Parabacteroides distasonis Alleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids

Wang, Kai; Liao, Min; Zhou, Nan; Li, Bao; Ma, Ke; Zheng, Zhongyong; Wang, Yujing; Liu, Chang; Wang, Wenzhao; Wang, Jun; Liu, Shuang‐Jiang; Liu, Hongwei

doi:10.1016/j.celrep.2018.12.028

Cited by 758 publications

(637 citation statements)

References 73 publications

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“…On the other hand, in the diseased state (UC), other taxa including R. torques, B. massiliensis, P. distasonis, and D. invisus are more impactful. Again, the published literature supports the above claims [29,26,55,33]. Thus our methods allow us to identify potentially beneficial and pathogenic bacteria in microbiomes.…”

Section: Results and Analysissupporting

confidence: 75%

Causal Inference in Microbiomes Using Intervention Calculus

Sazal

Stebliankin

Mathee

et al. 2020

Preprint

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Inferring causal effects is critically important in biomedical research as it allows us to move from the typical paradigm of associational studies to causal inference, and can impact treatments and therapeutics. Association patterns can be coincidental and may lead to wrong inferences in complex systems. Microbiomes are highly complex, diverse, and dynamic environments. Microbes are key players in health and diseases. Hence knowledge of genuine causal relationships among the entities in a microbiome, and the impact of internal and external factors on microbial abundance and interactions are essential for understanding disease mechanisms and making treatment recommendations.In this paper, we investigate fundamental causal inference techniques to measure the causal effects of various entities in a microbiome. In particular, we show how to use these techniques on microbiome datasets to study the rise and impact of antibiotic-resistance in microbiomes. Our main contributions include the following. We introduce a novel pipeline for microbiome studies, new ideas for experimental design under weaker assumptions, and data augmentation by context embedding. Our pipeline is robust, different from traditional approaches, and able to predict interventional effects without any controlled experiments. Our work shows the advantages of causal inference in identifying potential pathogenic, beneficial, and antibiotic-resistant bacteria. We validate our results using results that were previously published.

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Section: Results and Analysissupporting

confidence: 75%

Causal Inference in Microbiomes Using Intervention Calculus

Sazal

Stebliankin

Mathee

et al. 2020

Preprint

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“…casein versus whole-cell bacterial lysates) would affect gut microbiota community structures, we analyzed freshly collected fecal samples before and throughout the dietary intervention. LFD and WD REF fed mice showed distinct gut microbiota profiles after 12 weeks of feeding (intervention baseline, week 12+0; Figure 1B,C), including ∼10-fold lower abundance of the health-promoting genera, Parasutterella 27 and Parabacteroides 28 , countered by an equally increased abundance of the obesity associated genus Desulfivobrio 30, 31 (Figure 1D) as well as a ∼4-fold increase in the Firmicutes to Bacteroidetes (F/B) ratio (Figure 1E). Interestingly, WD CNTL fed mice showed negligible changes in the microbiome signature during the 6 weeks of intervention (Figure 1B-F & S1A-B), suggesting that the added lipid source had limited influence on the intestinal ecology.…”

Section: Resultsmentioning

confidence: 99%

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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“…Parabacteroides abundance also increased in patients with recurrent CDIs (63). Parabacteroides produces succinate (64), which has been found to promote C. difficile growth following antibiotic treatments (65). Thus, the survival of Parabacteroides after antibiotic treatments could favor the proliferation of C. difficile in infected mice.…”

Section: Effect Of a High-fat/low-protein Keto-like Diet On Antibiotimentioning

confidence: 99%

A High-Fat/High-Protein, Atkins-Type Diet Exacerbates Clostridioides ( Clostridium ) difficile Infection in Mice, whereas a High-Carbohydrate Diet Protects

et al. 2020

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Clostridioides difficile (formerly Clostridium difficile) infection (CDI) can result from the disruption of the resident gut microbiota. Western diets and popular weight-loss diets drive large changes in the gut microbiome; however, the literature is conflicted with regard to the effect of diet on CDI. Using the hypervirulent strain C. difficile R20291 (RT027) in a mouse model of antibiotic-induced CDI, we assessed disease outcome and microbial community dynamics in mice fed two high-fat diets in comparison with a high-carbohydrate diet and a standard rodent diet. The two high-fat diets exacerbated CDI, with a high-fat/high-protein, Atkins-like diet leading to severe CDI and 100% mortality and a high-fat/low-protein, medium-chain-triglyceride (MCT)-like diet inducing highly variable CDI outcomes. In contrast, mice fed a high-carbohydrate diet were protected from CDI, despite the high levels of refined carbohydrate and low levels of fiber in the diet. A total of 28 members of the Lachnospiraceae and Ruminococcaceae decreased in abundance due to diet and/or antibiotic treatment; these organisms may compete with C. difficile for amino acids and protect healthy animals from CDI in the absence of antibiotics. Together, these data suggest that antibiotic treatment might lead to loss of C. difficile competitors and create a favorable environment for C. difficile proliferation and virulence with effects that are intensified by high-fat/high-protein diets; in contrast, high-carbohydrate diets might be protective regardless of the source of carbohydrate or of antibiotic-driven loss of C. difficile competitors. IMPORTANCE The role of Western and weight-loss diets with extreme macronutrient composition in the risk and progression of CDI is poorly understood. In a longitudinal study, we showed that a high-fat/high-protein, Atkins-type diet greatly exacerbated antibiotic-induced CDI, whereas a high-carbohydrate diet protected, despite the high monosaccharide and starch content. Our study results, therefore, suggest that popular high-fat/high-protein weight-loss diets may enhance CDI risk during antibiotic treatment, possibly due to the synergistic effects of a loss of the microorganisms that normally inhibit C. difficile overgrowth and an abundance of amino acids that promote C. difficile overgrowth. In contrast, a high-carbohydrate diet might be protective, despite reports on the recent evolution of enhanced carbohydrate metabolism in C. difficile.

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Parabacteroides distasonis Alleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids

Cited by 758 publications

References 73 publications

Causal Inference in Microbiomes Using Intervention Calculus

Causal Inference in Microbiomes Using Intervention Calculus

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

A High-Fat/High-Protein, Atkins-Type Diet Exacerbates Clostridioides ( Clostridium ) difficile Infection in Mice, whereas a High-Carbohydrate Diet Protects

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Parabacteroides distasonis Alleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids

Cited by 758 publications

References 73 publications

Causal Inference in Microbiomes Using Intervention Calculus

Causal Inference in Microbiomes Using Intervention Calculus

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

A High-Fat/High-Protein, Atkins-Type Diet Exacerbates Clostridioides ( Clostridium ) difficile Infection in Mice, whereas a High-Carbohydrate Diet Protects

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