Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health

Table 1 Murine gut microbiome and host outcomes after exposure to high fat diets

Type of high fat diet and duration	Detection method	Key microbial features1						Observation and proposed mechanism for microbial outcomes	Reported host phenotype	Observation and proposed mechanism for host outcomes	Ref.
		F:B	Firmicutes	Bacteroidetes	Proteobacteria	Actinobacteria	Other
HF/HS2 for 8 wk	Fecal 454 [V4]	↑ F:B	↑ unclassified Lachnospiraceae, unclassified Ruminococcaceae, Turicibacter, Dorea, Roseburia	↓ Barnesiella, unclassified Porphyromonadaceae		↑ Bifidobacterium	↑ Akkermansia	Host genetype influences gut microbiota plasticity in response to diet.	↑ Body fat percent		[33]
			↓ Oscillibacter
HF/HS3 for 8 wk	Cecal full length 16S sequencing, shotgun sequencing and transcriptomics	↑ F:B	↑ Mollicutes/ Erysipelotrichaceae				↓ Microbial diversity	Altered substrate availability ↑ microbes with the capacity to import and degrade sugars found in diet and/or host mucosa.	Weight gain,	Increased energy harvest. Specific microbes facilitate the transfer of calories from the diet to the host in the form of SCFAs.	[24]
							↑ Genes for PTS system		↑ Body fat percent
							↑ SCFAs concentration
HF/HS4 for 12 wk	Colonic tissue 454 [V1-2], qPCR and DGGE [V3-5]	↓ F:B	↑ mucin-degrading Ruminococcus torques	↑ Bacteroides-Prevotella spp	↑ Proteobacteria		↓ 16S rRNA gene copies	Diet type and host genotype ↑ bacteria with the ability to bind to glycosylated proteins and colonise mucosal surfaces.	Leaky gut	Diet-induced microbial changes at gut mucosa may aggravate inflammation in genetically susceptible host.	[34]
HFD5 for 8 wk	Fecal 454 [V4] at baseline, Week 4 and Week 8	Progressive ↑ F:B			Progressive ↓ Proteobacteria		Fecal energy and SCFAs fluctuate overtime, varied patterns in cecum and stool	Dietary factors determine microbial composition. Microbial community may adapt to HFD overtime	Weight gain and ↑ fat mass	Microbes may promote obesity via LPS or SCFA modulation of host gene expression rather than energy harvesting.	[35]
HFD5 for 20 wk	Fecal 454 [V4] and qPCR	↑ F:B	↑ Lactobacillus	↓ Bacteroides					Weight gain, IR, fatty liver, adipose, and systemic inflammation	Antibiotic improves metabolic abnormalities. Gut microbiota modulates inflammatory responses.	[36]
HFD5 for 21 wk	Fecal 454 [V1-2] and shotgun sequencing	↑ F:B	↑ Clostridiaceae	↓ Bacteroidaceae, Prevotellaceae and Rickenellaceae	↑ Desulfovibrionaceae		↑ genes for ABC transporters, two-component system and cell motility↓ metabolic genes	Altered substrate availability ↑ microbes with the capacity to enhance nutrient uptake in an environment of limiting substrates	Weight gain		[37]
HFD6 for 8 to 12 wk	Fecal 454 [V6-8]	↑ F:B	↑ Oscillibacter, Blautia	↓ Barnesiella, Parabacteroides					Weight gain, leaky gut, IR, adipose, gut and liver inflammation	Gut bacteria modulate gut barrier integrity. Leaky gut coupled with aberrant microbiota drive metabolic dysfunction.	[38]
			↓ Lactobacillus
HFD7 for 12 wk	Cecal MiSeq [V4], metaproteome, metabolomics		↓ Ruminococcaceae	↑ Rikenellaceae			↑ proteins for amino acid metabolism and transport and cell motility	Altered substrate availability shifts the composition and/or activity of microbiota, which favours amino acid metabolism	Weight gain, hyperglycemia		[39]
			↑ Erysipelotrichales				No difference in microbial richness
HFD8 for 8 wk	Fecal 454 [V1-3], culture	↑ F:B	↑ Ruminococcaceae	↑ Rikenellaceae	↑ Enterobacteriaceae	↓ Bifidobacterium	↑ LPS		Weight gain, hyperglycemia, adipose, systemic and gut inflammation	Leaky gut and LPS induce pro-inflammatory cascade and accelerate obesity development	[40]
			↓ Clostridiales	↓ Bacteroidaceae			No difference microbial diversity
HFD8 for 12 wk	Fecal 454 [V3] at every 2-4 wk	Progressive ↑ F:B	↑ Lachnospiraceae, Ruminococcaceae, Lactococcus	↑ selected OTUs in Bacteroides, Alistipes	Progressive ↑ Desulfovibrionaceae	↓ Bifidobacterium	↓ microbial diversity	Age-related effects and/or altered substrate availability	Weight gain, ↑ fat mass, IGT	↑ antigen load (LPS) and H2S production may lead to chronic inflammation and leaky gut	[41]
				↓ Barnesiella			↑ LPS binding protein
HFD8 for 25 wk	Fecal 454 [V3], DGGE [V3] and T-RFLP		Lineages in Mollicutes/ Erysipelotrichaceae responded differentially		↑ Desulfovibrionaceae	↓ Bifidobacteriaceae		Altered substrate availability and host genetics have differential impact on gut microbial profile	Weight gain, IGT	↓ gut barrier protecting members, ↑ LPS and H2S production promote leaky gut and trigger inflammation	[42]
HFD8 for more than 35 wk	Cecal 454 [V1-2]	↓ F:B	↑ unclassified Lachnospiraceae, Lactococcus, Unclassified Ruminococcaceae, Roseburia	↑ Bacteroides			↑ Mucispirillum	Leptin may affect microbial composition by modulating mucin production in the intestine	Weight gain, ↑ leptin, adipose inflammation	Association between gut bacteria and body fat may be mediated by adipokines and inflammation	[43]
			↓ Allobaculum				↓ Akkermansia
HFD8 for life, gut microbiota at week 62 is described here	Fecal 454 [V3]		↑ selected OTUs in Allobaculum, Ruminococcaceae, Papillibacter, Lactococcus	↑ selected OTUs in Rikenella, Alistipes	↑ Bilophila		↑ Mucispirillum	Altered substrate availability. Low plant polysaccharides may alter the balance of gut barrier protecting bacteria, butyrate producers and pathobionts	Weight gain, IGT, fatty liver, ↓ liver function,	↑ antigen load (mainly LPS) may contribute to metabolic abnormalities	[44,45]
			↓ selected OTUs in Allobaculum	↓ selected OTUs in Bacteroidiales, Prophyromonadaceae.			↑ LPS binding protein
HFD9 for 4 wk	Cecal FISH		↓ Eubacterium rectale/ Closiridium coccoides	↓ Bacteroides-like species		↓ Bifidobacterium	↑ LPS		Weight gain, IR, fatty liver, systemic and adipose inflammation	Dietary fat modulates LPS level in plasma and ↓ gut barrier protecting bacteria, which trigger inflammation and the onset of diabetes and obesity	[4]
HFDs10 with different sources of fat (safflower oil, milk fat or lard) for 24 d	Cecal 454 [V2-4]	↑ F:B in lard HFD			↑ Bilophila in milk fat HFD		↓ microbial diversity in milk fat and safflower oil HFDs	Altered substrate availability. Milk-derived saturated fat ↑ the pool of sulphated bile acid, an antimicrobial but a growth substrate for Bilophila	Gut inflammation in genetically susceptible host	H2S or secondary bile acids from pathobiont may damage gut barrier and drive pro-inflammatory responses	[9]
		↓ F:B in other HFDs
HFDs10 with different sources of fat (safflower oil, milk fat or lard) for 4 wk	Fecal Illumina [V3-4]	↑ F:B in all HFDs			↑ Proteobacteria in milk fat and safflower oil HFDs	↑ Actinobacteria	↑ Tenericutes in lard HFD	Altered substrate availability. Dietary fat source modulates gut microbial profile	Weight gain (highest in milk fat), adipose inflammation (highest in safflower)	Diet induced alterations in the gut microbiota influence localised inflammation	[46]
HFDs11 with different sources of fat (palm, olive or safflower oil) for 8 wk	Fecal MITChip (microarray)	↑ F:B in palm oil HFD only	↑ Bacilli, Clostridium cluster XI, XVII, and XVIII in palm oil HFD only				↓ microbial diversity in palm oil HFD only	Saturated fat diet leads to an overflow of dietary fat in the gut which may have an antimicrobial effect on microbiota	Weight gain (highest in palm oil), IR, fatty liver		[47]

¹This table features the microbial shifts in wild type mice after dietary interventions, patterns for knockout models are excluded. Sampling site and technique used to monitor the hypervariable region of 16S rDNA are noted;

²31.8% and 51.4% calories from fat (corn oil and butter fat) and carbohydrates, respectively, Research Diets, New Brunswick;

³40.6% and 40.7% calories from fat (beef tallow, vegetable shortening) and carbohydrates, respectively, Harlan-Teklad, United States;

⁴60.6% and 26.3% calories from fat (lard) and carbohydrates, respectively, SAFE, France;

⁵45% and 35% calories from fat (lard and soybean oil) and carbohydrates, respectively, Research Diets, New Brunswick;

⁶60% and 20% calories from fat (lard and sunflower oil) and carbohydrates, respectively, in house;

⁷60% and 21% calories from fat (beef tallow and soybean oil) and carbohydrates, respectively, Ssniff GmbH, Germany;

⁸60% and 20% calories from fat (lard and soybean oil) and carbohydrates, respectively, Research Diets, New Brunswick;

⁹72% and < 1% calories from fat (corn oil and lard) and carbohydrates, respectively, SAFE, France;

¹⁰37.5% and 47% calories from fat and carbohydrates, respectively, Harlan-Teklad, United States;

¹¹45% and 35% calories from fat and carbohydrates, respectively, Research Diet Services, The Netherlands. F:B: Firmicutes to Bacteroidetes ratio; HF/HS: High fat and high sugar diet; HFD: High fat diet; PTS: Phosphotransferase system; SCFAs: Short chain fatty acids; ABC transporters: ATP-binding cassette transporters; DGGE: Denaturating gradient gel electrophoresis; T-RFLP: Terminal restriction fragment length polymorphism; IR: Insulin resistance; IGT: Impaired glucose tolerance; LPS: Lipopolysaccharides; OTUs: Operational taxonomic units; H₂S: Hydrogen sulphide; FISH: Fluorescent in situ hybridisation.