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			<p class="Type-of-Article">&nbsp;</p>
			<p class="Type-of-Article"><span class="CharOverride-1">Research Article</span></p>
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			<p class="title- ParaOverride-1">&nbsp;</p>
			<p class="title- ParaOverride-1">Effects of <i>Lactobacillus acidophilus</i> on Pituitary-thyroid Axis in Growing Rat</p>
		</div>
		<div class="Basic-Text-Frame">
			<p class="Authors">&nbsp;</p>
			<p class="Authors"><span class="CharOverride-3">Majida Abdulkhaliq  Jaafar Alqayim</span></p>
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			<p class="Affiliations ParaOverride-1">Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Baghdad, Iraq.</p>
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			<p class="Abstract ParaOverride-1">&nbsp;</p>
			<p class="Abstract ParaOverride-1"><span class="CharOverride-4">Abstract</span> | <span lang="en-US">Several studies have shown that gut microbiota can activate neural pathways and central nervous system signalling systems via gut-brain axis, accordingly the present study was aimed to investigate the interaction of </span><span class="CharOverride-5" lang="en-US">Lactobacillis acidophillus</span><span lang="en-US"> on the activity of pituitary–thyroid axis in the case addressed after weaning of male rats. The study was carried out on growing male rats. At the day of  weaning 12 male kids at age of 30 days were divided into two equal groups and treated as following: 1</span><span class="CharOverride-6" lang="en-US">st</span><span lang="en-US"> group considered as control receiving 1ml of water, 2</span><span class="CharOverride-6" lang="en-US">nd</span><span lang="en-US"> – group received 1ml of MRS (5x10</span><span class="CharOverride-6" lang="en-US">8 </span><span lang="en-US">CFU) of </span><span class="CharOverride-5" lang="en-US">L. acidophilus. </span><span lang="en-US">All the experimental animals were administered orally and daily</span><span class="CharOverride-5" lang="en-US"> </span><span lang="en-US">for the next 32 days. Body weights were recorded at the beginning and end of the experiment. Blood and thyroid gland samples were collected for hormonal assay at the end of the experiment. There was significant differences in body weight gain. Treated group showed less body weight gain than control group. TSH and T3 increased significantly while GH, T4, and TFI were increased slightly in treated group. The analysis of the photomicrograph of thyroid tissue in </span><span class="CharOverride-5" lang="en-US">lactobacillus</span><span lang="en-US"> received group showed increase in the number and size of the thyroid follicles, in addition to a visible hyperchromatic of the follicles epithelia. In conclusion, feeding</span><span class="CharOverride-5" lang="en-US"> </span><span lang="en-US">of</span><span class="CharOverride-5" lang="en-US"> Lactobacillus acidophilus</span><span lang="en-US"> to rat kids showed tangible changes in the pituitary- thyroid axis activity suggesting a positive interaction between </span><span class="CharOverride-5" lang="en-US">Lactobacillus acidophilus</span><span lang="en-US"> and host gut-brain axis. </span></p>
		  <p class="Abstract ParaOverride-1">&nbsp;</p>
			<p class="Abstract ParaOverride-2"><span class="CharOverride-4">Keywords </span>| <span class="CharOverride-5" lang="en-US">Lactobacillus Acidophilus</span><span lang="en-US">, Thyroid gland, gut-brain axis Thyroid hormones, Growth hormone</span></p>
		  <p class="Abstract ParaOverride-2">&nbsp;</p>
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			<p class="Editor----Citation"><span class="CharOverride-4">Editor</span> | Kuldeep Dhama, Indian Veterinary Research Institute, Uttar Pradesh, India.</p>
			<p class="Editor----Citation"><span class="CharOverride-4">Received</span> | March 06, 2015; <span class="CharOverride-4">Revised</span> | March 21, 2015; <span class="CharOverride-4">Accepted </span>| March 22, 2015; <span class="CharOverride-4">Published</span> | April 01, 2015&#9;&#9;</p>
			<p class="Editor----Citation"><span class="CharOverride-4">*Correspondence</span> | Majida Abdulkhaliq Jaafar Alqayim, College of Veterinary Medicine, University of Baghdad, Iraq; <span class="CharOverride-4">Email:</span> jaafer59@yahaoo.com</p>
			<p class="Editor----Citation"><span class="CharOverride-4">Citation</span> | Alqayim MAJ (2015). Effects of <span class="CharOverride-28">Lactobacillus acidophilus</span> on Pituitary-thyroid axis in growing rat. Adv. Anim. Vet. Sci. 3(5): 269-275.  </p>
			<p class="Editor----Citation"><span class="CharOverride-4">DOI </span>| <a href="http://dx.doi.org/10.14737/journal.aavs/2015/3.5.269.275"><span class="Hyperlink">http://dx.doi.org/10.14737/journal.aavs/2015/3.5.269.275</span></a></p>
			<p class="Editor----Citation"><span class="Editor---Citation CharOverride-4">ISSN (Online)</span> | 2307-8316; <span class="Editor---Citation CharOverride-4">ISSN (Print)</span> | 2309-3331</p>
			<p class="Editor----Citation"><span class="CharOverride-4">Copyright</span> © 2015 Alqayim. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
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			<p class="Heading-1--Introduction----">&nbsp;</p>
		  <p class="Heading-1--Introduction----">Introduction</p>
			<p class="Caps-on-First-Para ParaOverride-1">&nbsp;</p>
			<p class="Caps-on-First-Para ParaOverride-1"><span class="_idGenDropcap-1">T</span>hyroid <span class="CharOverride-7">gland is the biggest gland in the neck participate in growth and body’s metabolism. The main function of th</span><span class="CharOverride-8">yroid gland is to synthesis and release the thyroid hormones</span><span class="apple-converted-space CharOverride-8">&#160;</span><span class="Hyperlink CharOverride-8">triiodothyronine</span><span class="apple-converted-space CharOverride-8">&#160;</span><span class="CharOverride-8">(T</span><span class="CharOverride-9">3</span><span class="CharOverride-8">) and its</span><span class="apple-converted-space CharOverride-8">&#160;</span><span class="Hyperlink CharOverride-8">prohormone</span><span class="CharOverride-8">,</span><span class="Hyperlink CharOverride-8">thyroxine</span><span class="apple-converted-space CharOverride-8">&#160;</span><span class="CharOverride-8">(T</span><span class="CharOverride-9">4</span><span class="CharOverride-8">), which is the major form of thyroid hormones in the blood (</span><a href="#Irizarry-L--2014-."><span class="Hyperlink CharOverride-7">Irizarry, 2014</span></a><span class="CharOverride-8">)</span><span class="apple-converted-space CharOverride-8">. The thyroid hormones exert many physiological functions act on most of the body’s cells, increase basal metabolic rate, effect on protein, fat, and carbohydrates metabolism (</span><a href="#Gelfand-RA--Hutchinson-Williams-KA--Bonde-AA--Castellino-P--Sherwin-RS--1987"><span class="Hyperlink CharOverride-7">Gelfand et al., 1987</span></a><span class="apple-converted-space CharOverride-8">). During fetal life thyroid hormones are synthesized and released from the fetus under pituitary control through </span><span class="Hyperlink CharOverride-8">thyroid-stimulating hormone</span><span class="apple-converted-space CharOverride-8">&#160;</span><span class="CharOverride-8">(TSH). TSH secretion from fetal pituitary is evident by 12</span><span class="apple-converted-space CharOverride-8">&#160;</span><span class="Hyperlink CharOverride-8">weeks of gestation</span><span class="CharOverride-8">, and fetal production of</span><span class="apple-converted-space CharOverride-8">&#160;</span><span class="Hyperlink CharOverride-8">thyroxine</span><span class="apple-converted-space CharOverride-8">&#160;</span><span class="CharOverride-8">(T</span><span class="CharOverride-9">4</span><span class="CharOverride-8">) reaches a clinically significant level at 18-20 weeks.</span></p>
		  <p class="Caps-on-First-Para ParaOverride-1">&nbsp;</p>
			<p class="Body-Text">The periventicular neurons in the hypothalamus (PVN) synthesize and release thyrotropin-releasing hormone that stimulate the release of thyroid-stimulating hormone from the pituitary, and TSH stimulate the synthesis and release of T4 from thyroid, this what called the hypothalamus-pituitary- thyroid (HPT) axis (<a href="#Puymirat-J--1992"><span class="Hyperlink">Puymirat, 1992</span></a>). Regulation of HPT mediated by a negative feedback effects through thyroid hormone receptors in the pituitary and hypothalamus (<a href="#Scanlon-M--1992"><span class="Hyperlink">Scanlon, 1992</span></a>; <a href="#Morley-J--1981-."><span class="Hyperlink">Morley, 1981</span></a>). During the maternal life the thyroid gland activity, like another tissues influenced with maternal environment, but in postnatal life in spite to the master pacemaker in the brain, it influence by local independent circadian oscillators, which is mostly affected by postnatal development (<span class="Hyperlink">Yamazaki</span><a href="#Yamazaki-S--Yoshikawa-T--Biscoe-EW--Numano"><span class="Hyperlink"> et al., 2009</span></a>). Although the molecular mechanism of the circadian regulation of the hypothalamus-pituitary-thyroid axis (<span class="Hyperlink CharOverride-11">HPT</span>) not yet analyzed, but it well - known that this <span class="Hyperlink CharOverride-11">HPT</span> axis rhythms, are tightly regulated by the circadian system (<a href="#Jacques-P--Charna-D--2014"><span class="Hyperlink">Jacques, 2014</span></a>).</p>
		  <p class="Body-Text">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">Gastrointestinal tract is regulated by two neural circuits and their interaction. The autonomic sympathetic and para sympathetic system on the one hand and enteric nervous system (ENS) on the other hand  regulates most aspects of GI physiology, which constitutes a relay station in the bi-directional neuro-endocrine pathways that connect the digestive system and the brain (gut-brain axis) (<a href="#Collins-R--Surette-M--Bercik-P--2012"><span class="Hyperlink">Collins et&#160;al., 2012</span></a>). Enteric microbiota are essential for the developing ENS during the postnatal life in different regions of the intestine (<a href="#Collins-R--Borojevic-EF--Verdu-JD--Huizinga-EM--Ratcliffe--2014"><span class="Hyperlink">Collins et al., 2014</span></a>). Strong new evidences suggest the interference of gut microbiota with gastrointestinal microenvironment regulation and host behavior and brain chemistry. Accordingly it has been found that commensal and probiotics in the gastrointestinal tract can activate neural pathways and central nervous system signaling (<a href="#Foster-JA---Mcvey-Neufeld-KA--2013"><span class="Hyperlink">Foster and Mcvey, 2013</span></a>; <a href="#Bercik-P--Collins-SM--2014"><span class="Hyperlink">Bercik and Collins, 2014</span></a>). <a href="#Lyer-LM--Aravind-L--Coon-SL--Klein-DC--Koonin-EV--2004"><span class="Hyperlink">Lyer et al. (2004)</span></a> stated that gut micro biota can produce neurochemicals are exactly the same found in the host tissues and with same pathways. Based on previous reports (<a href="#Lyte-M--2011"><span class="Hyperlink">Lyte, 2011</span></a>), <span class="CharOverride-5">Lactobacillus </span>have revealed high concentrations of intracellular neurochemicals such as GABA. These observations arise the possibility of the microbiota- gut-brain inter action is the mechanism by which the microbiota may influence host behavior (<a href="#Lyte-M--2014"><span class="Hyperlink">Lyte, 2014</span></a>). Gut micro biota might regulate brain-gut axis through many postulated mechanisms one of the most accepted that through regulation of, serotonin synthesis as serotonin the key neurotransmitter in the both terminal of brain- gut axis (<a href="#Mahony-SMG--Clarke-YE--Borre-TG--Dinan--JF--Cryan--2015"><span class="Hyperlink">Mahony et al., 2015</span></a>), furthermore, pyrroloquinoline quinone producing probiotics in rat intestine modulate gut-brain axis by restored neurotransmitter levels (<a href="#Pandey-S--Ashish-S---Nirja-C--Laximpriya-P--Nampoothiri-G--Naresh-K--2015"><span class="Hyperlink">Pandey et al., 2015</span></a>). At the level of interference with thyroid gland activity specifically, mixed treatment of 2 strains of <span class="CharOverride-5">Lactobacillus</span> with phytosterol-containing treatments induced the increased activity of thyroid glands, as evident by elevated levels of serum total thyroxine, total triiodothyronine, and free triiodothyronine (<a href="#Awaisheh--SS--Khalifeh--MS--Al-Ruwaili-MA--Khalil-OM--Al-Ameri-OH--Al-Groom-R--2013"><span class="Hyperlink">Awaisheh et al., 2012</span></a>).<span class="CharOverride-5"> Lactobacillus acidophilus</span>, is a lactic acid producing bacteria it is gram positive, non-spore forming cocci, cocco- bacilli or rods in most cases they are anaerobic, they need fermentable carbohydrates for growth and for the production of lactic acid (<a href="#Cotter-PD--Rose-HC--2005"><span class="Hyperlink">Cotter and Rose, 2005</span></a>). Some strains of<span class="CharOverride-5"> L. acidophilus</span> considered to have probiotic characteristics that has the potential to protect the oxidative damage mediated by the reactive oxygen species and can act as antioxidative probiotic (<a href="#Deeplina-D--Arun-G--2015"><span class="Hyperlink">Deeplina and Arun, 2015</span></a>) and promote health benefits (<a href="#Usman-M--2014"><span class="Hyperlink">Usman, 2014</span></a><span class="CharOverride-12" lang="en-US">; </span><a href="#Alqayim-MAJ--Abass-DE--2014-"><span class="Hyperlink" lang="en-US">Alqayim and Abass, 2014</span></a>). Thyroid gland function influence health care for example hypothyroidism may also lead to congestive heart failure due to the increased systemic vascular resistance and decreased cardiac contractility. For the purpose of shedding light on side of the interaction of gut microbiota with gut-brain axis, the present study was aimed to investigate the interaction of <span class="CharOverride-5">L. acidophillus</span> on the  activity of pituitary –thyroid axis in the case addressed after weaning of male rats. </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Body-Text ParaOverride-1"><span class="CharOverride-13">Material and Methods</span></p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">Experimental Animal and Diet</p>
			<p class="Body-Text">Ten healthy Albino Wister pregnant female rats, were kept under suitable condition of (21-25°C) in an air condition room, and were fed freely with standard pellet diet (<a href="#Table-1-"><span class="Hyperlink">Table 1</span></a>). At the day of parturition each dam isolated in a single cage. After parturition these dams with their kids were kept under suitable condition and well fed until day of weaning. At weaning time, 6 male kids from each group were chosen, isolated and placed in a another cages to treated as follow: 1<span class="CharOverride-6">st</span> control group kept on distil water 2<span class="CharOverride-6">nd</span> group began to received (5 × 10<span class="CharOverride-6">8</span> CFU) of <span class="CharOverride-5">Lactobacillus acidophilus. </span>This treatment continued for another 32 days. Body weight (gm) were recorded at the time of weaning and after 32 days, at the end of experiment for calculation of body weight gain. At the end of the experiment all the experimental animals were anesthetized by intraperitoneal injection with 35 mg/kg ketamine hydrochloride. After opening the chest cavity, blood was collected by acupuncture through the left ventricle for hormonal assay. Thyroid gland were isolated and dried with filter paper and weighted, then preserved in formalin solution for histological examination.</p>
		  <p class="Body-Text">&nbsp;</p>
			<p class="Figure--and-Table-Heading ParaOverride-1"><span class="CharOverride-4"><a id="Table-1-"></a>Table 1: </span>Experimental diet</p>
			<table width="657" height="324" class="Table-Style-1" id="table-1">
				<colgroup>
					<col class="_idGenTableRowColumn-1" />
					<col class="_idGenTableRowColumn-2" />
				</colgroup>
				<tbody>
					<tr class="_idGenTableRowColumn-3">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-16">Percentage</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-16">Nutrient Composition</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-4">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">88% </span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Dry matter</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-3">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">14-16%</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Crude protein</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-4">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">2.5-3.0%</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Crude fat</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-3">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">2.5-3.0%</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Crude fiber</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-4">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">10% </span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Crude Ash</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-3">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">10%</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Moisture</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-4">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">1-3%</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Calcium</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-3">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">1%</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Phosphorus</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-4">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">1%</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">NaCl</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-3">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">5000 IU/KG</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Vitamin A</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-4">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">700IU/KG</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Vitamin D3</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-3">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">30 mg/KG</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Vitamin E</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-4">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">2400 Kcal/KG</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">Metabolizable Energy</span></p>
						</td>
					</tr>
				</tbody>
			</table>
			<p class="Heading-2--History-in-MM-">&nbsp;</p>
		  <p class="Heading-2--History-in-MM-">Serum Hormonal Assay</p>
			<p class="Body-Text ParaOverride-1">Serum T3, T4, TSH, and GH were measured by radioimmunoenzymetric assay using commercial kits supplied from Accu-bind Monobind –USA. </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">Thyroid Function Index (TFI)</p>
			<p class="Body-Text ParaOverride-1">The TFI is an index for the clinical evaluation of thyroid function described by (<a href="#Mamtani-M--Kulkarni-H--Dyer-TD--Almasy-2014"><span class="Hyperlink">Mamtani et al., 2014</span></a>). Depending on the calculated value of TFI in control group, we can distinguish whether there is a hyperthyroidism or hypothyroidism TFI<img class="_idGenPageitem-1" src="AAVS_MH20150306200334_-Alqayim-web-resources/image/Image15913530.png" alt=" " />=<img class="_idGenPageitem-1" src="AAVS_MH20150306200334_-Alqayim-web-resources/image/Image15913533.png" alt=" " />TSH/ (FT3 × FT4).</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">Histological Analysis</p>
			<p class="Body-Text ParaOverride-1">Sections of the thyroid gland were obtained from the experimental groups and were fixed with 10% for histopathological evaluation. Serial sections were prepared as described in (<a href="#Luna-LG--1968-"><span class="Hyperlink">Luna, 1968</span></a>).</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">Statistical Analysis</p>
			<p class="Body-Text ParaOverride-1">The Statistical Analysis System- <a href="#Sas--2012"><span class="Hyperlink">SAS (2012)</span></a> was used to analyze effect of different factors in study parameters. Least significant difference –LSD test was used to significant compare between means in this study. </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction----">Results</p>
		  <p class="Heading-1--Introduction----">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">Thyroid Weight and Body Weight Gain </p>
			<p class="Body-Text ParaOverride-1">Results shown in <a href="#Figure-1-"><span class="Hyperlink">Figure 1</span></a> revealed that there were significant differences in body weight gain between groups. The greatest body weight gain recorded in the present study was in control group, in addition feeding <span class="CharOverride-5">L. acidophilus </span>to growing rats did not increase body weight in the present study. </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			
            <div class="pt" > <a href="http://nexusacademicpublishers.com/uploads/figures/20150403032630.png" target="new"><img class="img_display" src="http://nexusacademicpublishers.com/uploads/figures/20150403032630.png" width="80" height="80"></a>
            
        <p class="Figure--and-Table-Heading ParaOverride-1"><span class="CharOverride-4"><a id="Figure-1-"></a>Figure 1: </span> <a href="http://nexusacademicpublishers.com/uploads/figures/20150403032630.png">Effects of<span class="CharOverride-5"> L. acidophilus</span> on body weight gain (gm) during the 32 days post weaning</a></p>
       </div><br>

			
			<div class="pt" > <a href="http://nexusacademicpublishers.com/uploads/figures/20150403030131.png" target="new"><img class="img_display" src="http://nexusacademicpublishers.com/uploads/figures/20150403030131.png" width="80" height="80"></a>
            
      <p class="Figure--and-Table-Heading ParaOverride-1"><span class="CharOverride-4"><a id="Figure-2-"></a>Figure 2: </span> <a href="http://nexusacademicpublishers.com/uploads/figures/20150403030131.png">Effects of feeding <span class="CharOverride-5">L. aciaophilus</span> on Thyroid Function Index (TFI) during the 32 day spot weaning</a></p>
       </div><br>
			
		  <p class="Heading-2--History-in-MM-">Pituitary-thyroid Axis</p>
			<p class="Body-Text ParaOverride-1">Results of the present study shown in <a href="#Table-2-"><span class="Hyperlink">Table 2</span></a> represent the differences in GH, TSH, T4, and T3 in the serum of the different experimental rats. Results reveled a significant (P&lt;0.05) elevation in TSH and T3 and non-significant in GH and T4 in rats kids fed <span class="CharOverride-5">Lactobacillus acidophilus </span>for 32 days post weaning when compare with control. When the TFI account showing the existences of differences in rats had fed<span class="CharOverride-5"> L. acidophilus</span> in comparison with control group as shown in <a href="#Figure-2-"><span class="Hyperlink">Figure 2</span></a>, the non-significant TFI increase in 2<span class="CharOverride-6">nd</span> group suggesting a functional hyperthyroidism. </p>
			<p class="Figure--and-Table-Heading ParaOverride-1">&nbsp;</p>
			<p class="Figure--and-Table-Heading ParaOverride-1"><span class="CharOverride-4"><a id="Table-2-"></a>Table 2:</span> Effects of feeding<span class="CharOverride-5"> L. acidophilus</span> on GH, TSH, T4, and T3 for 32 days post weaning in male rats</p>
			<table width="657" height="94" class="Table-Style-1" id="table-2">
				<colgroup>
					<col class="_idGenTableRowColumn-5" />
					<col class="_idGenTableRowColumn-6" />
					<col class="_idGenTableRowColumn-7" />
					<col class="_idGenTableRowColumn-6" />
					<col class="_idGenTableRowColumn-8" />
				</colgroup>
				<tbody>
					<tr class="_idGenTableRowColumn-9">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-16">Animal groups</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-16">GH</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-16">TSH</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-16">T4</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-16">T3</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-10">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">1</span><span class="CharOverride-19">st</span><span class="CharOverride-17">control</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">0.923 ± 0.05</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">1.48 ± 0.04</span><span class="CharOverride-19">b</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">2.46 ± 0.23</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">1.26 ± 0.03</span><span class="CharOverride-19">c</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-11">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">2</span><span class="CharOverride-19">nd</span><span class="CharOverride-17"> group </span><span class="CharOverride-20">lactobacillus</span><span class="CharOverride-17"> (5 × 10</span><span class="CharOverride-19">8</span><span class="CharOverride-17"> CFU)</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">1.08 ± 0.08</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">2.27 ± 0.28</span><span class="CharOverride-19">a</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">2.88 ± 0.23</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">1.65 ± 0.07</span><span class="CharOverride-19">a</span></p>
						</td>
					</tr>
					<tr class="_idGenTableRowColumn-12">
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">LSD value</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">0.194 NS</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">0.514 *</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">0.744 NS</span></p>
						</td>
						<td>
							<p class="Basic-Paragraph"><span class="CharOverride-17">0.142 *</span></p>
						</td>
					</tr>
				</tbody>
			</table>
			<p class="Figure--and-Table-Heading ParaOverride-1">&nbsp;</p>
		  <p class="Figure--and-Table-Heading ParaOverride-1"><span class="CharOverride-10">* (P≤0.05); (mean ± SE); n=6</span></p>
			<p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">The relationship between serum TSH and thyroid weight in rats fed <span class="CharOverride-5">L. acidophilus</span> for 32 days shown in <a href="#Figure-3-"><span class="Hyperlink">Figure 3</span></a>. The R<span class="CharOverride-6">2</span> value (0.503) show significant regression of variable of y on variation of x values. The histological examination of thyroid gland sections from control and <span class="CharOverride-5">L. acidophilus</span> administered groups were presented in <a href="#Figure-3-"><span class="Hyperlink">Figure 3</span></a>. </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
              <p class="Body-Text ParaOverride-1">The analysis of the thyroid light microscopic photomicrograph obtained from control group (<a href="#Figure-4-"><span class="Hyperlink">Figure 4</span></a>) reveled a normal size and number of follicles lined by squamous to cuboidal shape follicular cells and filled with light to moderate colloid material. Thyroid sections from 2<span class="CharOverride-6">nd</span> group that fed with <span class="CharOverride-5">L. acidophilus</span> (<a href="#Figure-5-"><span class="Hyperlink">Figure 5</span></a>) showed that there were two types of follicles some of them are widely distended and filled with well stained colloidal material lined by hyper plastic squamous epithelia, also there were the finger like projection indicating a the hyperplasia of flat epithelial cells. In addition there were another type of small follicles filled with tense colloid material and lined by clear cuboidal epithelial cells characterized by a visible basophilic hyperchromatic, other section showed a vacuolar changes in the peripheral regions of the follicles epithelial.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			
            <div class="pt" > <a href="http://nexusacademicpublishers.com/uploads/figures/20150403035431.png" target="new"><img class="img_display" src="http://nexusacademicpublishers.com/uploads/figures/20150403035431.png" width="80" height="80"></a>
            
      <p class="Figure--and-Table-Heading ParaOverride-1"><span class="CharOverride-4"><a id="Figure-3-"></a>Figure 3: </span> <a href="http://nexusacademicpublishers.com/uploads/figures/20150403035431.png">Relationship between serum TSH and thyroid weight in rats fed <span class="CharOverride-5">L. acidophilus</span> for 32 days. The R<span class="CharOverride-6">2</span> value show significant regression of variable of y on variation of x values</a></p>
       </div><br>
			
		
			
            <div class="pt" > <a href="http://nexusacademicpublishers.com/uploads/figures/20150403030333.png" target="new"><img class="img_display" src="http://nexusacademicpublishers.com/uploads/figures/20150403030333.png" width="80" height="80"></a>
            
    <p class="Figure--and-Table-Heading ParaOverride-1"><span class="CharOverride-4"><a id="Figure-4-"></a>Figure 4: </span><a href="http://nexusacademicpublishers.com/uploads/figures/20150403030333.png">Light microscopic photograph of thyroid gland in control group (A-10x, B-40x). It shows a normal size and number of follicles lined by squamous to cuboidal shape follicular cells and filled with light to moderate colloid material (H&amp;E)</a></p>
       </div>
            <p>&nbsp;</p>
          <p><br>
              
            </p>
          <p class="Heading-1--Introduction----">Discussion</p>
          <p class="Heading-1--Introduction----">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">Body Weight Gain</p>
			<p class="Body-Text ParaOverride-1">Gut micro biota feeding play a significant role in regulation of energy balance of the host, one of the postulated mechanism for this regulation defined by <a href="#Turnbaugh-PJ--Ley-RE--Mahowald-MA--Magrini-V--Mardis-ER--Gordonji--2006"><span class="Hyperlink">Turnbaugh et al. (2006</span></a><span class="Hyperlink">)</span>, suggesting a metabolic pathway in food energy extraction. On the other hand dietary inclusion with different strains of <span class="CharOverride-5">Lactobacillus</span> was potential and safer anti- obesity natural bioactive material (<a href="#Torres-Fuentes-C--Schellekens-H--Dinan-TG--Cryan-JF--2015"><span class="Hyperlink">Torres et al., 2015</span></a>). Based on the above, the results of weight gain in the present study suggest an active role for <span class="CharOverride-5">L. acidophilus</span> as anti-obesity bioactive material. In spite of the reduced body weight gain in the <span class="CharOverride-5">L. acidophilus</span> fed rat there was increase in thyroid weight /body weight, which indicate increase of thyroid growth. </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			
			
            <div class="pt" > <a href="http://nexusacademicpublishers.com/uploads/figures/20150403031734.png" target="new"><img class="img_display" src="http://nexusacademicpublishers.com/uploads/figures/20150403031734.png" width="80" height="80"></a>
            
    <p class="Figure--and-Table-Heading ParaOverride-1"><span class="CharOverride-4"><a id="Figure-5-"></a>Figure 5: </span> <a href="http://nexusacademicpublishers.com/uploads/figures/20150403031734.png">Light microscopic photograph of thyroid gland in <span class="CharOverride-5">L. acidophilus</span> group (A-10x, B-40x). Show widely distended and filled with well stained colloidal material lined by hyper plastic, basophilic hyper chromatic epithelia, (H&amp;E)</a></p>
       </div><br>
			
		 <p class="Heading-2--History-in-MM-">Pituitary –Thyroid Axis</p>
			<p class="Body-Text ParaOverride-1">In the present study<span class="CharOverride-4"> </span>the significant increase in serum TSH indicate a coordinator role for <span class="CharOverride-5">L. acidophilus </span>on the brain –pituitary –thyroid axis. In spite of regulation of gastrointestinal physiology, the enteric nervous system or what called the little brain, also modulate communication between the gut and central nervous system (<a href="#Sharma-A--Lelic-D--Brock-C--Paine-P--Aziz-Q--2009"><span class="Hyperlink">Sharma et al., 2009</span></a>). The coordination between the brain, the intesti nal tract and endocrine systems is well described (<a href="#Mayer-E--2011"><span class="Hyperlink">Mayer, 2011</span></a>). The enterochromaffin cells in the lamina propria work as a bidirectional transducer between nervous system and gut lumen (<a href="#Rhee-SH--Charalabos-P--Emeran-AM--2009"><span class="Hyperlink">Rhee et al., 2009</span></a>). Body of recent evidences discuss the role of probiotics  in the organization of this brain-gut axis and modulating of endocrine system (<a href="#Cryan-JF--Dinan-TG--2015-"><span class="Hyperlink" lang="en-US">Cryan and Dinan</span><span class="Hyperlink">, 2015</span></a>; <a href="#Hemarajata-P--Versalovic-J--2013-"><span class="Hyperlink" lang="en-US">Hemarajata and Versalovic</span><span class="Hyperlink">, 2013</span></a>; <a href="#Pandey-S--Ashish-S---Nirja-C--Laximpriya-P--Nampoothiri-G--Naresh-K--2015"><span class="Hyperlink">Pandey et al., 2015</span></a>). The high level of TSH and GH denoted in the present study encourage the suggestion that the <span class="CharOverride-5">L. acidophilus</span> used in this trial instrumental in organization the pituitary gland. A close relationship between thyrotropin-releasing hormone (THR), thyroid stimulating hormone (TSH), and growth hormone (GH) had been found and this axis plays an important role in growth (<a href="#Cogburn-LA--Mao-NC--Agrawal-S--Burnside-J--1995"><span class="Hyperlink">Coghurn et al., 1995</span></a>).<span class="CharOverride-5"> </span>Normally<span class="apple-converted-space CharOverride-7">&#160;</span>the activity of hypophysiotropic <span class="Hyperlink CharOverride-11">TRH</span><span class="apple-converted-space CharOverride-7">&#160;</span>neurons is regulated by the negative feedback effects of thyroid hormone to ensure stable, circulating, thyroid hormone concentrations, but in the current experiment, observed persistence of high TSH despite rising T3in the circulationthis may be explained by the occurrence alteration in the set point for negative feedback regulation by thyroid hormones. </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">Organisms adapted to changing in environmental conditions via different mechanisms, one of these is the thyroid axis mediating suppression of Hypophysiotropic<span class="apple-converted-space CharOverride-7">&#160;</span><span class="Hyperlink CharOverride-11">TRH</span><span class="apple-converted-space CharOverride-7">&#160;</span>neurons (<a href="#Fekete-C--Lechan-RM--2014-."><span class="Hyperlink">Fekete and Lechan, 2014</span></a>). Raising of TSH induce effects on thyroid gland and increase in the synthesis and release of thyroid hormones, T4 and T3. But in the present study the significant increase in T3 at the expense of T4 in 3<span class="CharOverride-6">rd</span> and 2<span class="CharOverride-6">nd</span> groups leads us to the assumption that there were increasing in the conversion of blood circulation T4 to the active T3. T4 converted to T3 within<span class="apple-converted-space CharOverride-7">&#160;</span><span class="Hyperlink CharOverride-11">cells</span><span class="apple-converted-space CharOverride-7">&#160;</span>by<span class="apple-converted-space CharOverride-7">&#160;</span><span class="Hyperlink CharOverride-11">deiodinases</span><span class="apple-converted-space CharOverride-7">&#160;</span>(5’-iodinase), in thyroid and liver , and kidney tissues, but the liver is the major tissue for this conversion .Among the factors that inhibits the liver conversion of T4 to T3 is the presence of free radical load (<a href="#Marit-ME--Van-Bakel--Gert-Printzen--Bendicht-Wermuth--Ulrich-N-Wiesmann--2000-"><span class="Hyperlink">Marit et al., 2000</span></a>; <a href="#Vadhanavikit-S--Ganther-H--1993"><span class="Hyperlink">Vadhanavikit and Ganther, 1993</span></a>). The thyroid gland is a unique endocrine gland that requires hydrogen peroxide for thyroid hormone synthesis. Oxidative reactions in thyroid gland are predisposing for thyroid hormones synthesis correlated with production of ROS particularly H2O2 under physiological conditions (<a href="#Kale-MK--2015-."><span class="Hyperlink">Kale, 2015</span></a>). Thyroid gland contain a defined H2O2 generating system, this H2O2 is required as a substrate control the thyroperoxidase, the enzyme catalyzes the Iodide-protein binding during the thyroid hormones synthesis (<a href="#Corvilain-B--Van-Sande-J--Laurent-E--Dumont-JE--1991-"><span class="Hyperlink">Corvilain et al., 1991</span></a>). Thyroid epithelial cells are well adapted to endogenously produced ROS in basal and goitrous conditions (<a href="#Jacob-JJ--Stephen-C--Paul-TV--Thomas-N--Oommen-R--Seshadri-MS--2015"><span class="Hyperlink">Jacobet al., 2015</span></a>). Using antioxidants in improving thyroid gland function were studied (<a href="#Karan-P1--Deshpande-U--Choudhary-PS--2014"><span class="Hyperlink">Karan et al., 2014</span></a>). Reducing lipid peroxidation and protecting the liver from oxidative effects of free radicals will be one of the main strategies to promote conversion of T4 to T3 by using herbs (<a href="#Sage-K--2013-"><span class="Hyperlink" lang="en-US">Sage</span><span class="Hyperlink">, 2013</span></a>). Meanwhile <span class="CharOverride-5">L. acidophilus</span> proved its effectiveness as antioxidant (<a href="#Abu-Elsaad-NM--Adb-Elhameed-AG--El-karef-A--Ibrahim-TM--2015"><span class="Hyperlink">Abu-Elsaad et al., 2015</span></a>) this has resulted in appositive way to increase the conversion of T4 to T3 in the present experiment. Same results recorded by (<a href="#Chenhui-LV--Taiji-W--Shengfa-FL--Kehe-H--2014-"><span class="Hyperlink">Chenhui et al., 2014</span></a>) who found that feeding Se-probiotics caused increase in T3 and not T4. </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Body-Text">The histological examination of the thyroid gland revealed that the probiotic-fed rats in the present study have increase of follicular number and follicular cell hyperplasia (increased cell number) and follicular cell hypertrophy (increased cell size) as well as reduces size and become more regularly- shaped ,dense colloid space. Changes observed in thyroid tissue of rats fed with <span class="CharOverride-5">L. acidophilus</span> that indicate increase in thyroid hyperplasia and activity specifically the finger like projection and the peripheral of the vacuolated follicles which considered a signed of active resorption. By contrast the appearance of proliferative epithelial of small follicles filled with tens colloid product could explain the <span class="CharOverride-5">L.acdiophilus</span> –associated increase in T4 and T3in the present study. These findings are signs of thyroid activity may be resulted from the hypersensitivity of the thyroid to increased TSH denoted in the present study. As the TSH considered the major regulating factor for thyroid growth (<a href="#Rapoport-B--Spaulding-SW--1996"><span class="Hyperlink">Rapoport and Spaulding, 1996</span></a>), results confirmed this correlation as mention by the R2 values, the same pattern of thyroid response to probiotic was recorded by (<a href="#Hood-A--Ya-Ping-L--Vincent-H--Gattone-Ii--Curtis-DK--1999"><span class="Hyperlink">Hood et al., 1999</span></a>), who found that moderate increase in serum TSH resulted in increased number of proliferating thyroid follicles. Furthermore <span class="CharOverride-5">Lactobacillus</span> other species supplementation improved thyroid function (<a href="#Bernard-JV--Theofilos-P--Tatiana-L--Yassin-MI--2014"><span class="Hyperlink">Bernard et al., 2014</span></a>). </p>
		  <p class="Body-Text">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">In conclusion, the present finding suggest a significant role of feeding probiotic(<span class="CharOverride-5">Lactobacillus-acidophilus</span>) in regulation of the brain-gut axis resulting in increase of pituitary –thyroid axis activity ,thyroid sensitivity to TSH. It is concluded from the increase in thyroid activity associated with no increase in body weight gain that probiotis feeding in one way or another modifying metabolic rate, to make sure of this we suggest further studies concerned with. </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction----">Acknowledgment</p>
		  <p class="Heading-1--Introduction----">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">The authors would like to express their deep gratitude and appreciations to Dr. Anaam Badder for her help in the analysis and description of the histological part of this research.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction----">References </p>
		  <p class="Heading-1--Introduction----">&nbsp;</p>
			
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