Effects of treatment with three antibiotics, vancomycin, neomycin, and AVNM on gut microbiome in C57BL/6 mice

AbstractHigher organisms, especially mammals, harbor diverse microbiota in the gut that plays a major role in maintaining health and physiological homeostasis. Perturbation of gut flora helps identifying their roles. Antibiotics are potent perturbing agents of microbiome. Select antibiotics like vancomycin, neomycin, and AVNM (an antibiotic cocktail containing ampicillin, vancomycin, neomycin, and metronidazole) were used to perturb the gut microbiota of C57BL/6 male mice to understand their roles in host immunity and metabolism. The current study revealed that the resulting gut microbial composition was different, and diversity (at the phylum and genus level) was reduced differentially following each antibiotic treatment. Vancomycin treatment caused a significant increase in Verrucomicrobia and Proteobacteria phyla. The treatment with neomycin yielded an increase in the Bacteroidetes phylum, while the treatment with AVNM led to an increase in Proteobacteria phylum with lowest diversity of microbiome in the gut. The current results also revealed that the different antibiotics treatment caused variation in the cecal index, expression of immune genes (TNF-α, IL-10, IFN-γ) in the colon, and short-chain fatty acids (SCFA) level in the blood of mice. A strong correlation was observed for antibiotic-induced differential dysbiosis patterns of gut microbiota and the altered immune and SCFA profile of the host. The outcome of the present study could be clinically important.

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Probiotic Supplementation in a Clostridium difficile-Infected Gastrointestinal Model Is Associated with Restoring Metabolic Function of Microbiota

Microorganisms ◽

10.3390/microorganisms8010060 ◽

2019 ◽

Vol 8 (1) ◽

pp. 60

Author(s):

Mohd Baasir Gaisawat ◽

Chad W. MacPherson ◽

Julien Tremblay ◽

Amanda Piano ◽

Michèle M. Iskandar ◽

...

Keyword(s):

Gut Microbiota ◽

Alpha Diversity ◽

Gastrointestinal Disorder ◽

Short Chain Fatty Acids ◽

Rrna Gene ◽

Metabolic Function ◽

Microbial Composition ◽

Single Strain ◽

Fecal Samples ◽

Metabolic Functions

Clostridium (C.) difficile-infection (CDI), a nosocomial gastrointestinal disorder, is of growing concern due to its rapid rise in recent years. Antibiotic therapy of CDI is associated with disrupted metabolic function and altered gut microbiota. The use of probiotics as an adjunct is being studied extensively due to their potential to modulate metabolic functions and the gut microbiota. In the present study, we assessed the ability of several single strain probiotics and a probiotic mixture to change the metabolic functions of normal and C. difficile-infected fecal samples. The production of short-chain fatty acids (SCFAs), hydrogen sulfide (H2S), and ammonia was measured, and changes in microbial composition were assessed by 16S rRNA gene amplicon sequencing. The C. difficile-infection in fecal samples resulted in a significant decrease (p < 0.05) in SCFA and H2S production, with a lower microbial alpha diversity. All probiotic treatments were associated with significantly increased (p < 0.05) levels of SCFAs and restored H2S levels. Probiotics showed no effect on microbial composition of either normal or C. difficile-infected fecal samples. These findings indicate that probiotics may be useful to improve the metabolic dysregulation associated with C. difficile infection.

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Gut-brain Axis: Role of Lipids in the Regulation of Inflammation, Pain and CNS Diseases

Current Medicinal Chemistry ◽

10.2174/0929867324666170216113756 ◽

2018 ◽

Vol 25 (32) ◽

pp. 3930-3952 ◽

Cited By ~ 49

Author(s):

Roberto Russo ◽

Claudia Cristiano ◽

Carmen Avagliano ◽

Carmen De Caro ◽

Giovanna La Rana ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Irritable Bowel Syndrome ◽

Gut Microbiota ◽

Short Chain Fatty Acids ◽

Nervous System Diseases ◽

Central Nervous System Diseases ◽

Bioactive Lipids ◽

Microbial Composition ◽

Irritable Bowel

The human gut is a composite anaerobic environment with a large, diverse and dynamic enteric microbiota, represented by more than 100 trillion microorganisms, including at least 1000 distinct species. The discovery that a different microbial composition can influence behavior and cognition, and in turn the nervous system can indirectly influence enteric microbiota composition, has significantly contributed to establish the well-accepted concept of gut-brain axis. This hypothesis is supported by several evidence showing mutual mechanisms, which involve the vague nerve, the immune system, the hypothalamic-pituitaryadrenal (HPA) axis modulation and the bacteria-derived metabolites. Many studies have focused on delineating a role for this axis in health and disease, ranging from stress-related disorders such as depression, anxiety and irritable bowel syndrome (IBS) to neurodevelopmental disorders, such as autism, and to neurodegenerative diseases, such as Parkinson Disease, Alzheimer’s Disease etc. Based on this background, and considering the relevance of alteration of the symbiotic state between host and microbiota, this review focuses on the role and the involvement of bioactive lipids, such as the N-acylethanolamine (NAE) family whose main members are N-arachidonoylethanolamine (AEA), palmitoylethanolamide (PEA) and oleoilethanolamide (OEA), and short chain fatty acids (SCFAs), such as butyrate, belonging to a large group of bioactive lipids able to modulate peripheral and central pathologic processes. Their effective role has been studied in inflammation, acute and chronic pain, obesity and central nervous system diseases. A possible correlation has been shown between these lipids and gut microbiota through different mechanisms. Indeed, systemic administration of specific bacteria can reduce abdominal pain through the involvement of cannabinoid receptor 1 in the rat; on the other hand, PEA reduces inflammation markers in a murine model of inflammatory bowel disease (IBD), and butyrate, producted by gut microbiota, is effective in reducing inflammation and pain in irritable bowel syndrome and IBD animal models. In this review, we underline the relationship among inflammation, pain, microbiota and the different lipids, focusing on a possible involvement of NAEs and SCFAs in the gut-brain axis and their role in the central nervous system diseases.

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Nutritional combinatorial impact on the gut microbiota and plasma short-chain fatty acids levels in the prevention of mammary cancer in Her2/neu estrogen receptor-negative transgenic mice

PLoS ONE ◽

10.1371/journal.pone.0234893 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0234893

Author(s):

Manvi Sharma ◽

Itika Arora ◽

Matthew L. Stoll ◽

Yuanyuan Li ◽

Casey D. Morrow ◽

...

Keyword(s):

Breast Cancer ◽

Fatty Acids ◽

Estrogen Receptor ◽

Gut Microbiota ◽

Transgenic Mice ◽

Dietary Treatment ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Microbial Composition ◽

Estrogen Receptor Negative

Breast cancer is the second leading cause of cancer-related mortality in women. Various nutritional compounds possess anti-carcinogenic properties which may be mediated through their effects on the gut microbiota and its production of short-chain fatty acids (SCFAs) for the prevention of breast cancer. We evaluated the impact of broccoli sprouts (BSp), green tea polyphenols (GTPs) and their combination on the gut microbiota and SCFAs metabolism from the microbiota in Her2/neu transgenic mice that spontaneously develop estrogen receptor-negative [ER(-)] mammary tumors. The mice were grouped based on the dietary treatment: control, BSp, GTPs or their combination from beginning in early life (BE) or life-long from conception (LC). We found that the combination group showed the strongest inhibiting effect on tumor growth volume and a significant increase in tumor latency. BSp treatment was integrally more efficacious than the GTPs group when compared to the control group. There was similar clustering of microbiota of BSp-fed mice with combination-fed mice, and GTPs-fed mice with control-fed mice at pre-tumor in the BE group and at pre-tumor and post-tumor in the LC group. The mice on all dietary treatment groups incurred a significant increase of Adlercreutzia, Lactobacillus genus and Lachnospiraceae, S24-7 family in the both BE and LC groups. We found no change in SCFAs levels in the plasma of BSp-fed, GTPs-fed and combination-fed mice of the BE group. Marked changes were observed in the mice of the LC group consisting of significant increases in propionate and isobutyrate in GTPs-fed and combination-fed mice. These studies indicate that nutrients such as BSp and GTPs differentially affect the gut microbial composition in both the BE and LC groups and the key metabolites (SCFAs) levels in the LC group. The findings also suggest that temporal factors related to different time windows of consumption during the life-span can have a promising influence on the gut microbial composition, SCFAs profiles and ER(-) breast cancer prevention.

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The gut microbiota of environmentally enriched mice regulates visual cortical plasticity

10.1101/2021.07.16.452307 ◽

2021 ◽

Author(s):

Leonardo Lupori ◽

Sara Cornuti ◽

Raffaele M Mazziotti ◽

Elisa Borghi ◽

Emerenziana Ottaviano ◽

...

Keyword(s):

Gut Microbiota ◽

Cortical Plasticity ◽

Brain Plasticity ◽

Ocular Dominance ◽

Standard Condition ◽

Intestinal Bacteria ◽

Short Chain Fatty Acids ◽

The Body ◽

Antibiotic Cocktail ◽

Visual Cortical

Exposing animals to an enriched environment (EE) has dramatic effects on brain structure, function and plasticity. The poorly known "EE derived signals" mediating the EE effects are thought to be generated within the central nervous system. Here, we shift the focus to the body periphery, revealing that gut microbiota signals are crucial for EE-driven plasticity. Developmental analysis of intestinal bacteria composition in EE mice revealed striking differences from standard condition (ST) animals and enhanced levels of short-chain fatty acids (SCFA). Depleting the EE mice gut microbiota with an antibiotic cocktail decreased SCFA and prevented EE induction of adult ocular dominance (OD) plasticity, spine dynamics and microglia rearrangement. SCFA treatment in ST mice mimicked the EE induction of adult OD plasticity and morphological microglial rearrangement. Remarkably, transferring the microbiota of EE mice to ST recipients activated adult OD plasticity. Thus, taken together our data suggest that experience-dependent changes in gut microbiota regulate brain plasticity.

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Short-Term Lincomycin Exposure Depletion of Murine Microbiota Affects Short-Chain Fatty Acids and Intestinal Morphology and Immunity

Antibiotics ◽

10.3390/antibiotics9120907 ◽

2020 ◽

Vol 9 (12) ◽

pp. 907

Author(s):

Shunfen Zhang ◽

Ruqing Zhong ◽

Hui Han ◽

Bao Yi ◽

Jie Yin ◽

...

Keyword(s):

Body Weight Gain ◽

Short Chain Fatty Acids ◽

Isobutyric Acid ◽

The Body ◽

Intestinal Morphology ◽

Short Term ◽

Microbial Composition ◽

Relative Expression ◽

Depletion Effect ◽

Tnf Α

Lincomycin, as one of the most commonly used antibiotics, may cause intestinal injury, enteritis and other side effects, but it remains unknown whether these effects are associated with microbial changes and the effects of different doses of lincomycin on infants. Here, 21-day old mice were exposed to 1 and 5 g/L lincomycin to explore the effects of lincomycin on the gut microbiota, metabolites and inflammation. Compared to the control mice, 1 g/L lincomycin exposure decreased the body weight gain of mice (p < 0.05). Both 1 and 5 g/L lincomycin exposure reduced the diversity and microbial composition of mice (p < 0.05). Furthermore, 1 and 5 g/L lincomycin reduced the relative concentrations of acetate, propionate, butyrate, valerate, isobutyric acid and isovaleric acid in the colon chyme of mice (p < 0.05). In addition, 5 g/L lincomycin exposure reduced the villus height, crypt depth, and relative expression of TLR2, TLR3, TLR4, IL-18, TNF-α, and p65 in the jejunum of mice (p < 0.05), while 1 g/L lincomycin exposure reduced the relative expression of TLR2, TLR3, TNF-α, and p65 (p < 0.05). Collectively, these results highlight the depletion effect of short-term lincomycin exposure on microbiota and the further regulatory effect on intestinal morphology and immunosuppression in infant mice.

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Associations between disordered gut microbiota and changes of neurotransmitters and short-chain fatty acids in depressed mice

Translational Psychiatry ◽

10.1038/s41398-020-01038-3 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Min Wu ◽

Tian Tian ◽

Qiang Mao ◽

Tao Zou ◽

Chan-juan Zhou ◽

...

Keyword(s):

Fatty Acids ◽

Acetic Acid ◽

Gut Microbiota ◽

Molecular Mechanisms ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Rrna Gene ◽

Microbial Composition ◽

Fecal Samples ◽

Chain Fatty Acids

Abstract Mounting evidence suggests that gut microbiota can play an important role in pathophysiology of depression, but its specific molecular mechanisms are still unclear. This study was conducted to explore the associations between changes in neurotransmitters and short-chain fatty acids (SCFAs) and altered gut microbiota in depressed mice. Here, the chronic restraint stress (CRS) model of depression was built. The classical behavioral tests were conducted to assess the depressive-like behaviors of mice. The 16S rRNA gene sequence extracted from fecal samples was used to assess the gut microbial composition. Liquid and gas chromatography mass spectroscopy were used to identify neurotransmitters in hypothalamus and SCFAs in fecal samples, respectively. Finally, 29 differential bacteria taxa between depressed mice and control mice were identified, and the most differentially abundant bacteria taxa were genus Allobaculum and family Ruminococcaceae between the two groups. The acetic acid, propionic acid, pentanoic acid, norepinephrine, 5-HIAA and 5-HT were significantly decreased in depressed mice compared to control mice. Genus Allobaculum was found to be significantly positively correlated with acetic acid and 5-HT. Taken together, these results provided novel microbial and metabolic frameworks for understanding the role of microbiota-gut-brain axis in depression, and suggested new insights to pave the way for novel therapeutic methods.

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Shifts in microbiota species and fermentation products in a dietary model enriched in fat and sucrose

Beneficial Microbes ◽

10.3920/bm2013.0097 ◽

2015 ◽

Vol 6 (1) ◽

pp. 97-111 ◽

Cited By ~ 23

Author(s):

U. Etxeberria ◽

N. Arias ◽

N. Boqué ◽

M.T. Macarulla ◽

M.P. Portillo ◽

...

Keyword(s):

Gut Microbiota ◽

Bacterial Species ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Gas Chromatography Mass Spectrometry ◽

Intestinal Barrier Function ◽

Microbial Composition ◽

Fermentation Products ◽

Inflammatory Status ◽

Male Wistar Rats

The gastrointestinal tract harbours a ‘superorganism’ called the gut microbiota, which is known to play a crucial role in the onset and development of diverse diseases. This internal ecosystem, far from being a static environment, can be manipulated by diet and dietary components. Feeding animals with high-fat sucrose (HFS) diets entails diet-induced obesity, a model which is usually used in research to mimic the obese phenotype of Western societies. The aim of the present study was to identify gut microbiota dysbiosis and associated metabolic changes produced in male Wistar rats fed a HFS diet for 6 weeks and compare it with the basal microbial composition. For this purpose, DNA extracted from faeces at baseline and after treatment was analysed by amplification of the V4-V6 region of the 16S ribosomal DNA (rDNA) gene using 454 pyrosequencing. Short-chain fatty acids, i.e. acetate, propionate and butyrate, were also evaluated by gas chromatography-mass spectrometry. At the end of the treatment, gut microbiota composition significantly differed at phylum level (Firmicutes, Bacteroidetes and Proteobacteria) and class level (Erisypelotrichi, Deltaproteobacteria, Bacteroidia and Bacilli). Interestingly, the class Clostridia showed a significant decrease after HFS diet treatment, which correlated with visceral adipose tissue, and is likely mediated by dietary carbohydrates. Of particular interest, Clostridium cluster XIVa species were significantly reduced and changes were identified in the relative abundance of other specific bacterial species (Mitsuokella jalaludinii, Eubacterium ventriosum, Clostridium sp. FCB90-3, Prevotella nanceiensis, Clostridium fusiformis, Clostridium sp. BNL1100 and Eubacterium cylindroides) that, in some cases, showed opposite trends to their relative families. These results highlight the relevance of characterising gut microbial population differences at species level and contribute to understand the plausible link between diet and specific gut bacterial species that are able to influence the inflammatory status, intestinal barrier function and obesity development.

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Barley Leaf Insoluble Dietary Fiber Alleviated Dextran Sulfate Sodium-Induced Mice Colitis by Modulating Gut Microbiota

Nutrients ◽

10.3390/nu13030846 ◽

2021 ◽

Vol 13 (3) ◽

pp. 846

Author(s):

Meiling Tian ◽

Daotong Li ◽

Chen Ma ◽

Yu Feng ◽

Xiaosong Hu ◽

...

Keyword(s):

Gut Microbiota ◽

Dietary Fiber ◽

Intestinal Microbiota ◽

Short Chain Fatty Acids ◽

Soluble Dietary Fiber ◽

Insoluble Dietary Fiber ◽

Tnf Α ◽

Barley Leaf ◽

Inflammatory Bowel ◽

Secondary Bile Acids

Supplementation of dietary fiber has been proved to be an effective strategy to prevent and relieve inflammatory bowel disease (IBD) through gut microbiota modulation. However, more attention has been paid to the efficacy of soluble dietary fiber than that of insoluble dietary fiber (IDF). In the present study, we investigated whether IDF from barley leaf (BLIDF) can inhibit gut inflammation via modulating the intestinal microbiota in DSS-induced colitis mice. The mice were fed 1.52% BLIDF-supplemented diet for 28 days. Results demonstrated that feeding BLIDF markedly mitigated DSS-induced acute colitis symptoms and down-regulated IL-6, TNF-α, and IL-1β levels in the colon and serum of colitis mice. BLIDF supplementation effectively reduced the abundance of Akkermansia and increased the abundance of Parasutterella, Erysipelatoclostridium, and Alistipes. Importantly, the anti-colitis effects of BLIDF were abolished when the intestinal microbiota was depleted by antibiotics. Furthermore, the targeted microbiota-derived metabolites analysis suggested that BLIDF feeding can reverse the DSS-induced decline of short-chain fatty acids and secondary bile acids in mice feces. Finally, BLIDF supplementation elevated the expression of occludin and mucin2, and decreased the expression of claudin-1 in colons of DSS-treated mice. Overall, our observations suggest that BLIDF exerts anti-inflammatory effects via modulating the intestinal microbiota composition and increasing the production of microbiota-derived metabolites.

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Modulation of the Gut Microbiota by Sihocheonggan-Tang Shapes the Immune Responses of Atopic Dermatitis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.722730 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jaemoo Chun ◽

So Min Lee ◽

You Mee Ahn ◽

Min-Gyung Baek ◽

Hana Yi ◽

...

Keyword(s):

Atopic Dermatitis ◽

Gut Microbiota ◽

Gut Microbiome ◽

Immunoglobulin E ◽

Therapeutic Potential ◽

Interleukin 4 ◽

Hacat Cells ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Ifn Γ

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex immune dysregulation and closely related to the gut microbiome. The present study investigated the microbiome-mediated effect of Sihocheonggan-Tang (SHCGT) on AD-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice. DNCB was applied regularly to the ear and dorsal skin of BALB/c mice, and SHCGT was administered orally daily for 2 weeks. The composition of the gut microbiota was analyzed using 16S rRNA sequencing, and the effect of gut microbiome-derived metabolites, specifically short-chain fatty acids (SCFAs), was evaluated in tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-treated HaCaT cells. SHCGT alleviated DNCB-induced symptoms of AD and the immune response to AD by decreasing the plasma immunoglobulin E level and splenic interleukin-4, interleukin-10, TNF-α, and IFN-γ levels. The gut microbiome composition and the damaged gut epithelial barrier in mice with AD were also significantly altered by SHCGT, and the reduced SCFA levels therein were elevated. We found that SFCAs directly inhibited the mRNA expression of IL-6 and ICAM-1 in TNF-α- and INF-γ-treated HaCaT cells. The finding that SHCGT regulates the gut microbiome and improves DNCB-induced AD in mice suggests that this herbal medicine has therapeutic potential in patients with AD.

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Chitosan Protects Immunosuppressed Mice Against Cryptosporidium parvum Infection Through TLR4/STAT1 Signaling Pathways and Gut Microbiota Modulation

Frontiers in Immunology ◽

10.3389/fimmu.2021.784683 ◽

2022 ◽

Vol 12 ◽

Author(s):

Sajid Ur Rahman ◽

Haiyan Gong ◽

Rongsheng Mi ◽

Yan Huang ◽

Xiangan Han ◽

...

Keyword(s):

Gut Microbiota ◽

Signaling Pathways ◽

Cryptosporidium Parvum ◽

Basal Diet ◽

Sequencing Analysis ◽

Beneficial Effects ◽

Tnf Α ◽

Stat1 Signaling ◽

Ifn Γ ◽

Immunosuppressed Mice

Cryptosporidium parvum infection is very common in infants, immunocompromised patients, or in young ruminants, and chitosan supplementation exhibits beneficial effects against the infection caused by C. parvum. This study investigated whether chitosan supplementation modulates the gut microbiota and mediates the TLR4/STAT1 signaling pathways and related cytokines to attenuate C. parvum infection in immunosuppressed mice. Immunosuppressed C57BL/6 mice were divided into five treatment groups. The unchallenged mice received a basal diet (control), and three groups of mice challenged with 1 × 106 C. parvum received a basal diet, a diet supplemented with 50 mg/kg/day paromomycin, and 1 mg/kg/day chitosan, and unchallenged mice treated with 1 mg/kg/day chitosan. Chitosan supplementation regulated serum biochemical indices and significantly (p < 0.01) reduced C. parvum oocyst excretion in infected mice treated with chitosan compared with the infected mice that received no treatment. Chitosan-fed infected mice showed significantly (p < 0.01) decreased mRNA expression levels of interferon-gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) compared to infected mice that received no treatment. Chitosan significantly inhibited TLR4 and upregulated STAT1 protein expression (p < 0.01) in C. parvum-infected mice. 16S rRNA sequencing analysis revealed that chitosan supplementation increased the relative abundance of Bacteroidetes/Bacteroides, while that of Proteobacteria, Tenericutes, Defferribacteres, and Firmicutes decreased (p < 0.05). Overall, the findings revealed that chitosan supplementation can ameliorate C. parvum infection by remodeling the composition of the gut microbiota of mice, leading to mediated STAT1/TLR4 up- and downregulation and decreased production of IFN-γ and TNF-α, and these changes resulted in better resolution and control of C. parvum infection.

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