paper together with A. Kitami and P. Correspondence to Tetsuya Kubota or Hiroshi Ohno.

are listed as the inventors on a patent regarding the metabolic effects of gut bacteria identified by a human cohort. The other authors declare no competing interests. Nature thanks Gregory Steinberg and the other, anonymous, reviewer s for their contribution to the peer review of this work.

Insulin resistance IR and metabolic syndrome MetS were the main clinical phenotypes. To evaluate the host-microbe relationship, we collected 1 host factors: clinical, plasma metabolome, peripheral blood mononuclear cells PBMC transcriptome, and cytokine data, and 2 microbial factors: 16S rRNA pyrosequencing, shotgun metagenome, and faecal metabolome.

The numbers of elements after quality filtering are shown for each data set. b , The multi-omics analysis workflow. To identify the microbes that affect metabolic phenotypes, we first analysed the phenotype-associated metabolomic signatures by binning metabolites into co-abundance groups CAGs.

Microbial signatures were determined using the 16S and metagenomic datasets, and their associations with metabolites were analysed. We also assessed the mediation effects of plasma cytokines on the relationships between faecal metabolites and metabolic markers.

The associations between clinical phenotypes and omics markers were adjusted by age and sex wherever appropriate. a , The KEGG pathway enrichment analysis of the metabolites in hydrophilic CAGs 5, 8, 12, 15, and 18, which were associated with IR in Fig. The size of disks shows the enrichment i.

b , Partial correlations between HOMA-IR and faecal levels of short-chain fatty acids SCFA such as acetate, propionate, and butyrate left panel , and disaccharides such as maltose and sucrose right panel.

Density plots indicate median and distribution. The detailed statistics are reported in Supplementary Table 5 , 6. The size and colour of the disks represent the estimate and the direction of the associations.

c , The associations between faecal glucose and arabinose and HOMA-IR as analysed in Fig. The estimates of metabolites and their P values are described.

The data were analysed with a generalized linear mixed-effect model with consent age and sex as fixed effects, and the sample collection site as a random effect. The estimate and P value are described.

The first faecal sampling for metabolomics was used to avoid redundancy. The detailed statistics are reported in Supplementary Table 9. Dots represent individual data summarized into PCo1 and PCo2. Dots represent individual data summarized into PC1 and PC2.

f , Co-abundance groups of genus-level microbes and their abundance in the participant clusters defined in Fig. The disk size represents the median abundance in the participants.

g , The co-abundance groups of genus-level microbes and their abundance in the participant clusters. The size of the disks represents overabundance to the mean in four clusters of participants determined in Fig.

The far-left column shows the genera that exhibit significant differences among the four clusters. The genera forming distinct groups in f , i. The participants were clustered into three mOTU clusters A to C based on the heatmap clustering.

The proportion of individuals with IS, intermediate, and IR are shown in the pie charts above the heatmap as Fig. Only those with significant associations with metabolic markers are depicted. The disk size and colour represent absolute values of standardized coefficient and the direction of associations.

The detailed statistics are reported in Supplementary Table j , Microbe-metabolite networks of IR- or and IS-associated co-abundance microbial groups from Fig. All faecal hydrophilic metabolites and faecal microbe-related lipid metabolites were included in the analysis.

The metabolites in CAGs relating to carbohydrates shown in Fig. k , The relative abundance of IR-associated faecal carbohydrates in the participant clusters. The metabolites significantly different among these four clusters are coloured grey in the top row.

a , b , Box plots indicate the median, upper and lower quartiles, and upper and lower extremes except for outliers. Kruskal-Wallis test g , k. See the Source Data g for exact P values. a , b , The associations between the KEGG pathways relating to amino acid metabolism a and lipid metabolism b , faecal carbohydrates, top three genera positively or negatively correlated with faecal carbohydrates in Fig.

c , The associations between representative metabolic markers and the KEGG pathways relating to carbohydrate metabolism, amino acid metabolism, lipid metabolism, and membrane transport defined in the KEGG orthology database. The pathways with significant associations with metabolic markers are included in the plots.

The far-left column shows the type of carbohydrate metabolites that each PTS gene is involved in. The far-left column shows whether the genes were predicted to function as extracellular enzymes.

g , Representative pathways in starch and sucrose metabolism KEGG pathway relating to glycosidase activities to degrade poly- and oligosaccharides into monosaccharides. i , The presence and absence of KEGG orthologues predicted to function as extracellular enzymes in 45 strains.

The strains from the top three genera positively or negatively correlated with faecal carbohydrates shown in Fig. Density plots indicate median and distribution e , h. a , Cell-type gene set enrichment analysis based on the Human Gene Atlas database using Enrichr.

Red and blue colour scales represent IR and IS-associated cell types, respectively please refer to Methods for details.

b , The cross-omics network shown in Fig. c , The number of correlations between faecal carbohydrates and other omics elements shown in Fig. The proportion to all possible correlations is shown.

d , Representative causal mediation models analysing the effects of IL and adiponectin mediating in silico relationships between faecal carbohydrates and HOMA-IR. Causal mediation analysis with multiple test corrections were used to test significance.

Estimates β and P adj values of average causal mediation effects ACME , which are the indirect effects between the metabolites and host markers mediated by cytokines, and average direct effects ADE , which are the direct effects controlling for cytokines, are described.

Age and sex were adjusted in the models. The detailed information is reported in Supplementary Table a , b , PCA plots of metabolites in cell-free supernatants of 22 bacterial strains listed in a.

These strains were selected based on the findings from the genus-level co-occurrence Fig. The strains from genera and species relating to IR-related markers shown in Extended Data Fig. The top 10 metabolites contributing to the PCA separation left panel and 13 out of 15 IR-related carbohydrates identified in Fig.

c , d , The levels of carbohydrate fermentation products c and carbohydrates relating to IR in the human cohort d in the cell-free supernatants. e , Pie charts summarizing the consumption and production of carbohydrates shown in d. Those significantly decreased or increased compared with the vehicle control group were considered as consumption or production.

f , The top consumers of carbohydrates, which summarizes the results shown in e. Representative data of two independent experiments.

c , d , Data are mean and s. a , Body mass change from the baseline. indistinctus AI groups, respectively. Pooled data of three independent experiments. Pooled data of two independent experiments.

k , l , Representative images of phosphorylated Akt p-Akt at S and total Akt in the liver and epidydimal fat eWAT in mice administered Alistipes indistinctus AI , Alistipes finegoldii AF , and PBS as vehicle control k. The raw images of blotting membranes are shown in Supplementary Fig.

P values for interactions between time and group are described in m. Other metabolic measures are reported in Supplementary Table Representative data of two independent experiments c—g , k—o. a , Density plots indicate median and distribution.

a , PCA plots of metabolites in caecal contents of AI-administered mice. The top 10 metabolites contributing to the PCA separation left panel and 12 out of 15 IR-related carbohydrates identified in Fig.

b , The PC1 of PCA plots in Fig. The detailed statistics of all caecal metabolites are reported in Supplementary Table e , A schematic summary. In this study, we combined faecal metabolome, 16S rRNA gene sequencing, and metagenome data with host metabolome, transcriptome, and cytokine data to comprehensively delineate the involvement of gut microbiota in IR upper panel.

Carbohydrate degradation products such as monosaccharides are prominently increased in IR middle panel. Metagenomic findings show that the degradation and utilization of poly- and disaccharides are facilitated in IR and that these microbial functions are strongly associated with faecal monosaccharides.

Further analysis also suggests that the effects of these metabolites on host metabolic parameters such as BMI are in part mediated by specific cytokines. Finally, our animal experiments provide evidence showing that oral administration of AI, a candidate strain selected based on human cohort findings, reduces intestinal carbohydrates and lipid accumulation, thereby leading to the amelioration of IR lower panel.

Taken together, our study provides novel insights into the mechanisms of host-microbe interplays in IR. b , Box plots indicate the median, upper and lower quartiles, and upper and lower extremes except for outliers.

Two-sided Wilcoxon rank-sum test b—d. Raw images of blotting membranes. a,b, The blotting membranes images of p-AKT and total AKT in the liver a and epidydimal fat b. Molecular mass kDa is shown on the left. Relating to Extended Data Fig. Open Access This article is licensed under a Creative Commons Attribution 4.

Reprints and permissions. Gut microbial carbohydrate metabolism contributes to insulin resistance. Download citation. Received : 25 March Accepted : 20 July Published : 30 August Issue Date : 14 September Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

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Abstract Insulin resistance is the primary pathophysiology underlying metabolic syndrome and type 2 diabetes 1 , 2. Full size image. Faecal carbohydrates are increased in IR We next searched for the associations between clinical phenotypes and faecal metabolite CAGs Fig.

Microorganism—metabolite relationships in IR We next investigated the alteration in gut microbiota and the functions of gut microbiota that are associated with IR. Faecal carbohydrates and inflammation in IR Consistent with previous reports 1 , 2 , the host cytokine, metabolomic and transcriptomic signatures were highly associated with IR Supplementary Tables 19 — IS-associated bacteria in experimental models The above findings from human multi-omics analyses revealed an association between carbohydrate metabolites and IR pathology.

Discussion To deepen our understanding of the host—microorganism relationship in IR, we used multimodal techniques to conduct a comprehensive and extensive study investigating the interactions between the gut microbiome and metabolic diseases in humans.

Methods Study participants and data collection The study participants were recruited from to during their annual health check-ups at the University of Tokyo Hospital. Lipidomics of faecal and plasma samples The lipidomics analysis was performed according to a previously reported study Reanalysis of publicly available metabolomic data To validate the associations between clinical markers and faecal metabolites, we used the metabolomic data of TwinsUK 17 and HMP2 ref.

DNA extraction from faecal samples DNA extraction was performed according to a protocol described previously 47 with slight modifications.

Comparison of KEGG organism genomes The list of KEGG organisms used for this genome analysis is listed in Supplementary Table RNA extraction from PBMC Blood samples were collected in Vacutainer CPT tubes Becton Dickinson and mixed with the anticoagulant by gently inverting the tubes 8 to 10 times.

CAGE analysis The CAGE libraries were constructed according to the dual-index nanoCAGE protocol, a template-switching-based variation of the standard CAGE protocol designed for low quantities of RNA 55 , Metabolite measurement in bacterial culture The following strains were used for this culture analysis: A.

Western blot analysis of phosphorylated AKT To analyse phosphorylation of AKT p-AKT at Ser, the mice administered with A. Hyperinsulinaemic—euglycaemic clamp test The protocol has been published elsewhere 62 , Analysis of triglyceride contents in the liver For the necropsy, the mice were anesthetized using isoflurane MSD , and the left half of liver was dissected, weighed and frozen in liquid nitrogen.

ROC curve analysis of omics datasets To analyse ROC curves of omics datasets, the datasets of faecal metabolomics, including hydrophilic and lipid metabolites, faecal 16S rRNA gene sequencing at the genus level, faecal metagenome consisting of KEGG orthologues and clinical metadata, were included.

Construction of cross-omics networks To construct and visualize a correlation-based network of omics data, we first analysed IR-associated host signatures using plasma cytokines, plasma metabolites and CAGE promoter expression data.

Explained variance of plasma cytokines by omics data To assess the explained variance of ten plasma cytokines, we established random-forest models using the R package caret v. Causal mediation analysis To infer the effects of plasma cytokines on in silico causal relationships between faecal carbohydrates and IR markers HOMA-IR, BMI, triglycerides and HDL-C , we performed causal mediation analysis using the R package mediation v.

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