Summary of Study ST003149

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001958. The data can be accessed directly via it's Project DOI: 10.21228/M8MX5P This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST003149
Study Title	Impact of early-life exposure to a potent aryl hydrocarbon receptor ligand on gut microbiota and host glucose homeostasis in C57BL/6J male mice (Part I)
Study Summary	This study aimed to explore the association between early-life exposure to a potent aryl hydrocarbon receptor (AHR) agonist and persistent disruptions in the microbiota, leading to impaired metabolic homeostasis later in life. This study utilized metagenomics, NMR- and mass spectrometry-based metabolomics, and biochemical assays to analyze the gut microbiome composition and function, as well as the physiological and metabolic effects of early-life exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF) in conventional, germ-free (GF), and Ahr-null mice. The impact of TCDF on Akkermansia muciniphila (A. muciniphila) in vitro was assessed using optical density (OD 600), flow cytometry, transcriptomics, and mass spectrometry-based metabolomics. TCDF-exposed mice exhibited disruption in the gut microbiome community structure and function, characterized by lower abundances of A. muciniphila, lower levels of cecal short chain fatty acids (SCFAs) and indole-3-lactic acid (ILA), and a reduction in gut hormones GLP-1 and PYY. Importantly, microbial and metabolic phenotypes associated with early-life POP exposure were transferable to GF recipients in the absence of POP carry-over. In addition, AHR-independent interactions between POPs and the microbiota were observed, significantly affected the growth, physiology, gene expression, and metabolic activity of A. muciniphila, resulting in suppressed activity along the ILA pathway.
Institute	Pennsylvania State University
Department	Department of Veterinary and Biomedical Sciences
Last Name	Koo
First Name	Imhoi
Address	307B Life Science Building
Email	iuk41@psu.edu
Phone	+1 814-865-7803
Submit Date	2024-03-28
Raw Data Available	Yes
Raw Data File Type(s)	fid
Analysis Type Detail	NMR
Release Date	2024-04-30
Release Version	1

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Project:

Project ID:	PR001958
Project DOI:	doi: 10.21228/M8MX5P
Project Title:	Impact of early-life exposure to a potent aryl hydrocarbon receptor ligand on gut microbiota and host glucose homeostasis in C57BL/6J male mice
Project Summary:	This study aimed to explore the association between early-life exposure to a potent aryl hydrocarbon receptor (AHR) agonist and persistent disruptions in the microbiota, leading to impaired metabolic homeostasis later in life. This study utilized metagenomics, NMR- and mass spectrometry-based metabolomics, and biochemical assays to analyze the gut microbiome composition and function, as well as the physiological and metabolic effects of early-life exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF) in conventional, germ-free (GF), and Ahr-null mice. The impact of TCDF on Akkermansia muciniphila (A. muciniphila) in vitro was assessed using optical density (OD 600), flow cytometry, transcriptomics, and mass spectrometry-based metabolomics. TCDF-exposed mice exhibited disruption in the gut microbiome community structure and function, characterized by lower abundances of A. muciniphila, lower levels of cecal short chain fatty acids (SCFAs) and indole-3-lactic acid (ILA), and a reduction in gut hormones GLP-1 and PYY. Importantly, microbial and metabolic phenotypes associated with early-life POP exposure were transferable to GF recipients in the absence of POP carry-over. In addition, AHR-independent interactions between POPs and the microbiota were observed, significantly affected the growth, physiology, gene expression, and metabolic activity of A. muciniphila, resulting in suppressed activity along the ILA pathway.
Institute:	Pennsylvania State University
Department:	Department of Veterinary and Biomedical Sciences
Last Name:	Koo
First Name:	Imhoi
Address:	307B Life Science Building
Email:	iuk41@psu.edu
Phone:	+1 814-865-7803

Subject:

Subject ID:	SU003266
Subject Type:	Mammal
Subject Species:	Mus musculus
Taxonomy ID:	10090
Age Or Age Range:	4 weeks to 5 months
Gender:	Male

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id	local_sample_id	Sample source	Genotype	Treatment
SA340775	GF.cecal.content_Akkermansia__8	cecal content	GF C57BL/6J mice	ABX water
SA340776	GF.cecal.content_Akkermansia__9	cecal content	GF C57BL/6J mice	ABX water
SA340777	GF.cecal.content_Akkermansia__10	cecal content	GF C57BL/6J mice	ABX water
SA340778	GF.cecal.content_Akkermansia__3	cecal content	GF C57BL/6J mice	Akkermansia
SA340779	GF.cecal.content_Akkermansia__4	cecal content	GF C57BL/6J mice	Akkermansia
SA340780	GF.cecal.content_Akkermansia__5	cecal content	GF C57BL/6J mice	Akkermansia
SA340781	GF.cecal.content_Akkermansia__1	cecal content	GF C57BL/6J mice	Akkermansia
SA340782	GF.cecal.content_Akkermansia__2	cecal content	GF C57BL/6J mice	Akkermansia
SA340783	GF.cecal.content_Akkermansia__11	cecal content	GF C57BL/6J mice	Akkermansia +ABX water
SA340784	GF.cecal.content_Akkermansia__12	cecal content	GF C57BL/6J mice	Akkermansia +ABX water
SA340785	GF.cecal.content_Akkermansia__6	cecal content	GF C57BL/6J mice	Akkermansia +ABX water
SA340786	GF.cecal.content_Akkermansia__7	cecal content	GF C57BL/6J mice	Akkermansia +ABX water
SA340787	GF.cecal.content_cecal.bacteria__9	cecal content	GF C57BL/6J mice	cecal gavage from TCDF group
SA340788	GF.cecal.content_cecal.bacteria__6	cecal content	GF C57BL/6J mice	cecal gavage from TCDF group
SA340789	GF.cecal.content_cecal.bacteria__8	cecal content	GF C57BL/6J mice	cecal gavage from TCDF group
SA340790	GF.cecal.content_cecal.bacteria__7	cecal content	GF C57BL/6J mice	cecal gavage from TCDF group
SA340791	GF.cecal.content_cecal.bacteria__3	cecal content	GF C57BL/6J mice	cecal gavage from vehicle group
SA340792	GF.cecal.content_cecal.bacteria__1	cecal content	GF C57BL/6J mice	cecal gavage from vehicle group
SA340793	GF.cecal.content_cecal.bacteria__4	cecal content	GF C57BL/6J mice	cecal gavage from vehicle group
SA340794	GF.cecal.content_cecal.bacteria__2	cecal content	GF C57BL/6J mice	cecal gavage from vehicle group
SA340795	cecal.content.with.TCDF_long__10	cecal content	WT C57BL/6J mice	TCDF
SA340796	cecal.content.with.TCDF_long__9	cecal content	WT C57BL/6J mice	TCDF
SA340797	cecal.content.with.TCDF_long__11	cecal content	WT C57BL/6J mice	TCDF
SA340798	cecal.content.with.TCDF_long__12	cecal content	WT C57BL/6J mice	TCDF
SA340799	cecal.content.with.TCDF_long__7	cecal content	WT C57BL/6J mice	TCDF
SA340800	cecal.content.with.TCDF_short__12	cecal content	WT C57BL/6J mice	TCDF
SA340801	cecal.content.with.TCDF_short__11	cecal content	WT C57BL/6J mice	TCDF
SA340802	cecal.content.with.TCDF_short__7	cecal content	WT C57BL/6J mice	TCDF
SA340803	cecal.content.with.TCDF_short__8	cecal content	WT C57BL/6J mice	TCDF
SA340804	cecal.content.with.TCDF_short__9	cecal content	WT C57BL/6J mice	TCDF
SA340805	cecal.content.with.TCDF_short__10	cecal content	WT C57BL/6J mice	TCDF
SA340806	cecal.content.with.TCDF_long__8	cecal content	WT C57BL/6J mice	TCDF
SA340807	cecal.content.with.TCDF_long__2	cecal content	WT C57BL/6J mice	vehicle
SA340808	cecal.content.with.TCDF_long__3	cecal content	WT C57BL/6J mice	vehicle
SA340809	cecal.content.with.TCDF_long__4	cecal content	WT C57BL/6J mice	vehicle
SA340810	cecal.content.with.TCDF_long__6	cecal content	WT C57BL/6J mice	vehicle
SA340811	cecal.content.with.TCDF_short__2	cecal content	WT C57BL/6J mice	vehicle
SA340812	cecal.content.with.TCDF_short__5	cecal content	WT C57BL/6J mice	vehicle
SA340813	cecal.content.with.TCDF_short__6	cecal content	WT C57BL/6J mice	vehicle
SA340814	cecal.content.with.TCDF_short__4	cecal content	WT C57BL/6J mice	vehicle
SA340815	cecal.content.with.TCDF_short__3	cecal content	WT C57BL/6J mice	vehicle
SA340816	cecal.content.with.TCDF_long__1	cecal content	WT C57BL/6J mice	vehicle
SA340817	cecal.content.with.TCDF_short__1	cecal content	WT C57BL/6J mice	vehicle
SA340818	cecal.content.with.TCDF_long__5	cecal content	WT C57BL/6J mice	vehicle
SA340819	AHR.KO.liver.lipid.with.TCDF__5	liver	Ahr-/- C57BL/6J mice	TCDF
SA340820	AHR.KO.liver.lipid.with.TCDF__6	liver	Ahr-/- C57BL/6J mice	TCDF
SA340821	AHR.KO.liver.lipid.with.TCDF__8	liver	Ahr-/- C57BL/6J mice	TCDF
SA340822	AHR.KO.liver.lipid.with.TCDF__4	liver	Ahr-/- C57BL/6J mice	TCDF
SA340823	AHR.KO.liver.lipid.with.TCDF__7	liver	Ahr-/- C57BL/6J mice	vehicle
SA340824	AHR.KO.liver.lipid.with.TCDF__3	liver	Ahr-/- C57BL/6J mice	vehicle
SA340825	AHR.KO.liver.lipid.with.TCDF__2	liver	Ahr-/- C57BL/6J mice	vehicle
SA340826	AHR.KO.liver.lipid.with.TCDF__1	liver	Ahr-/- C57BL/6J mice	vehicle
SA340831	GF.liver.lipid._cecal.bacteria__6	liver	GF C57BL/6J mice	cecal gavage from TCDF group
SA340832	GF.liver.lipid._cecal.bacteria__9	liver	GF C57BL/6J mice	cecal gavage from TCDF group
SA340833	GF.liver.lipid._cecal.bacteria__10	liver	GF C57BL/6J mice	cecal gavage from TCDF group
SA340834	GF.liver.lipid._cecal.bacteria__8	liver	GF C57BL/6J mice	cecal gavage from TCDF group
SA340835	GF.liver.lipid._cecal.bacteria__7	liver	GF C57BL/6J mice	cecal gavage from TCDF group
SA340836	GF.liver.lipid._cecal.bacteria__1	liver	GF C57BL/6J mice	cecal gavage from vehicle group
SA340837	GF.liver.lipid._cecal.bacteria__5	liver	GF C57BL/6J mice	cecal gavage from vehicle group
SA340838	GF.liver.lipid._cecal.bacteria__4	liver	GF C57BL/6J mice	cecal gavage from vehicle group
SA340839	GF.liver.lipid._cecal.bacteria__3	liver	GF C57BL/6J mice	cecal gavage from vehicle group
SA340840	GF.liver.lipid._cecal.bacteria__2	liver	GF C57BL/6J mice	cecal gavage from vehicle group
SA340827	GF.liver.lipid.with.TCDF__6	liver	GF C57BL/6J mice	TCDF
SA340828	GF.liver.lipid.with.TCDF__7	liver	GF C57BL/6J mice	TCDF
SA340829	GF.liver.lipid.with.TCDF__5	liver	GF C57BL/6J mice	TCDF
SA340830	GF.liver.lipid.with.TCDF__8	liver	GF C57BL/6J mice	TCDF
SA340841	GF.liver.lipid.with.TCDF__3	liver	GF C57BL/6J mice	vehicle
SA340842	GF.liver.lipid.with.TCDF__2	liver	GF C57BL/6J mice	vehicle
SA340843	GF.liver.lipid.with.TCDF__4	liver	GF C57BL/6J mice	vehicle
SA340844	GF.liver.lipid.with.TCDF__1	liver	GF C57BL/6J mice	vehicle
SA340845	liver.lipid.with.TCDF_short__111	liver	WT C57BL/6J mice	TCDF
SA340846	liver.lipid.with.TCDF_short__110	liver	WT C57BL/6J mice	TCDF
SA340847	liver.lipid.with.TCDF_short__109	liver	WT C57BL/6J mice	TCDF
SA340848	liver.lipid.with.TCDF_short__107	liver	WT C57BL/6J mice	TCDF
SA340849	liver.lipid.with.TCDF_short__108	liver	WT C57BL/6J mice	TCDF
SA340850	liver.lipid.with.TCDF_short__112	liver	WT C57BL/6J mice	TCDF
SA340851	liver.with.TCDF_.long__12	liver	WT C57BL/6J mice	TCDF
SA340852	liver.with.TCDF_.long__7	liver	WT C57BL/6J mice	TCDF
SA340853	liver.with.TCDF_short__7	liver	WT C57BL/6J mice	TCDF
SA340854	liver.with.TCDF_.long__9	liver	WT C57BL/6J mice	TCDF
SA340855	liver.with.TCDF_.long__10	liver	WT C57BL/6J mice	TCDF
SA340856	liver.with.TCDF_.long__11	liver	WT C57BL/6J mice	TCDF
SA340857	liver.with.TCDF_short__12	liver	WT C57BL/6J mice	TCDF
SA340858	liver.lipid.with.TCDF_long__207	liver	WT C57BL/6J mice	TCDF
SA340859	liver.lipid.with.TCDF_long__208	liver	WT C57BL/6J mice	TCDF
SA340860	liver.with.TCDF_short__9	liver	WT C57BL/6J mice	TCDF
SA340861	liver.with.TCDF_short__10	liver	WT C57BL/6J mice	TCDF
SA340862	liver.with.TCDF_.long__8	liver	WT C57BL/6J mice	TCDF
SA340863	liver.with.TCDF_short__11	liver	WT C57BL/6J mice	TCDF
SA340864	liver.lipid.with.TCDF_long__210	liver	WT C57BL/6J mice	TCDF
SA340865	liver.lipid.with.TCDF_long__209	liver	WT C57BL/6J mice	TCDF
SA340866	liver.with.TCDF_short__8	liver	WT C57BL/6J mice	TCDF
SA340867	liver.lipid.with.TCDF_long__212	liver	WT C57BL/6J mice	TCDF
SA340868	liver.lipid.with.TCDF_long__211	liver	WT C57BL/6J mice	TCDF
SA340869	liver.with.TCDF_short__4	liver	WT C57BL/6J mice	vehicle
SA340870	liver.with.TCDF_short__5	liver	WT C57BL/6J mice	vehicle
SA340871	liver.with.TCDF_short__3	liver	WT C57BL/6J mice	vehicle
SA340872	liver.with.TCDF_short__2	liver	WT C57BL/6J mice	vehicle
SA340873	liver.with.TCDF_short__6	liver	WT C57BL/6J mice	vehicle
SA340874	liver.with.TCDF_short__1	liver	WT C57BL/6J mice	vehicle

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Collection:

Collection ID:	CO003259
Collection Summary:	Liver, cecal content, and intestinal tissue samples were collected immediately after sacrifice by carbon dioxide asphyxiation and kept at -80°C. Urine and feces were collected using separate cages before sacrifice and kept at -80°C.
Sample Type:	liver, cecal content, urine

Treatment:

Treatment ID:	TR003275
Treatment Summary:	1. After feed training, mice were fed pills containing TCDF (dissolved in acetone) or acetone alone as vehicle, and one pill uniformly contained 0.46 µg TCDF (24 µg/kg as final dose). Mice were housed singly in an empty cage and monitored to ensure the pill was consumed in the morning for 5 days. 2. TCDF (24 µg/kg) or corn oil as vehicle were administered to age-matched male GF and Ahr-/- mice by oral gavage once daily for five days (n = 4 per group). 3. Four-week-old male GF C57BL/6J mice were orally gavaged with 100 µL of cecal suspension (100 mg in 1 mL sterile BHI CHV media) from vehicle or TCDF treated mice in long-duration model. 4. A. muciniphila was administered to GF mice by oral gavage at one dose 107 CFU/0.1 mL suspended in sterile BHI CHV media containing an end concentration of glycerol (15% vol/vol).

Treatment ID:

TR003275

Treatment Summary:

1. After feed training, mice were fed pills containing TCDF (dissolved in acetone) or acetone alone as vehicle, and one pill uniformly contained 0.46 µg TCDF (24 µg/kg as final dose). Mice were housed singly in an empty cage and monitored to ensure the pill was consumed in the morning for 5 days. 2. TCDF (24 µg/kg) or corn oil as vehicle were administered to age-matched male GF and Ahr-/- mice by oral gavage once daily for five days (n = 4 per group). 3. Four-week-old male GF C57BL/6J mice were orally gavaged with 100 µL of cecal suspension (100 mg in 1 mL sterile BHI CHV media) from vehicle or TCDF treated mice in long-duration model. 4. A. muciniphila was administered to GF mice by oral gavage at one dose 107 CFU/0.1 mL suspended in sterile BHI CHV media containing an end concentration of glycerol (15% vol/vol).

Sample Preparation:

Sampleprep ID:	SP003273
Sampleprep Summary:	For preparation of urine samples, 550 μL urine was blended with 55 μL of phosphate buffer (K2HPO4/NaH2PO4, 1.5 M, pH 7.4, 100% D2O) containing 0.01% TSP for chemical shift reference (δ0.00). After centrifugation (11 180 ×g, 4 °C) for 10 min, 550 μL supernatant was transferred into 5 mm NMR tubes for NMR analysis. Each liver tissue sample (55 ± 5 mg) was extracted three times with 600 μL of methanol/H2O (2:1) using a Qiagen tissue-lyzer. Three resultant supernatants were combined and subjected to centrifugation (16 099 ×g, 4 °C, 10 min). After removing methanol in vacuo, the resultant supernatant was lyophilized, weighed, and reconstituted into 600 μL phosphate buffer (0.1 M, K2HPO4/NaH2PO4, pH 7.4) containing 0.005% TSP, 50% D2O and 0.01% NaN3. After final centrifugation (16 099 ×g, 4 °C, 10 min), each supernatant (550 μL) was transferred into a 5 mm NMR tube for NMR analysis. Each fecal sample (55 ± 5 mg) were extracted twice with 500 μL phosphate buffer (0.1 M, K2HPO4/NaH2PO4, pH 7.4) containing 0.005% TSP, 30% D2O and 0.01% NaN3. After centrifugation (16 099 ×g, 4 °C, 10 min), 600 μL combined supernatants were transferred into 5 mm NMR tubes for NMR analysis. For liver lipid quantification, 50 mg of liver tissue was homogenized in 1 mL pre-cooled chloroform/methanol mix [1:1 (v/v)], followed by adding 296 µL water. After centrifugation (10,000 g, 4°C) for 10 min, the lower phase was dried in a vacuum and reconstituted in 600 µL of deuterated chloroform containing 0.03% (v/v) tetramethylsilane (TMS).

Sampleprep ID:

SP003273

Sampleprep Summary:

For preparation of urine samples, 550 μL urine was blended with 55 μL of phosphate buffer (K2HPO4/NaH2PO4, 1.5 M, pH 7.4, 100% D2O) containing 0.01% TSP for chemical shift reference (δ0.00). After centrifugation (11 180 ×g, 4 °C) for 10 min, 550 μL supernatant was transferred into 5 mm NMR tubes for NMR analysis. Each liver tissue sample (55 ± 5 mg) was extracted three times with 600 μL of methanol/H2O (2:1) using a Qiagen tissue-lyzer. Three resultant supernatants were combined and subjected to centrifugation (16 099 ×g, 4 °C, 10 min). After removing methanol in vacuo, the resultant supernatant was lyophilized, weighed, and reconstituted into 600 μL phosphate buffer (0.1 M, K2HPO4/NaH2PO4, pH 7.4) containing 0.005% TSP, 50% D2O and 0.01% NaN3. After final centrifugation (16 099 ×g, 4 °C, 10 min), each supernatant (550 μL) was transferred into a 5 mm NMR tube for NMR analysis. Each fecal sample (55 ± 5 mg) were extracted twice with 500 μL phosphate buffer (0.1 M, K2HPO4/NaH2PO4, pH 7.4) containing 0.005% TSP, 30% D2O and 0.01% NaN3. After centrifugation (16 099 ×g, 4 °C, 10 min), 600 μL combined supernatants were transferred into 5 mm NMR tubes for NMR analysis. For liver lipid quantification, 50 mg of liver tissue was homogenized in 1 mL pre-cooled chloroform/methanol mix [1:1 (v/v)], followed by adding 296 µL water. After centrifugation (10,000 g, 4°C) for 10 min, the lower phase was dried in a vacuum and reconstituted in 600 µL of deuterated chloroform containing 0.03% (v/v) tetramethylsilane (TMS).

Analysis:

Analysis ID:	AN005167
Analysis Type:	NMR
Analysis Protocol File:	PSU_Protocol_for_NMR_metabolomics.pdf
Num Factors:	17
Num Metabolites:	20
Units:	µmol/g

NMR:

NMR ID:	NM000278
Analysis ID:	AN005167
Instrument Name:	Bruker Avance NEO 600 MHz
Instrument Type:	FT-NMR
NMR Experiment Type:	1D-1H
Spectrometer Frequency:	600 MHz