Supplemental Material for Infant Fecal Microbiota Composition and Attention to Emotional Faces

Abstract Background Autism spectrum disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis, changes in microbiota composition as well as in the fecal, serum, and urine levels of microbial metabolites. Yet a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolite p-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice. Results Mice exposed to p-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced by p-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further, p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred from p-Cresol-treated mice to control mice by fecal microbiota transplantation (FMT). We also showed that mice transplanted with the microbiota of p-Cresol-treated mice exhibited increased fecal p-Cresol excretion, compared to mice transplanted with the microbiota of control mice. In addition, we identified possible p-Cresol bacterial producers. Lastly, the microbiota of control mice rescued social interactions, dopamine neurons excitability, and fecal p-Cresol levels when transplanted to p-Cresol-treated mice. Conclusions The microbial metabolite p-Cresol induces selectively ASD core behavioral symptoms in mice. Social behavior deficits induced by p-Cresol are dependant on changes in microbiota composition. Our study paves the way for therapeutic interventions targeting the microbiota and p-Cresol production to treat patients with ASD.

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Efficacy of metformin and fermentable fiber combination therapy in adolescents with severe obesity and insulin resistance: study protocol for a double-blind randomized controlled trial

Trials ◽

10.1186/s13063-021-05060-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Edward C. Deehan ◽

Eloisa Colin-Ramirez ◽

Lucila Triador ◽

Karen L. Madsen ◽

Carla M. Prado ◽

...

Keyword(s):

Insulin Resistance ◽

Randomized Controlled Trial ◽

Combination Therapy ◽

Gut Microbiome ◽

Controlled Trial ◽

Fecal Microbiota ◽

Metabolic Effects ◽

Microbiota Composition ◽

Randomized Controlled ◽

Secondary Outcomes

Abstract Background Accumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal models have established that the addition of fiber to metformin monotherapy improves glucose tolerance. However, possible synergistic effects of combination therapy (metformin plus fiber) have not been investigated in humans. Moreover, the underlying mechanisms of synergy have yet to be elucidated. The aim of this study is to compare in adolescents with obesity the metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone. We will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome. Methods This is a parallel three-armed, double-blinded, randomized controlled trial. Adolescents (aged 12–18 years) with obesity, insulin resistance (IR), and a family history of type 2 diabetes mellitus (T2DM) will receive either metformin (850 mg p.o. twice/day), fermentable fibers (35 g/day), or a combination of metformin plus fiber for 12 months. Participants will be seen at baseline, 3, 6, and 12 months, with a phone follow-up at 1 and 9 months. Primary and secondary outcomes will be assessed at baseline, 6, and 12 months. The primary outcome is change in IR estimated by homeostatic model assessment of IR; key secondary outcomes include changes in the Matsuda index, oral disposition index, body mass index z-score, and fat mass to fat-free mass ratio. To gain mechanistic insight, endpoints that reflect host-microbiota interactions will also be assessed: obesity-related immune, metabolic, and satiety markers; humoral metabolites; and fecal microbiota composition, short-chain fatty acids, and bile acids. Discussion This study will compare the potential metabolic benefits of fiber with those of metformin in adolescents with obesity, determine if metformin and fiber act synergistically to improve IR, and elucidate whether the metabolic benefits of metformin and fiber associate with changes in fecal microbiota composition and the output of health-related metabolites. This study will provide insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for T2DM prevention. Trial registration ClinicalTrials.gov NCT04578652. Registered on 8 October 2020.

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Fecal microbiota transplantation alleviates myocardial damage in myocarditis by restoring the microbiota composition

Pharmacological Research ◽

10.1016/j.phrs.2018.11.042 ◽

2019 ◽

Vol 139 ◽

pp. 412-421 ◽

Cited By ~ 12

Author(s):

Xiao-Fan Hu ◽

Wen-Yong Zhang ◽

Qiang Wen ◽

Wei-Jun Chen ◽

Zhi-Min Wang ◽

...

Keyword(s):

Fecal Microbiota Transplantation ◽

Myocardial Damage ◽

Fecal Microbiota ◽

Microbiota Composition

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In vitro fermentation of six kinds of edible mushrooms and its effects on fecal microbiota composition

LWT ◽

10.1016/j.lwt.2018.06.012 ◽

2018 ◽

Vol 96 ◽

pp. 627-635 ◽

Cited By ~ 9

Author(s):

Ruiqiu Zhao ◽

Wenjian Yang ◽

Fei Pei ◽

Liyan Zhao ◽

Qiuhui Hu

Keyword(s):

Fecal Microbiota ◽

Edible Mushrooms ◽

Microbiota Composition ◽

In Vitro Fermentation

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Effects of Dietary Supplementation With Enterococcus faecium and Clostridium butyricum, Either Alone or in Combination, on Growth and Fecal Microbiota Composition of Post-weaning Pigs at a Commercial Farm

Frontiers in Veterinary Science ◽

10.3389/fvets.2019.00026 ◽

2019 ◽

Vol 6 ◽

Cited By ~ 5

Author(s):

Yoshiaki Sato ◽

Yasutoshi Kuroki ◽

Kentaro Oka ◽

Motomichi Takahashi ◽

Shengbin Rao ◽

...

Keyword(s):

Enterococcus Faecium ◽

Dietary Supplementation ◽

Fecal Microbiota ◽

Clostridium Butyricum ◽

Microbiota Composition ◽

Commercial Farm ◽

Weaning Pigs

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Fecal microbiota transplantation from high caloric-fed donors alters glucose metabolism in recipient mice, independently of adiposity or exercise status

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00037.2020 ◽

2020 ◽

Vol 319 (1) ◽

pp. E203-E216

Author(s):

Jereon Zoll ◽

Mark N. Read ◽

Sarah E. Heywood ◽

Emma Estevez ◽

Jessica P. S. Marshall ◽

...

Keyword(s):

Body Composition ◽

Glucose Metabolism ◽

Glucose Intolerance ◽

Fecal Microbiota Transplantation ◽

High Energy ◽

Fecal Microbiota ◽

Metabolic Effects ◽

Microbiota Composition ◽

No Donor ◽

Glucose Levels

Studies suggest the gut microbiota contributes to the development of obesity and metabolic syndrome. Exercise alters microbiota composition and diversity and is protective of these maladies. We tested whether the protective metabolic effects of exercise are mediated through fecal components through assessment of body composition and metabolism in recipients of fecal microbiota transplantation (FMT) from exercise-trained (ET) mice fed normal or high-energy diets. Donor C57BL/6J mice were fed a chow or high-fat, high-sucrose diet (HFHS) for 4 wk to induce obesity and glucose intolerance. Mice were divided into sedentary (Sed) or ET groups (6 wk treadmill-based ET) while maintaining their diets, resulting in four donor groups: chow sedentary (NC-Sed) or ET (NC-ET) and HFHS sedentary (HFHS-Sed) or ET (HFHS-ET). Chow-fed recipient mice were gavaged with feces from the respective donor groups weekly, creating four groups (NC-Sed-R, NC-ET-R, HFHS-Sed-R, HFHS-ET-R), and body composition and metabolism were assessed. The HFHS diet led to glucose intolerance and obesity in the donors, whereas exercise training (ET) restrained adiposity and improved glucose tolerance. No donor group FMT altered recipient body composition. Despite unaltered adiposity, glucose levels were disrupted when challenged in mice receiving feces from HFHS-fed donors, irrespective of donor-ET status, with a decrease in insulin-stimulated glucose clearance into white adipose tissue and large intestine and specific changes in the recipient’s microbiota composition observed. FMT can transmit HFHS-induced disrupted glucose metabolism to recipient mice independently of any change in adiposity. However, the protective metabolic effect of ET on glucose metabolism is not mediated through fecal factors.

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Effect of dietary fiber content on nutrient digestibility and fecal microbiota composition in growing-finishing pigs

PLoS ONE ◽

10.1371/journal.pone.0206159 ◽

2018 ◽

Vol 13 (10) ◽

pp. e0206159 ◽

Cited By ~ 14

Author(s):

Mathilde Le Sciellour ◽

Etienne Labussière ◽

Olivier Zemb ◽

David Renaudeau

Keyword(s):

Dietary Fiber ◽

Fecal Microbiota ◽

Nutrient Digestibility ◽

Fiber Content ◽

Finishing Pigs ◽

Microbiota Composition

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Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition

Cells ◽

10.3390/cells8060517 ◽

2019 ◽

Vol 8 (6) ◽

pp. 517 ◽

Cited By ~ 12

Author(s):

Claudia Burrello ◽

Maria Rita Giuffrè ◽

Angeli Dominique Macandog ◽

Angelica Diaz-Basabe ◽

Fulvia Milena Cribiù ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiota ◽

Immune Cells ◽

Intestinal Inflammation ◽

Fecal Microbiota Transplantation ◽

Experimental Colitis ◽

Fecal Microbiota ◽

Microbiota Composition ◽

Chronic Intestinal Inflammation ◽

Gut Microbiota Composition

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

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