Shifts In Intestinal Microbiota Research Articles

Shifts in intestinal microbiota and improvement of sheep immune response to resist Salmonella infection using Toll-like receptor 4 (TLR4) overexpression.

Toll-like receptor 4 (TLR4) identifies Gram-negative bacteria or their products and plays a crucial role in host defense against invading pathogens. In the intestine, TLR4 recognizes bacterial ligands and interacts with the immune system. Although TLR4 signaling is a vital component of the innate immune system, the influence of TLR4 overexpression on innate immune response and its impact on the composition of the intestinal microbiota is unknown. Here, we obtained macrophages from sheep peripheral blood to examine phagocytosis and clearance of Salmonella Typhimurium (S. Typhimurium) in macrophages. Meanwhile, we characterized the complex microbiota inhabiting the stools of TLR4 transgenic (TG) sheep and wild-type (WT) sheep using 16S ribosomal RNA (rRNA) deep sequencing. The results showed that TLR4 overexpression promoted the secretion of more early cytokines by activating downstream signaling pathways after stimulation by S. Typhimurium. Furthermore, diversity analysis demonstrated TLR4 overexpression increased microbial community diversity and regulated the composition of intestinal microbiota. More importantly, TLR4 overexpression adjusted the gut microbiota composition and maintained intestinal health by reducing the ratio of Firmicutes/Bacteroidetes and inflammation and oxidative stress-producing bacteria (Ruminococcaceae, Christensenellaceae) and upregulating the abundance of Bacteroidetes population and short-chain fatty acid (SCFA)-producing bacteria, including Prevotellaceae. These dominant bacterial genera changed by TLR4 overexpression revealed a close correlation with the metabolic pathways of TG sheep. Taken together, our findings suggested that TLR4 overexpression can counteract S. Typhimurium invasion as well as resist intestinal inflammation in sheep by regulating intestinal microbiota composition and enhancing anti-inflammatory metabolites.

Preoperative Microbiomes and Intestinal Barrier Function Can Differentiate Prodromal Alzheimer's Disease From Normal Neurocognition in Elderly Patients Scheduled to Undergo Orthopedic Surgery.

ObjectiveEmerging evidence links perturbations in the microbiome to neurodegeneration in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) and to surgical stress. In this study, we attempted to identify preoperative differences intestinal microbiota (IM) and barrier function between pAD [prodromal AD: Subjective cognitive decline (SCD) and aMCI] patients and normal neurocognition (NC) patients. Additionally, the potential associations between IM and barrier function, inflammation, and the clinical characteristics of pAD were evaluated.DesignEighty elderly patients scheduled to undergo orthopedic surgery were consecutively enrolled and grouped as NC, SCD, and aMCI following neuropsychological assessment. IM was determined by 16S rRNA MiSeq sequencing, and PICRUSt was used to predict functional shifts in IM. Furthermore, we investigated the association between IM and plasma claudin-1, occludin, LPS, systemic inflammatory cytokines, neuropsychological assessment, and clinical characteristics.ResultsThere was a lower Chao1 index in the SCD group (P = 0.004) and differences in beta diversity among the three groups (PCA: P = 0.026, PCoA: P= 0.004). The relative abundance of Bacteroidetes was higher in the SCD group (P = 0.016, P = 0.008), and Firmicutes were more enriched in the aMCI group than in the SCD group (P= 0.026). At the family level, the total abundance of Gram-negative bacteria was higher in the SCD group than in the aMCI group (P = 0.047), and the Christensenellaceae family was detected at lower levels in the SCD and aMCI groups than in the NC group (P= 0.039). At the genus level, the eleven short-chain fatty acid (SCFA)-producing bacteria exhibited differences among the three groups. PICRUSt analysis showed that the pathways involved in SCFA catabolism, biosynthesis, and adherent junctions were reduced in SCD patients, and lipid synthesis proteins were reduced in pAD patients. Meanwhile, elevated plasma LPS and CRP were observed in SCD patients, and higher plasma occludin in aMCI patients. The IM was correlated with plasma claudin-1, LPS, inflammatory factors, neuropsychological assessment, and clinical characteristics.ConclusionThe intestines of SCD and aMCI patients preoperatively exhibited IM dysbiosis and barrier dysfunction, and elevated plasma LPS and CRP were observed in SCD patients.

Fructose-Induced Intestinal Microbiota Shift Following Two Types of Short-Term High-Fructose Dietary Phases.

High consumption of fructose and high-fructose corn syrup is related to the development of obesity-associated metabolic diseases, which have become the most relevant diet-induced diseases. However, the influences of a high-fructose diet on gut microbiota are still largely unknown. We therefore examined the effect of short-term high-fructose consumption on the human intestinal microbiota. Twelve healthy adult women were enrolled in a pilot intervention study. All study participants consecutively followed four different diets, first a low fructose diet (< 10 g/day fructose), then a fruit-rich diet (100 g/day fructose) followed by a low fructose diet (10 g/day fructose) and at last a high-fructose syrup (HFS) supplemented diet (100 g/day fructose). Fecal microbiota was analyzed by 16S rRNA sequencing. A high-fructose fruit diet significantly shifted the human gut microbiota by increasing the abundance of the phylum Firmicutes, in which beneficial butyrate producing bacteria such as Faecalibacterium, Anareostipes and Erysipelatoclostridium were elevated, and decreasing the abundance of the phylum Bacteroidetes including the genus Parabacteroides. An HFS diet induced substantial differences in microbiota composition compared to the fruit-rich diet leading to a lower Firmicutes and a higher Bacteroidetes abundance as well as reduced abundance of the genus Ruminococcus. Compared to a low-fructose diet we observed a decrease of Faecalibacterium and Erysipelatoclostridium after the HFS diet. Abundance of Bacteroidetes positively correlated with plasma cholesterol and LDL level, whereas abundance of Firmicutes was negatively correlated. Different formulations of high-fructose diets induce distinct alterations in gut microbiota composition. High-fructose intake by HFS causes a reduction of beneficial butyrate producing bacteria and a gut microbiota profile that may affect unfavorably host lipid metabolism whereas high consumption of fructose from fruit seems to modulate the composition of the gut microbiota in a beneficial way supporting digestive health and counteracting harmful effects of excessive fructose.

The influences of low protein diet on the intestinal microbiota of mice

Recent research suggests that protein deficiency symptoms are influenced by the intestinal microbiota. We investigated the influence of low protein diet on composition of the intestinal microbiota through animal experiments. Specific pathogen-free (SPF) mice were fed one of four diets (3, 6, 9, or 12% protein) for 4 weeks (n = 5 per diet). Mice fed the 3% protein diet showed protein deficiency symptoms such as weight loss and low level of blood urea nitrogen concentration in their serum. The intestinal microbiota of mice in the 3% and 12% protein diet groups at day 0, 7, 14, 21 and 28 were investigated by 16S rRNA gene sequencing, which revealed differences in the microbiota. In the 3% protein diet group, a greater abundance of urease producing bacterial species was detected across the duration of the study. In the 12% diet protein group, increases of abundance of Streptococcaceae and Clostridiales families was detected. These results suggest that protein deficiency may be associated with shifts in intestinal microbiota.

Corrigendum to “Long‐Term Potable Effects of Alkalescent Mineral Water on Intestinal Microbiota Shift and Physical Conditioning”

[This corrects the article DOI: 10.1155/2019/2710587.].

Long-Term Potable Effects of Alkalescent Mineral Water on Intestinal Microbiota Shift and Physical Conditioning.

Background An alkalescent (pH 8.3) mineral water (AMW) of Hita basin, located in the northwestern part of Kyushu island in Japan, has been recognized for the unique quality of ingredients including highly concentrated silicic acid, sodium, potassium, and hydrogen carbonate. The biological effects of AMW intake were evaluated with a particular focus on its “antiobesity” properties through its modulation of the gut microbiota population. Methods Two groups of C57BL6/J mice (8-week-old male) were maintained with a standard diet and tap water (control: TWC group) or AMW (AMW group) for 6 months and the following outputs were quantitated: (1) food and water intake, (2) body weight (weekly), (3) body fat measurements by CT scan (monthly), (4) sera biochemical values (TG, ALT, AST, and ALP), and (5) UCP-1 mRNA in fat tissues (terminal point). Two groups of ICR mice (7-week-old male) were maintained with the same method and their feces were collected at the 0, 1st, 3rd, and 6th month at which time the population rates of gut microbiota were quantitated using metagenomic sequencing analysis of 16S-rRNA. Results Among all antiobesity testing items, even though a weekly dietary consumption was increased (p=0.012), both ratios of weight gain (p=1.21E − 10) and visceral fat accumulation (p=0.029) were significantly reduced in the AMW group. Other criteria including water intake (p=0.727), the amounts of total (p=0.1602), and subcutaneous fat accumulation (p=0.052) were within the margin of error and UCP-1 gene expression level (p=0.171) in the AMW group was 3.89-fold higher than that of TWC. Among 8 major gut bacteria families, Lactobacillaceae (increased, p=0.029) and Clostridiaceae (decreased, p=0.029) showed significant shift in the whole population. Conclusion We observed significantly reduced (1) weight gaining ratio (average −1.86%, up to −3.3%), (2) visceral fat accumulation ratio (average −4.30%, up to −9.1%), and (3) changes in gut microbiota population. All these consequences could support the “health benefit” functionality of AMW.

High-fat diet intake modulates maternal intestinal adaptations to pregnancy and results in placental hypoxia, as well as altered fetal gut barrier proteins and immune markers.

Maternal obesity has been associated with shifts in intestinal microbiota, which may contribute to impaired barrier function Impaired barrier function may expose the placenta and fetus to pro-inflammatory mediators We investigated the impacts of diet-induced obesity in mice on maternal and fetal intestinal structure and placental vascularization Diet-induced obesity decreased maternal intestinal short chain fatty acids and their receptors, impaired gut barrier integrity and was associated with fetal intestinal inflammation. Placenta from obese mothers showed blood vessel immaturity, hypoxia, increased transcript levels of inflammation, autophagy and altered levels of endoplasmic reticulum stress markers. These data suggest that maternal intestinal changes probably contribute to adverse placental adaptations and also impart an increased risk of obesity in the offspring via alterations in fetal gut development. Shifts in maternal intestinal microbiota have been implicated in metabolic adaptations to pregnancy. In the present study, we generated cohorts of female C57BL/6J mice fed a control (17%kcal fat, n=10-14) or a high-fat diet (HFD 60%kcal from fat, n=10-14; ad libitum) aiming to investigate the impact on the maternal gut microbiota, intestinal inflammation and gut barrier integrity, placental inflammation and fetal intestinal development at embryonic day 18.5. HFD was associated with decreased relative abundances of short-chain fatty acid (SCFA) producing genera during pregnancy. These diet-induced shifts paralleled decreased maternal intestinal mRNA levels of SCFA receptor Gpr41, modestly decreased cecal butyrate, and altered mRNA levels of inflammatory cytokines and immune cell markers in the maternal intestine. Maternal HFD resulted in impaired gut barrier integrity, with corresponding increases in circulating maternal levels of lipopolysaccharide (LPS) and tumour necrosis factor. Placentas from HFD dams demonstrated blood vessel immaturity and hypoxia; decreased free carnitine, acylcarnitine derivatives and trimethylamine-N-oxide; and altered mRNA levels of inflammation, autophagy, and ER stress markers. HFD exposed fetuses had increased activation of nuclear factor-kappa B and inhibition of the unfolded protein response in the developing intestine. Taken together, these data suggest that HFD intake prior to and during pregnancy shifts the composition of the maternal gut microbiota and impairs gut barrier integrity, resulting in increased maternal circulating LPS, which may ultimate contribute to changes in placental vascularization and fetal gut development.

Shifts in intestinal microbiota after duodenal exclusion favor glycemic control and weight loss: a randomized controlled trial

BackgroundIn recent years, studies indicate gut microbiota as an important modulator in the pathophysiology of type 2 diabetes. Environmental and genetic factors interact to control the host's intestinal microbiota, triggering metabolic disorders such as obesity and insulin resistance. ObjectivesThe objective of this study was to identify the fecal microbiota in adult type 2 diabetes patients and to assess changes in composition after metabolic surgery. SettingUniversity Hospital of the University of São Paulo. MethodsTwenty-one patients were enrolled in a randomized controlled study divided into 2 arms. One group underwent duodenal-jejunal bypass surgery with minimal gastric resection, and fecal samples were collected before the operation and after 6 and 12 months. The other group received medical care (standard care group) and was followed for 12 months. Fecal samples were collected at baseline and after 6 and 12 months. Fecal microbiota was analyzed using high-throughput sequencing with V4 16 S rRNA primers. ResultsThe fecal microbiota in duodenal-jejunal bypass surgery with minimal gastric resection group (Bacteroides, Akkermansia, and Dialister) exhibited increased abundance and diversity compared with that in the standard care group; however, the increase in A. muciniphila was only statistically significant in the surgical group, probably due to the study's small sample size. ConclusionsThe data presented suggest that duodenal-jejunal bypass surgery with minimal gastric resection increases microbial richness and abundancy, mainly for those bacteria related to weight loss and metabolic control (Akkermansia), providing a better understanding of the role of microbiota in type 2 diabetes regulation and its changes after metabolic surgery.

The Features of Fecal and Ileal Mucosa-Associated Microbiota in Dairy Calves during Early Infection with Mycobacterium avium Subspecies paratuberculosis.

Current diagnostic tests for Johne's disease (JD), a chronic granulomatous inflammation of the gastrointestinal tract of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), lack the sensitivity to identify infected animals at early (asymptomatic) stages of the disease. The objective was to determine the pattern of MAP-associated dysbiosis of intestinal microbiota as a potential biomarker for early detection of infected cattle. To that end, genomic DNA was extracted from ileal mucosa and fecal samples collected from 28 MAP-positive and five control calves. High-throughput Illumina sequencing of the V4 hypervariable region of the 16S rRNA gene was used for community profiling of ileal mucosa-associated (MAM) or fecal microbiota. The PERMANOVA analysis of unweighted UniFrac distances revealed distinct clustering of ileal MAM (P = 0.049) and fecal microbiota (P = 0.068) in MAP-infected vs. control cattle. Microbiota profile of MAP-infected animals was further investigated by linear discriminant analysis effective size (LEfSe); several bacterial taxa within the phylum Proteobacteria were overrepresented in ileal MAM of control calves. Moreover, based on reconstructed metagenomes (PICRUSt) of ileal MAM, functional pathways associated with MAP infection were inferred. Enrichment of lysine and histidine metabolism pathways, and underrepresentation of glutathione metabolism and leucine and isoleucine degradation pathways in MAP-infected calves suggested potential contributions of ileal MAM in development of intestinal inflammation. Finally, simultaneous overrepresentation of families Planococcaceae and Paraprevotellaceae, as well as underrepresentation of genera Faecalibacterium and Akkermansia in the fecal microbiota of infected cattle, served as potential biomarker for identifying infected cattle during subclinical stages of JD. Collectively, based on compositional and functional shifts in intestinal microbiota of infected cattle, we inferred that this dynamic network of microorganisms had an active role in intestinal homeostasis.

Resistant potato starches (type 4 RS) exhibit varying effects on laxation with and without phylum level changes in microbiota: A randomised trial in young adults

The effects of resistant potato starches on gastrointestinal (GI) function and microbiota in healthy individuals were investigated. In a 6-week, double-blind, cross-over study, subjects (N = 57; 21M; 36F) were randomised to consume 30 g fibre/d from one of three chemically modified potato starches (RS4-A, soluble, viscous; RS4-B, soluble, non-viscous; RS4-C, insoluble, non-viscous) and control in beverages for 2 weeks with a 1-week washout and daily reporting of stool frequency, Bristol Stool Form Scale (BSFS), GI symptoms and compliance. Faecal microbiota was analysed by qPCR and 16S rRNA sequencing. Stool frequency and BSFS increased only with RS4-B (P < 0.01). GI symptoms were minimal with slight increases in flatulence with all interventions (P < 0.001). There were no changes in Lactobacillus or Bifidobacteria spp. However, RS4-B decreased Firmicutes (P = 0.02) and the ratio of Firmicutes to Bacteroidetes (P = 0.01). Resistant potato starches vary in their effects on GI function, which may be related to shifts in intestinal microbiota.

Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM-2 Ingestion Induces a Less Inflammatory Cytokine Profile and a Potentially Beneficial Shift in Gut Microbiota in Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study

Objective: This study determined whether older adults who consumed a probiotic mixture would have a greater proportion of circulating CD4+ lymphocytes, altered cytokine production, and a shift in intestinal microbiota toward a healthier microbial community.Methods: Participants (70 ± 1 years [mean ± SEM]; n = 32) consumed a probiotic (Lactobacillus gasseri KS-13, Bifidobacterium bifidum G9-1, and Bifidobacterium longum MM2) or a placebo twice daily for 3 weeks with a 5-week washout period between intervention periods. Blood and stools were collected before and after each intervention. The percentage of circulating CD4+ lymphocytes and ex vivo mitogen-stimulated cell cytokine production were measured. In stools, specific bacterial targets were quantified via quantitative polymerase chain reaction (qPCR) and community composition was determined via pyrosequencing.Results: During the first period of the crossover the percentage of CD4+ cells decreased with the placebo (48% ± 3% to 31% ± 3%, p < 0.01) but did not change with the probiotic (44% ± 3% to 42% ± 3%) and log-transformed concentrations of interleukin-10 increased with the probiotic (1.7 ± 0.2 to 3.4 ± 0.2, p < 0.0001) but not the placebo (1.7 ± 0.2 to 2.1 ± 0.2). With the probiotic versus the placebo a higher percentage of participants had an increase in fecal bifidobacteria (48% versus 30%, p < 0.05) and lactic acid bacteria (55% versus 43%, p < 0.05) and a decrease in Escherichia coli (52% versus 27%, p < 0.05). Several bacterial groups matching Faeacalibactierium prausnitzii were more prevalent in stool samples with the probiotic versus placebo.Conclusions: The probiotic maintained CD4+ lymphocytes and produced a less inflammatory cytokine profile possibly due to the changes in the microbial communities, which more closely resembled those reported in healthy younger populations.

16S rRNA Gene Pyrosequencing Reveals Shift in Patient Faecal Microbiota During High-Dose Chemotherapy as Conditioning Regimen for Bone Marrow Transplantation

Gastrointestinal disturbances are a side-effect frequently associated with haematological malignancies due to the intensive cytotoxic treatment given in connection with bone marrow transplantation (BMT). However, intestinal microbiota changes during chemotherapy remain poorly described, probably due to the use of culture-based and low-resolution molecular methods in previous studies. The objective of our study was to apply a next generation DNA sequencing technology to analyse chemotherapy-induced changes in faecal microbiota. We included eight patients with non-Hodgkin's lymphoma undergoing one course of BMT conditioning chemotherapy. We collected a prechemotherapy faecal sample, the day before chemotherapy was initiated, and a postchemotherapy sample, collected 1 week after the initiation of chemotherapy. Total DNA was extracted from faecal samples, denaturing high-performance liquid chromatography based on amplification of the V6 to V8 region of the 16S ribosomal RNA (rRNA) gene, and 454-pyrosequencing of the 16 S rRNA gene, using PCR primers targeting the V5 and V6 hypervariable 16S rRNA gene regions were performed. Raw sequence data were screened, trimmed, and filtered using the QIIME pipeline. We observed a steep reduction in alpha diversity and significant differences in the composition of the intestinal microbiota in response to chemotherapy. Chemotherapy was associated with a drastic drop in Faecalibacterium and accompanied by an increase of Escherichia. The chemotherapy-induced shift in the intestinal microbiota could induce severe side effects in immunocompromised cancer patients. Our study is a first step in identifying patients at risk for gastrointestinal disturbances and to promote strategies to prevent this drastic shift in intestinal microbiota.

Intestinal epithelial cell apoptosis and loss of barrier function in the setting of altered microbiota with enteral nutrient deprivation

Total parenteral nutrition (TPN), a commonly used treatment for patients who cannot receive enteral nutrition, is associated with significant septic complications due in part to a loss of epithelial barrier function (EBF). While the underlying mechanisms of TPN-related epithelial changes are poorly understood, a mouse model of TPN-dependence has helped identify several contributing factors. Enteral deprivation leads to a shift in intestinal microbiota to predominantly Gram-negative Proteobacteria. This is associated with an increase in expression of proinflammatory cytokines within the mucosa, including interferon-γ and tumor necrosis factor-α. A concomitant loss of epithelial growth factors leads to a decrease in epithelial cell proliferation and increased apoptosis. The resulting loss of epithelial tight junction proteins contributes to EBF dysfunction. These mechanisms identify potential strategies of protecting against TPN-related complications, such as modification of luminal bacteria, blockade of proinflammatory cytokines, or growth factor replacement.

Modification of Intestinal Microbiota and Its Consequences for Innate Immune Response in the Pathogenesis of Campylobacteriosis

Campylobacter jejuni is the leading cause of bacterial food-borne gastroenteritis in the world, and thus one of the most important public health concerns. The initial stage in its pathogenesis after ingestion is to overcome colonization resistance that is maintained by the human intestinal microbiota. But how it overcomes colonization resistance is unknown. Recently developed humanized gnotobiotic mouse models have provided deeper insights into this initial stage and host's immune response. These studies have found that a fat-rich diet modifies the composition of the conventional intestinal microbiota by increasing the Firmicutes and Proteobacteria loads while reducing the Actinobacteria and Bacteroidetes loads creating an imbalance that exposes the intestinal epithelial cells to adherence. Upon adherence, deoxycholic acid stimulates C. jejuni to synthesize Campylobacter invasion antigens, which invade the epithelial cells. In response, NF-κB triggers the maturation of dendritic cells. Chemokines produced by the activated dendritic cells initiate the clearance of C. jejuni cells by inducing the actions of neutrophils, B-lymphocytes, and various subsets of T-cells. This immune response causes inflammation. This review focuses on the progress that has been made on understanding the relationship between intestinal microbiota shift, establishment of C. jejuni infection, and consequent immune response.

Total Parenteral Nutrition Induces a Shift in the Firmicutes to Bacteroidetes Ratio in Association with Paneth Cell Activation in Rats ,2

The use of total parenteral nutrition (TPN) in the treatment of critically ill patients has been the subject of debate because it has been associated with disturbances in intestinal homeostasis. Important factors in maintaining intestinal homeostasis are the intestinal microbiota and Paneth cells, which exist in a mutually amendable relationship. We hypothesized that the disturbed intestinal homeostasis in TPN-fed individuals results from an interplay between a shift in microbiota composition and alterations in Paneth cells. We studied the microbiota composition and expression of Paneth cell antimicrobial proteins in rats receiving TPN or a control diet for 3, 7, or 14 d. qPCR analysis of DNA extracts from small intestinal luminal contents of TPN-fed rats showed a shift in the Firmicutes:Bacteroidetes ratio in favor of Bacteroidetes after 14 d (P < 0.05) compared with the control group. This finding coincided with greater staining intensity for lysozyme and significantly greater mRNA expression of the Paneth cell antimicrobial proteins lysozyme (P < 0.05), rat α-defensin 5 (P < 0.01), and rat α-defensin 8 (P < 0.01). Finally, 14 d of TPN resulted in greater circulating ileal lipid-binding protein concentrations (P < 0.05) and greater leakage of horseradish peroxidase (P < 0.01), which is indicative of enterocyte damage and a breached intestinal barrier. Our findings show a shift in intestinal microbiota in TPN-fed rats that correlated with changes in Paneth cell lysozyme expression (rs = −0.75, P < 0.01). Further studies that include interventions with microbiota or nutrients that modulate them may yield information on the involvement of the microbiota and Paneth cells in TPN-associated intestinal compromise.

Weaning diet induces sustained metabolic phenotype shift in the pig and influences host response to Bifidobacterium lactis NCC2818

BackgroundThe process of weaning causes a major shift in intestinal microbiota and is a critical period for developing appropriate immune responses in young mammals.ObjectiveTo use a new systems approach to...

Phylotype-level 16S rRNA analysis reveals new bacterial indicators of health state in acute murine colitis

Human inflammatory bowel disease and experimental colitis models in mice are associated with shifts in intestinal microbiota composition, but it is unclear at what taxonomic/phylogenetic level such microbiota dynamics can be indicative for health or disease. Here, we report that dextran sodium sulfate (DSS)-induced colitis is accompanied by major shifts in the composition and function of the intestinal microbiota of STAT1(-/-) and wild-type mice, as determined by 454 pyrosequencing of bacterial 16S rRNA (gene) amplicons, metatranscriptomics and quantitative fluorescence in situ hybridization of selected phylotypes. The bacterial families Ruminococcaceae, Bacteroidaceae, Enterobacteriaceae, Deferribacteraceae and Verrucomicrobiaceae increased in relative abundance in DSS-treated mice. Comparative 16S rRNA sequence analysis at maximum possible phylogenetic resolution identified several indicator phylotypes for DSS treatment, including the putative mucin degraders Akkermansia and Mucispirillum. The analysis additionally revealed strongly contrasting abundance changes among phylotypes of the same family, particularly within the Lachnospiraceae. These extensive phylotype-level dynamics were hidden when reads were grouped at higher taxonomic levels. Metatranscriptomic analysis provided insights into functional shifts in the murine intestinal microbiota, with increased transcription of genes associated with regulation and cell signaling, carbohydrate metabolism and respiration and decreased transcription of flagellin genes during inflammation. These findings (i) establish the first in-depth inventory of the mouse gut microbiota and its metatranscriptome in the DSS colitis model, (ii) reveal that family-level microbial community analyses are insufficient to reveal important colitis-associated microbiota shifts and (iii) support a scenario of shifting intra-family structure and function in the phylotype-rich and phylogenetically diverse Lachnospiraceae in DSS-treated mice.