The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice

Kindt, Alida; Liebisch, Gerhard; Clavel, Thomas; Haller, Dirk; Hörmannsperger, Gabriele; Yoon, Hongsup; Kolmeder, Daniela; Sigrüener, Alexander; Krautbauer, Sabrina; Seeliger, Claudine; Ganzha, Alexandra; Schweizer, Sabine; Morisset, Rosalie; Strowig, Till; Daniel, Hannelore; Helm, Dominic; Küster, Bernhard; Krumsiek, Jan; Ecker, Josef

doi:10.1038/s41467-018-05767-4

Cited by 221 publications

(188 citation statements)

References 77 publications

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“…We additionally observed augmented adiponectin secretion (Figure 4I), pointing towards improved insulin sensitivity in the WD McB group, further supported by the assessment of insulin tolerance and hepatic gene transcription activity of key metabolic enzymes (Figure 4J-K). Of interest, we observed a >10-fold downregulation of Scd1 in the liver of WD McB -fed mice, the hepatic expression of which is a) regulated by the microbiota 40 and b) instrumental in de novo lipogenesis at the onset of metabolic syndrome 41 .…”

Section: Resultsmentioning

confidence: 85%

Lysates ofMethylococcus capsulatusBath induce a lean-like microbiota, intestinal FoxP3⁺RORγt⁺IL-17⁺Tregs and improve metabolism

Jensen

Holm

Larsen

et al. 2019

Preprint

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58Interactions between host and gut microbial communities may be modulated by diets and play 59 pivotal roles in securing immunological homeostasis and health. Here we show that intake of feed 60 based on whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath 61 (McB) as protein source reversed high fat high sucrose-induced changes in the gut microbiota to a 62 state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22°C) and at 63 thermoneutrality (T30°C). McB feeding selectively upregulated triple positive (Foxp3 + RORγt + IL-64 17 + ) regulatory T cells in the small intestine and colon, and enhanced mucus production and 65 glycosylation status suggesting improved gut health. Mice receiving McB lysates further exhibited 66 improved glucose regulation, reduced body and liver fat along with diminished hepatic immune 67 infiltration. Collectively, these data points towards profound whole-body effects elicited by the 68McB lysate suggesting that it may serve as a potent modulator of immunometabolic homeostasis. 69 70 Introduction: 71 72Gut microbes shape intestinal immunity 1 and increase the bioavailability of otherwise indigestible 73 nutrients 2 . A well-balanced community structure is therefore essential for immunometabolic 74 homeostasis, whereas aberrant gut microbiota compositions associate with numerous diseases, both 75 within and outside the gastrointestinal tract 3 . 76While therapeutic implications of rebalancing a mistuned gut microbiota appear promising, 77 inconsistent response rates in relation to both probiotics and fecal transfer studies, with occasional 78 adverse events, emphasize the complexity of such approaches. One example relates to the otherwise 79 promising probiotic candidate Akkermansia muciniphila 4 , where negative effects have been seen in 80 immunocompromised recipients 5,6 . Similarly, Prevotella copri aids in metabolizing fibers in healthy 81 individuals 7 and protects against bacterial invasion in high fiber, chow-fed mice 8 , yet associates 82 with insulin resistance in prediabetic obese individuals and precipitates glucoregulatory 83 impairments in diet-induced obese (DIO) mice 9 . 84 85 An alternative to administering viable microbes is to utilize whole cell lysates, or selected cell 86 components, of non-living bacteria. Apart from alleviating global energy demands, if used as a 87 nutrient source, such components may also potently affect host physiology as recently reported for 88A. muciniphila 10 and Bifidobacterium bifidum 11 . In the latter example, cell surface polysaccharides 89 of B. bifidum were used to induce peripheral immune-tolerance via generation of regulatory T cells 90 (Tregs). The authors reported a pronounced increase in Foxp3 + RORγt + Tregs (pTregs), specifically in 91 lamina propria (LP) of the large intestine (LI) 11 . This cell type is believed to be induced by 92 commensal microbes and has emerged as a potent Treg subset, exhibiting increased lineage stability 93 and enhanced immunosuppressive cap...

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Section: Resultsmentioning

confidence: 85%

Lysates ofMethylococcus capsulatusBath induce a lean-like microbiota, intestinal FoxP3⁺RORγt⁺IL-17⁺Tregs and improve metabolism

Jensen

Holm

Larsen

et al. 2019

Preprint

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“…Several studies support the role of gut microbes as potent regulators of hepatic lipid metabolism. Indeed, comparison of hepatic fatty acid metabolism between germ-free and conventionally raised specific-pathogen-free mice has shown that gut microbes impact the MUFA content and PUFA elongation by modifying Scd1 and Elovl5 expression, respectively (Kindt et al, 2018). In addition, alteration of the expression level of genes involved in hepatic lipid metabolism (Srebp1c, Acc, Fas, Scd1, Acat2, Dgat1, Dgat2, Hmgcs, and Hmgcr) has been reported in TLR5-deficient mice (Singh et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The microbiota regulates lipid metabolization and absorption at the level of the intestinal mucosa (Martinez-Guryn et al, 2018). In addition to that, gut microbes can modify hepatic de novo lipogenesis by modulating expression of genes involved in lipid metabolism and by generating short chain fatty acids (SCFA) that are substrates for hepatic lipogenesis (Singh et al, 2015;Kindt et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Age-Related Changes in the Gut Microbiota Modify Brain Lipid Composition

Albouery

Buteau

Grégoire

et al. 2020

Front. Cell. Infect. Microbiol.

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Understanding the molecular mechanisms underlying the changes observed during aging is a prerequisite to design strategies to prevent age-related diseases. Aging is associated with metabolic changes, including alteration in the brain lipid metabolism. These alterations may contribute to the development of pathophysiological conditions. Modifications in the gut microbiota composition are also observed during aging. As communication axes exist between the gut microbiota and the brain and knowing that microbiota influences the host metabolism, we speculated on whether age-associated modifications in the gut microbiota could be involved in the lipid changes observed in aging brain. For that purpose, germ-free mice were colonized by the fecal microbiota of young or old donor mice. Lipid classes and fatty acid profiles were determined in the brain (cortex), plasma and liver by thin-layer chromatography on silica gel-coated quartz rods and gas chromatography. Gut colonization by microbiota of old mice resulted in a significant increase in total monounsaturated fatty acids (MUFA) and a significant decrease in the relative amounts of cholesterol and total polyunsaturated fatty acids (PUFA) in the cortex. Among the eight most represented fatty acids in the cortex, the relative abundances of five (C18:1n-9, C22:6n-3, C20:4n-6, C18:1n-7, and C20:1n-9) were significantly altered in mice inoculated with an aged microbiota. Liquid chromatography analyses revealed that the relative abundance of major species among phosphatidyl and plasmenylcholine (PC 16:0/18:1), phosphatidyl and plasmenylethanolamine (PE 18:0/22:6), lysophosphatidylethanolamine (LPE 22:6) and sphingomyelins (SM d18:1/18:0) were significantly altered in the cortex of mice colonized by the microbiota obtained from aged donors. Transplantation of microbiota from old mice also modified the lipid class and fatty acid content in the liver. Finally, we found that the expression of several genes involved in MUFA and PUFA synthesis (Scd1, Fads1, Fads2, Elovl2, and Elovl5) was dysregulated in mice inoculated with an Albouery et al.Microbiota Modulates Brain Lipid Composition aged microbiota. In conclusion, our data suggest that changes in gut microbiota that are associated with aging can impact brain and liver lipid metabolisms. Lipid changes induced by an aged microbiota recapitulate some features of aging, thus pointing out the potential role of microbiota alterations in the age-related degradation of the health status.

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“…Finally, the correlations between the milk microbiota and its content in FA and Ig were analyzed. Dietary FA can impact the intestinal microbiota composition [63], and vice versa, the metabolites produced by the microbiota can have an impact on lipid metabolism [64]. Recent studies found associations between the FA profile and the microbiota composition in human milk [33,52].…”

Section: Discussionmentioning

confidence: 99%

Associations of Breast Milk Microbiota, Immune Factors, and Fatty Acids in the Rat Mother–Offspring Pair

et al. 2020

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The present study aimed to analyze the rat breast milk profile of fatty acids (FA), immunoglobulins (Ig), microbiota, and their relationship, and to further assess their associations in the mother–offspring pair. Dams were monitored during the three weeks of gestation, allowed to deliver at term, and followed during two weeks of lactation. At the end of the study, milk was obtained from the dams for the analysis of fatty acids, microbiota composition, immunoglobulins, and cytokines. Moreover, the cecal content and plasma were obtained from both the dams and pups to study the cecal microbiota composition and the plasmatic levels of fatty acids, immunoglobulins, and cytokines. Rat breast milk lipid composition was ~65% saturated FA, ~15% monounsaturated FA, and ~20% polyunsaturated FA. Moreover, the proportions of IgM, IgG, and IgA were ~2%, ~88%, and ~10%, respectively. Breast milk was dominated by members of Proteobacteria, Firmicutes, and Bacteroidetes phyla. In addition, forty genera were shared between the milk and cecal content of dams and pups. The correlations performed between variables showed, for example, that all IgGs subtypes correlated between the three compartments, evidencing their association in the mother-milk-pup line. We established the profile of FA, Ig, and the microbiota composition of rat breast milk. Several correlations in these variables evidenced their association through the mother-milk-pup line. Therefore, it would be interesting to perform dietary interventions during pregnancy and/or lactation that influence the quality of breast milk and have an impact on the offspring.

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The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice

Cited by 221 publications

References 77 publications

Lysates ofMethylococcus capsulatusBath induce a lean-like microbiota, intestinal FoxP3⁺RORγt⁺IL-17⁺Tregs and improve metabolism

Lysates ofMethylococcus capsulatusBath induce a lean-like microbiota, intestinal FoxP3⁺RORγt⁺IL-17⁺Tregs and improve metabolism

Age-Related Changes in the Gut Microbiota Modify Brain Lipid Composition

Associations of Breast Milk Microbiota, Immune Factors, and Fatty Acids in the Rat Mother–Offspring Pair

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The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice

Cited by 221 publications

References 77 publications

Lysates ofMethylococcus capsulatusBath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+Tregs and improve metabolism

Lysates ofMethylococcus capsulatusBath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+Tregs and improve metabolism

Age-Related Changes in the Gut Microbiota Modify Brain Lipid Composition

Associations of Breast Milk Microbiota, Immune Factors, and Fatty Acids in the Rat Mother–Offspring Pair

Contact Info

Product

Resources

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Lysates ofMethylococcus capsulatusBath induce a lean-like microbiota, intestinal FoxP3⁺RORγt⁺IL-17⁺Tregs and improve metabolism

Lysates ofMethylococcus capsulatusBath induce a lean-like microbiota, intestinal FoxP3⁺RORγt⁺IL-17⁺Tregs and improve metabolism